This phase III trial compares standard therapy given after surgery (adjuvant) to standard therapy given before and after surgery (perioperative) in treating patients with stage II-IIIB non-small cell lung cancer (NSCLC) that can be removed by surgery (resectable). The usual approach for patients with resectable NSCLC is chemotherapy and/or immunotherapy before surgery, after surgery, or both before and after surgery. This study is being done to find out which approach is better at treating patients with lung cancer. Treatment will be administered according to the current standard of care at the time of enrollment. Chemotherapy options may include cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and vinorelbine at standard doses according to the treating physician. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid (DNA) and may kill tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Other chemotherapy drugs, such as vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading . Immunotherapy with monoclonal antibodies, such as nivolumab, pembrolizumab, and atezolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with chemotherapy and immunotherapy prior to surgery and continuing treatment after surgery may be a more effective treatment option than adjuvant therapy alone in patients with stage II-IIIB resectable NSCLC.

Start Date30 May 2025

Sponsor / Collaborator

Alliance for Clinical Trials in Oncology

[+1]

NCT04595981 / Not yet recruitingPhase 2IIT

Chemo-embolization for Head and Neck Cancer

The study will evaluate whether adjuvant chemo-embolization increases progression free and/or overall survival relative to standard of care radiation and chemo- and/or immunotherapy in cisplatin-ineligible head and neck cancer patients with an acceptable morbidity rate.

Start Date01 May 2025

Sponsor / Collaborator

The University of Alabama at Birmingham

NCT05570422 / Not yet recruitingPhase 1

A Phase 1/2 Study to Evaluate the Safety, Tolerability, Preliminary Efficacy of KRC-01 Intratumoral Injection Combined With Radiotherapy in Patients With Locally Advanced Cervical Cancer

This is a seamless Phase 1/2 study consisting of two components. Phase 1 component is a dose-escalation, single arm, open label study in 10 patients to evaluate the safety and tolerability of KRC 01. Phase 2 component is a randomized, open label, controlled, multi-center study in 60 patients to evaluate the preliminary antitumor effect of KRC-01 in combination with CRT.

Start Date01 Apr 2025

Sponsor / Collaborator

KORTUC, Inc.Startup

100 Clinical Results associated with Cisplatin

100 Translational Medicine associated with Cisplatin

100 Patents (Medical) associated with Cisplatin

77,353

Literatures (Medical) associated with Cisplatin

01 Dec 2025·Journal of Gastrointestinal Cancer

Impact of Retroperitoneal Lymphadenopathy (RPLN) on the Outcomes of Locally Advanced Gall Bladder Cancer (GBC) Following Chemotherapy (CT) or Chemotherapy Followed by Consolidation Chemoradiotherapy (CTRT)

Article

Author: Naik, Nagendra ; Priyanka, Parul ; Agrawal, Sushma

INTRODUCTION:

Retroperitoneal lymphadenopathy is considered a metastatic disease in GBC; however, some surgical series of radical surgery with enlarged RPLN who underwent RPLN dissection have shown results marginally inferior to those without enlarged RPLN. Radiological RPLN comprises a major proportion of advanced non-metastatic GBC. There is dilemma in the intent of treatment to be offered in such cases. We are reporting our series of outcome of GBC with RPLN treated with first-line CT followed by consolidation CTRT.

MATERIALS AND METHODS:

Non-metastatic locally advanced GBC with good performance status (KPS ≥ 80) were initiated on first-line CT (cisplatin-gemcitabine), and thereafter, responders were evaluated by CECT-angiography and PET-CT scan for resectability. If found unresectable, they were offered consolidation CTRT to a dose of 45 Gy by conventional fractionation (3D-CRT technique) along with concurrent capecitabine at 1250 mg/m² to GBC and regional lymphatics including RPLN. Thereafter, boost dose of 9 Gy/5# was given to GBC only. Response assessment was done using CECT abdomen by RECIST criteria v 1.1. Outcomes (overall survival) of the two groups (RPLN vs non-RPLN) were computed with Kaplan-Meier survival curves and chi-square tests using SPSS v 20.

RESULTS:

Among 189 patients of advanced non-metastatic GBC recruited from 2011 to 2022, 80 had RPLN. The demographic features of both groups were comparable. Overall, 68% of the patients were women, 30% underwent upfront stenting for obstructive jaundice, and 90% had T3 and T4 disease. Only 10% had undergone upfront laparoscopic staging and had pathologically proven RPLN. Forty percent of the patients received four cycles of CT only and 50% of the patients received six cycles or more and 33% received CTRT. By RECIST criteria, 10% vs 16% achieved complete response (CR), 39% vs 41% achieved partial response (PR), 16% vs 15% achieved stable disease (SD), 2.7% vs 6% had disease progression (PD), and 14.5% vs 3.7% were non-evaluable in non-RPLN group vs RPLN group, respectively. 12% vs 6% could undergo radical surgery in non-RPLN group vs RPLN group (p = 0.03). The median OS was 9 months (95% CI 7.6-10.3 months) vs 10 months (95% CI 8-9.8 months) (p = NS) in non-RPLN group vs RPLN group, respectively. In those who received CT only, the median OS was 7 months vs 8 months, while in those who received CT followed by CTRT, the median OS was 14 months vs 13 months (p = 0.65) in non-RPLN group vs RPLN group, respectively.

CONCLUSIONS:

Based on this analysis, we conclude that RPLN constitutes a major proportion of advanced non-metastatic GBC and has outcomes similar to those without RPLN if treated with radical intent. RPLN should not be considered a metastatic disease and should be treated with radical intent.

01 Dec 2025·Journal of Gastrointestinal Cancer

Network Meta-analysis of Randomized Controlled Trials in Patients with Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer: Comparisons Involving Ramucirumab

Review

Author: Taipale, Kaisa ; Paine, Abby ; Gupta, Palvi ; D'yachkova, Yulia ; Liepa, Astra M ; Earley-Valovic, Veronika ; Goel, Rajat

PURPOSE:

With relatively few direct comparisons among treatment options for previously treated advanced gastric cancer or gastroesophageal junction (GEJ) cancer, network meta-analysis (NMA) may inform evidence-based decision-making. Ramucirumab plus paclitaxel (RAM + PTX) is a preferred regimen in guideline recommendations. NMA of key outcomes may further characterize the relative clinical value of RAM + PTX.

METHODS:

A systematic literature review of randomized controlled trials of adult patients with previously treated advanced gastric/GEJ cancer informed a NMA which compared overall survival, progression-free survival, and discontinuations due to adverse events. Comparisons were reported relative to placebo/best supportive care (BSC) when possible, otherwise relative to RAM + PTX.

RESULTS:

The base-case NMA focused on second-line treatment only, from 19 of 28 studies identified. For overall survival, seven of 16 regimens were favorable relative to placebo/BSC, with RAM + PTX as the most favorable. For progression-free survival, five of 14 regimens were unfavorable relative to RAM + PTX. For discontinuations due to adverse events, two of 13 regimens were similar to placebo/BSC: ramucirumab monotherapy and fluorouracil; relative to RAM-PTX, all regimens were similar except ramucirumab monotherapy which was favorable and irinotecan + cisplatin which was unfavorable.

CONCLUSION:

This NMA of trials of previously treated gastric/GEJ cancer suggests that RAM + PTX has one of the more favorable clinical profiles.

01 Mar 2025·BIOMATERIALS

Cell calcification reverses the chemoresistance of cancer cells via the conversion of glycolipid metabolism

Article

Author: Tang, Ning ; Snezhko, Eduard V ; Lu, Yin ; Sun, Yandi ; Zhang, Lihong ; Snezhko, Eduard V. ; Lin, Yindan ; Li, Hanhui ; Kovalev, Vassili A ; Huang, Yuqiao ; Kovalev, Vassili A. ; Wang, Ben ; Luo, Yan ; Zhang, Xueyun

Drug resistance is an inherent challenge during cancer chemotherapy. Cancer cells favor fatty acid metabolism through metabolic reprogramming to achieve therapeutic resistance. However, an effective approach to overcoming the switch from glycolysis-dependent to fatty acid beta-oxidation-dependent anabolic and energy metabolism remains elusive. Here, we developed a macromolecular drug (folate-polySia, FpSA) to induce the extracellular microcalcification of cervical cancer cells with cisplatin resistance. Microcalcification attenuated the uptake of fatty acids and the beta-oxidation of fatty acids by mitochondrial dysfunction but boosted the glycolysis pathway. Consequently, cotreatment with Pt and FpSA inhibited cisplatin-resistant tumor growth and improved tumor-bearing mice's survival rates, indicating that FpSA switched fatty acid metabolism to glycolysis to sensitize cisplatin-resistant cells further. Taken together, cancer cell calcification induced by FpSA provides a reprogramming metabolic strategy for the treatment of chemotherapy-resistant tumors.

854

News (Medical) associated with Cisplatin

31 Oct 2024

·www.globenewswire.com

Zymeworks Provides Corporate Update and Reports Third Quarter 2024 Financial Results

First patient dosed in Phase 1 clinical trial evaluating ZW171 in advanced mesothelin (MSLN)-expressing cancers Preclinical data presented on ZW220 and ZW251 at EORTC-NCI-AACR conferenceOur partner Jazz Pharmaceuticals presented new and updated clinical data at ESMO 2024 on zanidatamab highlighting its potential for the treatment of multiple HER2-positive (HER+) indicationsZymeworks to host in-person and virtual R&D day in New York City on December 12, 2024The Company has completed the initial $30 million of its Share Repurchase Program for 2,545,402 shares at an average price per share of $11.79 as of October 31, 2024Reported $374.9 million in cash resources as of September 30, 2024, which when combined with certain anticipated regulatory milestone payments provides a projected cash runway into 2H 2027Will host conference call with management today at 4:30 p.m. Eastern Time (ET) VANCOUVER, British Columbia, Oct. 31, 2024 (GLOBE NEWSWIRE) -- Zymeworks Inc. (Nasdaq: ZYME), a clinical-stage biotechnology company developing a diverse pipeline of novel, multifunctional biotherapeutics to improve the standard of care for difficult-to-treat diseases, today reported financial results for the three and nine months ended September 30, 2024 and provided a summary of recent business highlights. “2024 has been a pivotal year for us so far, marking several significant firsts across our pipeline. Our partner Jazz Pharmaceuticals has submitted a New Drug Application for zanidatamab, the late-stage HER2-targeting bispecific antibody to the FDA and we eagerly anticipate the potential for its first United States approval in second-line biliary tract cancer, with an assigned action date of November 29. This would be an important achievement not only for us and our partners Jazz and BeiGene, but for BTC patients with limited treatment options,” said Kenneth Galbraith, Chair and Chief Executive Officer of Zymeworks. “In parallel, we’ve dosed the first patient in our global Phase 1 study for our first bispecific T cell engager, ZW171.” Mr. Galbraith continued, “We believe that the novel design for our nominated candidates represents the next wave of innovation in oncology. As we continue to advance these early-stage assets into the clinic, we are also strategically expanding our focus on new modalities and therapeutic areas within our next generation of R&D candidates, broadly in solid tumors, hematologic cancers and autoimmune and inflammatory diseases. Later this year, we look forward to sharing more about these next-generation of antibody-drug conjugates and multi-specific antibodies which leverage our technology platforms to target multiple disease pathways. We believe this approach will be key to continue driving the long-term growth of our R&D pipeline and delivering transformative therapies to patients worldwide.” Recent Highlights and Current Developments The Company will host an in-person and virtual R&D day in New York, NY on December 12, 2024. A live webcast of the event will be available via the Investor section of our company website and will begin at 8:30 am Eastern Time. As part of the event, we will feature in-depth presentations including: Updates on our portfolio of solid tumor targeting antibody-drug conjugates (ADCs) and T-cell engager (TCE) molecules, featuring key opinion leaders from these therapeutic areas who will join the Company’s management team to discuss ongoing R&D and clinical activities;Candidate nomination from our Trispecific TCE platform as the last product candidate selected in our '5 by 5' R&D strategy; andStrategy and rationale for expansion into new therapeutic areas in hematological cancers and autoimmune and inflammatory diseases and preclinical development progress on potential investigational new drug (IND) applications for multiple new product candidates in 2026 and beyond. Progression of Wholly-Owned Research & Development Programs In October 2024, we announced that the first patient has been dosed in the first-in-human Phase 1 trial (NCT06523803) to evaluate the safety and tolerability of the investigational therapy ZW171 in the treatment of advanced or metastatic ovarian cancer, non-small cell lung cancer (NSCLC), and other MSLN-expressing cancers. The Phase 1 study is a two-part, open-label, multi-center study that is expected to enroll approximately 160 adult patients with advanced MSLN-expressing cancers. Part 1 of the study will evaluate the safety and tolerability of ZW171 and involve dose escalation in patients with advanced ovarian and NSCLC, with secondary endpoints assessing pharmacokinetics and confirmed objective response rate. Part 2 of the study will involve dose expansion in three cohorts (ovarian cancer, NSCLC, and a basket cohort enrolling patients with any MSLN-expression) and will evaluate the anti-tumor activity of ZW171, with primary endpoints focused on safety and tolerability and secondary endpoints assessing progression-free survival (PFS), duration of response (DoR) rates, and overall survival. The Company expects to conduct the Phase 1 study at investigator sites in North America, Europe, and the Asia-Pacific region.The Company is actively recruiting patients in the global Phase 1, open-label, multicenter study of ZW191 (NCT06555744). The study aims to enroll 145 participants with advanced solid tumors across North America, Europe, and the Asia-Pacific region. The study is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of ascending doses of ZW191.In October 2024, Zymeworks presented preclinical data at the European Organisation for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research (ENA) Conference on two ADC product candidates, ZW220 and ZW251, both of which are scheduled for IND applications in 2025. Presentations included: An oral presentation titled “ZW220, a NaPi2b-directed topoisomerase I inhibitor Antibody-Drug Conjugate, demonstrates compelling preclinical activity in NSCLC, ovarian and uterine cancer models, with a favorable toxicology profile in non-human primates”A poster presentation titled “ZW251, a novel glypican-3-targeting antibody-drug conjugate bearing a topoisomerase I inhibitor payload, demonstrates compelling preclinical activity in hepatocellular carcinoma models” “We’re thrilled to have presented promising preclinical data at several key scientific conferences this year, including the ENA conference in October, and these presentations continue to underscore the breadth, diversity and strength of our platform,” stated Paul Moore, Ph.D., Chief Scientific Officer at Zymeworks. “Specifically, preclinical data on our NaPi2b- and glypican-3-targeting antibody-drug conjugates have demonstrated both potent and selective anti-tumor activity in multiple cancer models, with favorable toxicology profiles and robust tumor growth inhibition, highlighting the transformative potential of our approach utilizing our proprietary payload and antibody. We anticipate submitting INDs and non-U.S. applications in the first half of 2025 for ZW220, and in the second half of 2025 for ZW251.” Zanidatamab Continues to Progress with Promising Developments In September 2024, our partner Jazz announced new and updated presentations at the European Society of Medical Oncology (ESMO) Annual Congress 2024 on zanidatamab highlighting its potential for the treatment of multiple HER2+ indications, including HER2+ metastatic gastroesophageal adenocarcinoma (mGEA) and advanced/metastatic colorectal cancer (mCRC). The presentations included: Efficacy and tolerability findings from an ongoing, open-label Phase 2 study (NCT03929666) evaluating zanidatamab in combination with chemotherapy as first-line treatment for patients with HER2-expressing metastatic GEA, which comprises gastric, esophageal and gastroesophageal junction adenocarcinomas. Data from 41 patients with HER2-positive metastatic GEA who were treated with zanidatamab in combination with physician’s choice of chemotherapy treatment demonstrated a median progression-free survival (mPFS) of 15.2 [95% CI: 9.5, 33.4] months. After a median duration of follow-up of 41.5 (range, 23.0-52.7) months, the median overall survival was not mature, a Kaplan-Meier-estimated 24-month overall survival was 65% [95% CI: 48.0, 78.0] and the 30-month overall survival was 59% [95% CI: 41.0, 73.0].A mini-oral presentation from another arm of the Phase 2, open-label trial (NCT03929666) that includes a cohort of patients with metastatic colorectal cancer treated with first-line zanidatamab plus chemotherapy ± bevacizumab (bev). In 11 response-evaluable patients, there were 10 confirmed partial responses and one patient with stable disease as a best response. The cORR was 91% (95% CI: 58.7, 99.8) and median DoR was not reached (2.9+,16.7+ months). All patients experienced treatment related adverse events (TRAEs) – Grade 3-4 TRAEs occurred in five (38%) patients, three (23%) of whom experienced diarrhea. No patients discontinued zanidatamab due to a TRAE and there were no treatment-related deaths. Zanidatamab plus chemotherapy ± bev demonstrated encouraging anti-tumor activity with a generally manageable safety profile as first-line treatment for patients with HER2-positive metastatic colorectal cancer.A poster presentation on the trial design for the ongoing, global, Phase 3, randomized, open-label trial (NCT06282575) investigating the efficacy and safety of zanidatamab with cisplatin and gemcitabine (CisGem) versus CisGem alone ± a programmed cell death protein-1/ligand 1 (PD-1/L1) inhibitor (pembrolizumab or durvalumab at physician’s discretion if locally approved) as first-line treatment for patients with advanced HER2-positive BTC. The primary endpoint is PFS in patients with immunohistochemistry (IHC) 3+ tumors. Secondary/exploratory endpoints include: overall survival (IHC 3+ subgroup; overall population), PFS (overall population), cORR, incidence and severity of adverse events and patient-reported outcomes. The study is currently recruiting patients. Business Updates As of September 30, 2024, Zymeworks has repurchased 1,818,530 shares of the Company’s common stock for a cost of $20.6 million, under the Repurchase Program announced in August 2024. As of October 31, 2024, the Company has completed the initial $30 million of the Repurchase Program for 2,545,402 shares at an average price per share of $11.79.On October 15, 2024, Hollings C. Renton submitted his resignation from Zymeworks’ board of directors, including as chair and member of the board of directors’ compensation committee, effective December 10, 2024 (the date of the Company’s 2024 Annual General Meeting of Stockholders). Mr. Renton’s resignation was not the result of any disagreement with the Company on any matter relating to the Company’s operations, policies or practices. Financial Results for the Nine Months Ended September 30, 2024 Revenue was $45.3 million for the nine months ended September 30, 2024 compared to $59.1 million for the same period in 2023. Revenue for the nine months ended September 30, 2024 included $32.8 million for development support and drug supply revenue from Jazz, $8.0 million of milestone revenue from BeiGene in relation to the acceptance by the CDE of the NMPA in China of the BLA for zanidatamab for 2L treatment of HER2-positive BTC, $2.5 million of milestone revenue from GSK in relation to the sequence pair nomination under the 2016 licensing agreement and $2.0 million from BeiGene and other partners for research support payments. Revenue for the same period in 2023 included $56.3 million for development support and drug supply revenue from Jazz and $2.8 million from BeiGene and our other partners for research support and other payments. The decrease in revenue from Jazz reflects the transfer of responsibility for certain clinical trials regarding zanidatamab to Jazz, with such future costs to be borne by Jazz instead of being incurred by us and reimbursed by Jazz. Research and development expense was $97.6 million for the nine months ended September 30, 2024 compared to $118.1 million for the same period in 2023. The decrease in research and development expense was primarily due to a decrease in expenses for zanidatamab, as a result of transfer of responsibility for this program to Jazz, and a decrease in expenses for ZW171 and ZW191. This decrease, compared to the same period in 2023, was partially offset by an increase in expenses for ZW220 and ZW251 and other preclinical and research activities. Stock-based compensation expense increased primarily due to a lower expense in 2023 as a result of the cancellation and modification of awards in respect of employees transferred to Jazz. General and administrative expense was $45.3 million for the nine months ended September 30, 2024 compared to $55.6 million for the same period in 2023. The decrease in general and administrative expense was primarily due to a decrease in external consulting expenses for information technology, legal fees, and other expenses for advisory services, insurance and depreciation and amortization expenses compared to the same period in 2023. This was partially offset by costs incurred due to the termination of our long-term facility lease in Seattle in 2024 and an increase in stock-based compensation expense over 2023, primarily due to reversal of compensation expense for options cancellations and modifications in 2023. During the nine months ended September 30, 2024, we recorded a non-cash impairment charge of $17.3 million as a result of our decision to discontinue the zanidatamab zovodotin clinical development program which utilized the technology represented by acquired in-process research and development assets. Other income, net was $16.1 million for the nine months ended September 30, 2024 compared to $14.6 million for the same period in 2023. The increase was primarily driven by an increase in the average interest yields of these investments during the period. Income tax expense decreased by $3.8 million for the nine months ended September 30, 2024 compared to the same period in 2023, primarily due to a reduction in U.S. taxes under the global intangible low-taxed income rules and Subpart F income rules for the nine months ended September 30, 2024. Net loss for the nine months ended September 30, 2024 was $99.2 million compared to $104.2 million loss for the same period in 2023. The decrease in net loss was primarily due to lower research and development and general and administrative expenses, as well as a decrease in income tax expense, which was partially offset by a decrease in revenue and an impairment charge recognized in 2024, related to zanidatamab zovodotin. As of September 30, 2024, we had $374.9 million of cash resources consisting of cash, cash equivalents and marketable securities, comprised of $122.4 million in cash and cash equivalents and $252.5 million in marketable securities. Based on current operating plans and assuming receipt of certain anticipated regulatory milestones, we expect our existing cash resources as of September 30, 2024, when combined with such anticipated milestone payments, will enable us to fund planned operations into the second half of 2027. About Zymeworks Inc. Zymeworks is a global clinical-stage biotechnology company committed to the discovery, development, and commercialization of novel, multifunctional biotherapeutics. Zymeworks’ mission is to make a meaningful difference in the lives of people impacted by difficult-to-treat cancers and other diseases. The Company’s complementary therapeutic platforms and fully integrated drug development engine provide the flexibility and compatibility to precisely engineer and develop highly differentiated antibody-based therapeutic candidates. Zymeworks engineered and developed zanidatamab, a HER2-targeted bispecific antibody using the Company’s proprietary Azymetric™ technology. Zymeworks has entered into separate agreements with BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each exclusive rights to develop and commercialize zanidatamab in different territories. Zanidatamab is currently being evaluated in multiple global clinical trials as a potential best-in-class treatment for patients with HER2-expressing cancers. A Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for zanidatamab as a treatment for previously-treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC) has been accepted and granted Priority Review. A BLA has also been accepted for review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China. If approved, zanidatamab would be the first HER2-targeted treatment specifically approved for BTC in the U.S. and China. Zymeworks is rapidly advancing a deep pipeline of product candidates based on its experience and capabilities in both antibody-drug conjugates and multispecific antibody therapeutics across multiple novel targets in indications that represent areas of significant unmet medical need. Phase 1 studies for ZW171 and ZW191 are now actively recruiting. In addition to Zymeworks’ wholly owned pipeline, its therapeutic platforms have been further leveraged through strategic partnerships with global biopharmaceutical companies. For information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on X. Cautionary Note Regarding Forward-Looking Statements This press release includes “forward-looking statements” or information within the meaning of the applicable securities legislation, including Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements in this press release include, but are not limited to, statements that relate to Zymeworks’ expectations regarding implementation of its strategic priorities; the anticipated benefits of the collaboration agreements with Jazz and BeiGene, including Zymeworks’ ability to receive any future milestone payments and royalties thereunder; the potential addressable market of zanidatamab; the timing of and results of interactions with regulators; Zymeworks’ clinical development of its product candidates and enrollment in its clinical trials; the timing and status of ongoing and future studies and the related data; anticipated preclinical and clinical data presentations; expectations regarding future regulatory filings and approvals and the timing thereof; the timing of and results of interactions with regulators; potential safety profile and therapeutic effects of zanidatamab and Zymeworks’ other product candidates; expected financial performance and future financial position; the commercial potential of technology platforms and product candidates; Zymeworks’ ability to satisfy potential regulatory and commercial milestones with existing and future partners; the timing and status of ongoing and future studies and the release of data; anticipated continued receipt of revenue from existing and future partners; Zymeworks’ early-stage pipeline; anticipated sufficiency of existing cash resources and certain anticipated regulatory milestone payments to fund Zymeworks’ planned operations into the second half of 2027; Zymeworks’ ability to execute new collaborations and partnerships and other information that is not historical information. When used herein, words such as “plan”, “believe”, “expect”, “may”, “continue”, “anticipate”, “potential”, “will”, “progress”, and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon Zymeworks’ current expectations and various assumptions. Zymeworks believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. Zymeworks may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various factors, including, without limitation: any of Zymeworks’ or its partners’ product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; Zymeworks may not achieve milestones or receive additional payments under its collaborations; regulatory agencies may impose additional requirements or delay the initiation of clinical trials; the impact of new or changing laws and regulations; market conditions; the impact of pandemics and other health crises on Zymeworks’ business, research and clinical development plans and timelines and results of operations, including impact on its clinical trial sites, collaborators, and contractors who act for or on Zymeworks’ behalf; clinical trials may not demonstrate safety and efficacy of any of Zymeworks’ or its collaborators’ product candidates; Zymeworks’ assumptions and estimates regarding its financial condition, future financial performance and estimated cash runway may be incorrect; inability to maintain or enter into new partnerships or strategic collaborations; and the factors described under “Risk Factors” in Zymeworks’ quarterly and annual reports filed with the Securities and Exchange Commission (copies of which may be obtained at www.sec.gov and www.sedar.com). Although Zymeworks believes that such forward-looking statements are reasonable, there can be no assurance they will prove to be correct. Investors should not place undue reliance on forward-looking statements. The above assumptions, risks and uncertainties are not exhaustive. Forward-looking statements are made as of the date hereof and, except as may be required by law, Zymeworks undertakes no obligation to update, republish, or revise any forward-looking statements to reflect new information, future events or circumstances, or to reflect the occurrences of unanticipated events. ZYMEWORKS INC. Condensed Interim Consolidated Statements of Loss and Comprehensive Loss (Expressed in thousands of U.S. dollars except share and per share data) (unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenue Research and development collaborations$ 16,000 $ 16,506 $ 45,273 $ 59,086 Operating expenses: Research and development 36,353 32,775 97,558 118,095 General and administrative 13,852 16,968 45,321 55,623 Impairment on acquired in-process research and development assets — — 17,287 — Total operating expenses 50,205 49,743 160,166 173,718 Loss from operations (34,205) (33,237) (114,893) (114,632)Other income, net 4,581 5,660 16,073 14,594 Loss before income taxes (29,624) (27,577) (98,820) (100,038)Income tax expense (226) (1,110) (369) (4,154)Net loss$ (29,850) $ (28,687) $ (99,189) $ (104,192)Other comprehensive income (loss): Unrealized income (loss) on available for sale securities, net of tax of nil 1,905 (485) 604 (1,639)Total other comprehensive income (loss) 1,905 (485) 604 (1,639)Comprehensive loss$ (27,945) $ (29,172) $ (98,585) $ (105,831) Net loss per common share: Basic$ (0.39) $ (0.41) $ (1.30) $ (1.53)Diluted$ (0.39) $ (0.41) $ (1.30) $ (1.53)Weighted-average common stock outstanding: Basic 76,128,531 70,575,773 76,244,893 68,212,756 Diluted 76,157,101 70,575,773 76,266,177 68,214,482 ZYMEWORKS INC.Condensed Consolidated Balance Sheet(Expressed in thousands of U.S. dollars) (unaudited) September 30,2024 December 31,2023 Assets Current assets: Cash, cash equivalents and short-term marketable securities$ 297,200 $ 374,327 Accounts receivable 23,704 19,477 Other current assets 22,865 19,122 Long-term marketable securities 77,667 81,930 Other long-term assets 65,716 86,024 Total assets$ 487,152 $ 580,880 Liabilities Current liabilities: Accounts payable and accrued expenses$ 51,707 $ 45,992 Other current liabilities 32,202 9,771 Long-term liabilities 36,265 60,311 Total liabilities 120,174 116,074 Stockholders’ equity 366,978 464,806 Total liabilities and stockholders’ equity$ 487,152 $ 580,880 Contacts: Investor Inquiries:Shrinal InamdarDirector, Investor Relations(604) 678-1388 ir@zymeworks.com Media Inquiries:   Diana PapoveSenior Director, Corporate Communications(604) 678-1388   media@zymeworks.com

Phase 1Clinical ResultPhase 2Phase 3

31 Oct 2024

·www.prnewswire.com

Intensity Therapeutics, Inc. and The Swiss Group for Clinical Cancer Research SAKK Announce the First Patient Dosed in the Randomized, Presurgical Triple Negative Breast Cancer Phase 2 Clinical Trial (INVINCIBLE-4 / SAKK 66/22)

Testing the efficacy and safety of Intensity's lead drug candidate, INT230-6, when combined with Standard-of-Care versus Standard-of-Care alone The endpoint is the change in pathological complete response rates SHELTON, Conn. and BERN, Switzerland, Oct. 31, 2024 /PRNewswire/ -- Intensity Therapeutics, Inc. ("Intensity" or "the Company") (Nasdaq: INTS), a late-stage clinical biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumorally injected cancer therapies intended to kill tumors directly and increase immune system recognition of cancers, and The Swiss Group for Clinical Cancer Research SAKK ("SAKK"), a decentralized academic research institute that has been conducting clinical trials of cancer treatments in all major Swiss hospitals since 1965, are collaborating in the INVINCIBLE-4 Study, a Phase 2 trial to treat patients with localized triple-negative breast cancer ("TNBC"), and announce that the first patient has been dosed in the study. The trial (NCT06358573) analyzes INT230-6 given before administration of the standard-of-care neoadjuvant immuno-chemotherapy ("SOC") and the SOC alone by using a 2-cohort design. The study evaluates the pathological complete response ("pCR") rates of the two cohorts relative to a null hypothesis, which is a pCR rate of ≤ 0.6. The success of each cohort in rejecting the null hypotheses will be evaluated. The Phase 2 study is expected to enroll approximately 54 patients in Switzerland and France. The INVINCIBLE-4 Study is a randomized open-label, multicenter study to determine the clinical activity, safety, and tolerability of INT230-6 in patients with early-stage, operable TNBC who undergo SOC treatment and SOC alone. The primary endpoint is pCR in the primary tumor and affected lymph nodes. Patients will be randomized one to one to receive a regimen of either two doses of INT230-6 followed by SOC, which consists of pembrolizumab, anthracyclines, carboplatin, cyclophosphamide and paclitaxel, or to the SOC alone. The INVINCIBLE-4 Study initiation follows data reported from the Company's INVINCIBLE-2 Study, where INT230-6 given alone showed tumor-killing properties at levels greater than 95% on a single intratumoral dose with systemic immune activation. "Many TNBC patients undergoing SOC treatment alone fail to achieve a pathological complete response at the time of surgery, especially in larger tumor sizes. INT230-6 has the potential to fill this unmet need for aggressive subtypes, such as TNBC, through its anti-cancer mechanisms of action that cause tumor cell necrosis and ignite an anti-cancer immune-based response," said Andreas Mueller, M.D. Past-President of the Breast Cancer Group at the National Swiss Association for Clinical Cancer Research in Bern Switzerland and Head of Department of Medicine at the Kantonsspital in Winterthur and a supporting coordinating investigator for the study. "The ability for INT230-6 to induce necrosis and activate immune effects before a patient's surgery without increases in toxicity would be a major advance for the treatment of breast cancer and potentially many other cancers." "The majority of breast cancers are immune quiescent, resulting in minimal response to immunotherapies, and larger tumors are less responsive to therapy," said Ursina Zuerer-Haerdi, MD and Lead Physician for the Department of Medical Oncology and Hematology at the Cantonal Hospital in Winterthur, Switzerland and a supporting coordinating investigator on the study. "We have worked with Intensity to design a study for this novel intratumoral agent with the potential to increase the pathological complete response rates of the current best standard of care that would be clinically meaningful, and this trial is of high interest to SAKK's physician network." "INT230-6 is an innovative investigational product that combines cisplatin and vinblastine with a penetration enhancer molecule (SHAO)," said Markus Joerger, Prof. MD-PhD and Coordinating Investigator on the study and principal investigator for the Department of Medical Oncology and Hematology at the Cantonal Hospital St. Gallen. INT230-6 results in local immunogenic cell death when injected into the breast tumor, without systemic chemotoxicity but a high potency to induce systemic immunostimulatory effects. INT230-6 tackles the innate immune pathway that is not addressed by immune checkpoint inhibitors, and it is suggested to complement the systemic neoadjuvant backbone in study patients with early-stage TNBC which consists of chemotherapy and the checkpoint inhibitor pembrolizumab. We believe that the SAKK 66/22 study will provide crucial data to inform a large randomized clinical trial in patients with early-stage TNBC, a disease that is still burdened by substantial rates of fatal relapses following potentially curative treatment." "We are excited to have initiated our Phase 2 study in presurgical triple-negative breast cancer. This study marks the first European patient treated with our drug - a new milestone. Triple-negative is a deadly and aggressive form of breast cancer, and patients having local disease currently undergo a harsh four to six-month regimen whereby a small percentage can die from the SOC before their surgery. Those patients who achieve a pCR have a lower risk of disease recurrence," said Intensity Therapeutics' Founder, Chairman, and CEO, Lewis H. Bender. "We hope that by killing a substantial amount of the tumor upfront and increasing the immune response using INT230-6, we can increase the percentage of patients who achieve pCR and ultimately an improved event-free survival." About INT230-6 INT230-6, Intensity's lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity's proprietary DfuseRx℠ technology platform. The drug comprises two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor, resulting in a favorable safety profile. In addition to local disease control and direct tumor killing, INT230-6 has been shown to release a bolus of neoantigens specific to the malignancy, leading to immune system engagement and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression, which often occurs with systemic chemotherapy. About Triple Negative Breast Cancer in the Presurgical Setting Approximately 11-17% of breast cancers test negative for estrogen receptors (ER), progesterone receptors (PR), and excess human epidermal growth factor receptor 2 (HER2) protein, qualifying them as triple negative. TNBC is considered to be more aggressive and has a poorer prognosis than other types of breast cancer, mainly because there are fewer available targeted medicines. Most patients with local TNBC typically receive immune/chemotherapy before surgery. Since the publication of Keynote-522, standard neoadjuvant treatment for TNBC includes systemic chemotherapy (anthracyclines, cyclophosphamide, paclitaxel, carboplatin) and the anti-PD-1 monoclonal antibody pembrolizumab. pCR rates are only 63%, with rates generally lower in the larger-sized T2 to T4 tumors. The toxicity of the Keynote-522 regimen is high, with 80% of patients experiencing grade 3 or higher treatment-related AEs, including treatment-related adverse events that lead to death in 0.5% of patients. About SAKK The Swiss Group for Clinical Cancer Research (SAKK) is a decentralized academic research institute that has been conducting clinical trials of cancer treatments in all major Swiss hospitals since 1965. It federates a large network of research groups with a Competence Center in Bern in charge of coordinating the clinical operations. It also works with selected cooperative groups abroad, particularly on rare forms of cancer. SAKK's aim is to advance existing cancer treatments, investigate the efficacy and tolerability of new treatments (radiotherapy, medicines and surgery), and set new standards in treatment. 22 Swiss hospitals are full members of SAKK. Research activity is funded by federal subsidies provided by the State Secretariat for Education, Research and Innovation (SERI) and financial support from other partner organizations such as the Swiss Cancer League and the Swiss Cancer Research Foundation. Further information can be found at . About Intensity Therapeutics Intensity Therapeutics is a late-stage clinical biotechnology company that applies novel engineered chemistry by enabling its aqueous cytotoxic-containing drug product, INT230-6, to mix and saturate the tumor's dense, high-fat pressurized environment. As a result of the saturation, Intensity's clinical trials have demonstrated the ability of INT230-6 to kill tumors and elicit an adaptive immune response within days of injection, representing a novel approach to cancer cell death that holds the potential to shift the treatment paradigm and turn many deadly cancers into chronic diseases even for cancers that do not respond to immunotherapy. Intensity complete two large clinical studies using INT230-6 that enrolled over 200 patients: a Phase 1/2 dose escalation trial (NCT03058289) and a Phase 2 randomized control clinical trial in breast cancer (the INVINCIBLE-2 study) (NCT04781725). Intensity Therapeutics initiated a Phase 3 trial in soft tissue sarcoma (the INVINCIBLE-3 study) (NCT06263231), testing INT230-6 as second or third-line monotherapy compared to the standard of care with overall survival as an endpoint. The Company is also conducting a Phase 2 study in collaboration with SAKK as part of a Phase 2/3 program evaluating INT230-6 followed by SOC and SOC alone for patients with presurgical triple negative breast cancer. Information on the Phase 2 portion of the program (INVINCIBLE-4 Study) is listed under (NCT06358573). For more information about the Company, including publications, papers and posters about its novel approach to cancer therapeutics, visit . Forward-Looking Statements Certain statements in this press release may constitute "forward-looking statements" within the meaning of the United States Private Securities Litigation Reform Act of 1995, as amended to date. These statements include but are not limited to, statements relating tothe development of the Company's clinical programs. When or if used in this communication, the words "may," "could," "should," "anticipate," "believe," "estimate," "expect," "intend," "plan," "predict" and similar expressions and their variants, as they relate to the Company or its management, may identify forward-looking statements. The forward-looking statements contained in this press release are based on management's current expectations and projections about future events. Nevertheless, actual results or events could differ materially from the plans, intentions, and expectations disclosed in, or implied by, the forward-looking statements. These risks and uncertainties, many of which are beyond our control, include: the initiation, timing, progress and results of future preclinical studies and clinical trials and research and development programs; the need to raise additional funding before the Company can expect to generate any revenues from product sales; plans to develop and commercialize product candidates; the timing or likelihood of regulatory filings and approvals; the ability of the Company's research to generate and advance additional product candidates; the implementation of the Company's business model, strategic plans for the Company's business, product candidates and technology; commercialization, marketing and manufacturing capabilities and strategy; the rate and degree of market acceptance and clinical utility of the Company's system; the Company's competitive position; the Company's intellectual property position; developments and projections relating to the Company's competitors and its industry; the Company's ability to maintain and establish collaborations or obtain additional funding; expectations related to the use of cash and cash equivalents and investments; estimates regarding expenses, future revenue, capital requirements and needs for additional financing; and other risks described in the section entitled "Risk Factors" in the Company's SEC filings, which can be obtained on the SEC website at . Readers are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date on which they are made and reflect management's current estimates, projections, expectations and beliefs. The Company does not plan to update any such forward-looking statements and expressly disclaims any duty to update the information contained in this press release except as required by law. Investor Relations Contact: Justin Kulik [email protected] CORE IR (516) 222-2560 Media Contact: Jules Abraham CORE IR [email protected] SOURCE Intensity Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2ImmunotherapyClinical ResultPhase 3

31 Oct 2024

·pipelinereview.com

Three Phase 3 Trials of Datopotamab Deruxtecan-Based Combinations Initiated in Patients with Advanced Nonsquamous Non-Small Cell Lung Cancer

TOKYO, Japan & BASKING RIDGE, NJ, USA I October 30, 2024 I The first patients have been dosed in three global, randomized phase 3 trials evaluating the efficacy and safety of datopotamab deruxtecan (Dato-DXd)-based combinations in patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). TROPION-Lung10 is evaluating datopotamab deruxtecan plus rilvegostomig, AstraZeneca’s PD-1/TIGIT bispecific antibody, or rilvegostomig alone versus pembrolizumab in patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with high PD-L1 expression (tumor cells [TC] ≥ 50%) and without actionable genomic alterations. TROPION-Lung14 is evaluating datopotamab deruxtecan plus osimertinib, AstraZeneca’s EGFR tyrosine kinase inhibitor (TKI), versus osimertinib alone in patients with previously untreated locally advanced or metastatic EGFR mutated nonsquamous NSCLC. TROPION-Lung15 is evaluating datopotamab deruxtecan with or without osimertinib versus platinum-based doublet chemotherapy in patients with locally advanced or metastatic nonsquamous EGFR mutated NSCLC whose disease progressed on prior treatment with osimertinib. “These three trials in either high PD-L1 expressing or EGFR mutated nonsquamous non-small cell lung cancer are critical to helping us understand the potential role of datopotamab deruxtecan in treating patients across different lines and types of lung cancer,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “Our growing TROPION clinical program, which now consists of seven phase 3 trials demonstrates our commitment to understanding the full potential of datopotamab deruxtecan in lung cancer.” “Clinical research suggests that combining an antibody drug conjugate with a targeted treatment or a bispecific immunotherapy may drive stronger and more durable tumor responses in patients with a variety of cancers including lung cancer,” said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. “The initiation of these additional three phase 3 trials of datopotamab deruxtecan in combination with our agents, osimertinib and rilvegostomig illustrates our commitment to exploring potential synergies within our oncology pipeline as well as the full potential and combinability of this TROP2 directed antibody drug conjugate across multiple segments and settings of non-small cell lung cancer.” About TROPION-Lung10 TROPION-Lung10 is a global, multicenter, open-label, three-arm phase 3 trial where patients will be randomized in a 2:1:2 ratio to evaluate the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) in combination with rilvegostomig (750 mg) or rilvegostomig (750 mg) monotherapy versus pembrolizumab (200 mg) monotherapy in adult patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations. The dual primary endpoints of TROPION-Lung10 are progression-free survival (PFS) as assessed by blinded independent central review (BICR) and overall survival (OS) in patients with TROP2 positive tumors receiving datopotamab deruxtecan in combination with rilvegostomig versus the pembrolizumab arm. A pre-specified retrospective analysis from tumor biopsies collected pretreatment will be conducted following validation of a potential TROP2 biomarker determined by quantitative continuous scoring, a computational pathology approach. Key secondary endpoints for all arms of the trial include PFS as assessed by BICR and investigator and OS in the intention-to-treat (ITT) population, objective response rate (ORR) as assessed by BICR and duration of response (DoR) as assessed by BICR and investigator in both TROP2 biomarker positive and the ITT populations. The safety and tolerability of datopotamab deruxtecan in combination with rilvegostomig and rilvegostomig monotherapy as compared with pembrolizumab also will be assessed. TROPION-Lung10 will enroll approximately 675 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . The TIGIT component of rilvegostomig is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen Ltd. (Nasdaq/TASE: CGEN). About TROPION-Lung14 TROPION-Lung14 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) in combination with osimertinib (80 mg) versus osimertinib (80 mg) monotherapy in adult patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with an EGFR mutation (Exon 19 deletion and/or L858R). The randomized period of the trial is preceded by a single-arm safety run-in period which will enroll approximately 20 patients to evaluate the combination therapy. The primary endpoint of TROPION-Lung14 is PFS as assessed by BICR. Key secondary endpoints include central nervous system (CNS) PFS as assessed by CNS BICR, PFS as assessed by investigator, ORR as assessed by BICR and investigator, OS and safety. TROPION-Lung14 will enroll approximately 580 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . About TROPION-Lung15 TROPION-Lung15 is a global, multicenter, open-label, three-arm phase 3 trial where patients will be randomized in a 1:1:1 ratio to evaluate the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) as monotherapy or in combination with osimertinib (80 mg) versus platinum-based doublet chemotherapy (pemetrexed in combination with carboplatin or cisplatin followed by pemetrexed maintenance) in adult patients with locally advanced or metastatic nonsquamous NSCLC with at least one EGFR mutation (G719X, Ex19del, S768I, L858R, and/or L861Q) and with disease progression following prior treatment with osimertinib. The dual primary PFS endpoints of TROPION-Lung15 are PFS as assessed by BICR for datopotamab deruxtecan monotherapy versus chemotherapy and datopotamab deruxtecan in combination with osimertinib versus chemotherapy. Key secondary endpoints include investigator-assessed CNS PFS as assessed by CNS BICR, ORR and DoR as assessed by BICR, OS and safety. TROPION-Lung15 will enroll approximately 630 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . About Advanced Non-Small Cell Lung Cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. 1 NSCLC is the most common type of lung cancer, accounting for about 85% of cases. 2 Approximately 75% and 25% of NSCLC tumors are of nonsquamous or squamous histology, respectively, with EGFR mutations occurring in 14% to 38% of all NSCLC tumors worldwide. 3,4 A majority of EGFR mutations occur in tumors with nonsquamous histology. 5 For patients with tumors that do not express a known actionable genomic alteration (e.g., EGFR, ALK, ROS1, NTRK, BRAF, RET or MET), the current first-line standard of care in the metastatic setting is an immune checkpoint inhibitor and/or platinum-based chemotherapy based on PD-L1 expression. 6,7,8 For certain patients with tumors that have EGFR mutations, the established first-line treatment in the metastatic setting is an EGFR TKI. 9 While these treatment strategies have improved outcomes in the first-line metastatic setting, most patients eventually experience disease progression. 10,11,12 TROP2 is a protein broadly expressed in the majority of NSCLC tumors. 13 There is currently no TROP2 directed ADC approved for the treatment of lung cancer. 8,9 About Datopotamab Deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com . References 1 World Health Organization. Global Cancer Observatory: Lung . Accessed October 2024. 2 Economopoulou P, et al. Ann Transl Med . 2018; 6(8):138 3 National Cancer Institute. SEER Cancer Statistics Factsheets: Lung and Bronchus Cancer, CSR 1975-2017 . Accessed October 2024. 4 Pretelli G, et al. Int J Mol Sci . 2023; 24, 8878. 5 Prabhakar C. Translational Lung Cancer Research . 2015; 4(2), 110-118. 6 Mok TSK, et al. Lancet . 2019 May 4;393(10183):1819-1830. 7 Brahmer J.R. et al. KEYNOTE-024 5-year OS update . ESMO 2021 Virtual Congress. 2021 Sept 16 – 20; Abstract LBA51. 8 Rodríguez-Abreau D, et al. Ann Onc . 2021 Jul;32(7):881-895. 9 American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer . Accessed October 2024. 10 Chen R, et al. J Hematol Oncol . 2020:13(1):58. 11 Majeed U, et al. J Hematol Oncol . 2021;14(1):108. 12 Pircher A, et al. Anticancer Research . 2020;70(5):287-294. 13 Mito R, et al. Pathol Int . 2020;70(5):287-294. SOURCE: Daiichi Sankyo

Phase 3ImmunotherapyADCLicense out/in

100 Deals associated with Cisplatin

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KEGG	Wiki	ATC	Drug Bank
D00275	Cisplatin	L01XA01	DB00515

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Indication	Country/Location	Organization	Date
Biliary Tract Neoplasms	JP	Nippon Kayaku Co., Ltd.	22 Feb 2012
Malignant Pleural Mesothelioma	JP	Nippon Kayaku Co., Ltd.	04 Jan 2007
Childhood Malignant Solid Neoplasm	JP	Nippon Kayaku Co., Ltd.	15 Sep 2005
Lymphoma	JP	Nippon Kayaku Co., Ltd.	15 Sep 2005
Bone Cancer	JP	Nippon Kayaku Co., Ltd.	14 Feb 2005
Endometrial Carcinoma	JP	Nippon Kayaku Co., Ltd.	14 Feb 2005
Germinoma	JP	Nippon Kayaku Co., Ltd.	31 May 2004
Hepatocellular Carcinoma	JP	Nippon Kayaku Co., Ltd.	29 Jan 2004
Osteosarcoma	JP	Nippon Kayaku Co., Ltd.	21 Dec 1999
Small Cell Lung Cancer	JP	Nippon Kayaku Co., Ltd.	21 Dec 1999
Stomach Cancer	JP	Nippon Kayaku Co., Ltd.	03 Jun 1990
Esophageal Carcinoma	JP	Nippon Kayaku Co., Ltd.	30 May 1988
Neuroblastoma	JP	Nippon Kayaku Co., Ltd.	30 May 1988
Uterine Cervical Cancer	JP	Nippon Kayaku Co., Ltd.	30 May 1988
Non-Small Cell Lung Cancer	JP	Nippon Kayaku Co., Ltd.	28 Aug 1986
Kidney Neoplasms	JP	Nippon Kayaku Co., Ltd.	21 Sep 1983
Prostatic Cancer	JP	Nippon Kayaku Co., Ltd.	21 Sep 1983
Transitional Cell Carcinoma	JP	Nippon Kayaku Co., Ltd.	21 Sep 1983
Ureteral Neoplasms	JP	Nippon Kayaku Co., Ltd.	21 Sep 1983
Bladder Cancer	US	HQ Specialty Pharma Corp.	19 Dec 1978

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Indication	Highest Phase	Country/Location	Organization	Date
Fallopian Tube Carcinoma	Phase 3	US	GSK Plc	08 Mar 2024
Primary peritoneal carcinoma	Phase 3	US	GSK Plc	08 Mar 2024
Malignant Pleural Effusion	Phase 3	CN	Jiangsu Simcere Pharmaceutical Co., Ltd.	31 May 2021
Metastatic gastric adenocarcinoma	Phase 3	US	Eli Lilly & Co.	20 Jan 2015
Metastatic gastric adenocarcinoma	Phase 3	JP	Eli Lilly & Co.	20 Jan 2015
Metastatic gastric adenocarcinoma	Phase 3	AR	Eli Lilly & Co.	20 Jan 2015
Metastatic gastric adenocarcinoma	Phase 3	BE	Eli Lilly & Co.	20 Jan 2015
Metastatic gastric adenocarcinoma	Phase 3	CA	Eli Lilly & Co.	20 Jan 2015
Metastatic gastric adenocarcinoma	Phase 3	CZ	Eli Lilly & Co.	20 Jan 2015
Metastatic gastric adenocarcinoma	Phase 3	DK	Eli Lilly & Co.	20 Jan 2015

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02641847 (BCTOP-T-A01, Literature) Manual	Phase 3	Triple Negative Breast Cancer	498	docetaxel+doxorubicin or epirubicin+cyclophosphamide+gemcitabine+cisplatin (High risk group A)	cmswvzxobc(ihpixrssws) = qagrzlbntq erfasrvjbg (imtzzxipdb ) View more	Positive	23 Oct 2024
				docetaxel+doxorubicin or epirubicin+cyclophosphamide (High risk group B)	cmswvzxobc(ihpixrssws) = wscwdtcnsp erfasrvjbg (imtzzxipdb ) View more
NCT03768414 (SWOG 1815, CTgov)	Phase 3	Unresectable Intrahepatic Cholangiocarcinoma \| Advanced biliary tract cancer \| Gallbladder Neoplasms ... View more	452	Nab-paclitaxel+Gem+Cisplatin (Gem+Cisplatin+Nab-paclitaxel)	pkszhjbpmk(xytyeumbld) = nnqslwimog kymjxdqigi (ybynvvyues, trpqmogtgv - layzuhuagj) View more	-	22 Oct 2024
				Gemcitabine+Cisplatin (Gemcitabine + Cisplatin)	pkszhjbpmk(xytyeumbld) = pclujvfewk kymjxdqigi (ybynvvyues, tuoboidofj - ubgurobiqr) View more
NCT01088906 (Phalcis, CTgov)	Phase 2	Advanced Lung Non-Small Cell Squamous Carcinoma \| Non-squamous non-small cell lung cancer	57	Cisplatin+Pemetrexed (EXPERIMENTAL ARM)	bgiehdwqtx(wmurvkeslk) = grwtdicqba ofbfousqze (lllktutjnr, vgpaswortg - amyifllepj) View more	-	15 Oct 2024
				Cisplatin+Pemetrexed (Experimental Arm: Pemetrexed Plus Cisplatin)	bdjhwttyae(fvlruxxpuv) = aeuqrkfuxo tyquiwrpha (zflancoppp, dhcxqjhlqj - numfiqdjam) View more
NCT01074970 (BRE09-146, CTgov)	Phase 2	Triple Negative Breast Cancer	135	Cisplatin (Arm A: Cisplatin Monotherapy)	ujjjzdgvdm(ezytfvotfb) = yoefepxqai eseakatduj (onbaknaxze, pdskoonfcc - ucgpgclwtm) View more	-	19 Sep 2024
				Rucaparib+Cisplatin (Arm B: Combination Therapy)	ujjjzdgvdm(ezytfvotfb) = czhlrpgrit eseakatduj (onbaknaxze, jmgohadliq - bloevmdpxk) View more
NCT02202772 (ESMO2024) Manual	Phase 2	Non-Muscle Invasive Bladder Urothelial Carcinoma	33	cabazitaxel+gemcitabine+cisplatin	xdutdzigdi(cvqnmyytbv) = wjoizebbrr jcuhhfdlna (icfkjcxigt ) View more	Positive	15 Sep 2024
ESMO2024 Manual	Phase 2	Nonseminomatous Germ Cell Tumor	34	Paclitaxel+ifosfamide+cisplatin	fzbxgumbea(nvahmlesis) = nwiroqbthr smjdnzrgup (sfswwsxwkm ) View more	Negative	15 Sep 2024
JPRN-jRCTs051200138 (WJOG14120L NESSIE, ESMO2024) Manual	Phase 2	Advanced Lung Squamous Cell Carcinoma	46	Cisplatin and gemcitabine plus necitumumab (CGN)	ubqsfgcegx(pdruxgulqf) = hkdhwppdra jcgeqrguug (gimgmypjto, 17.7 - 36.2) View more	Positive	14 Sep 2024
ESMO2024 Manual	Phase 2	Non-Small Cell Lung Cancer	120	Cisplatin 75mg/m2 (group I)	quwirvkvon(ibpygpdhrm) = more frequent in group I mdpywebtfl (peidsglmku ) View more	Positive	14 Sep 2024
				Cisplatin 50mg fixed dose (group II)
NCT03047265 (ESMO2024) Manual	Phase 2	Nasopharyngeal Carcinoma	184	Paclitaxel plus Cisplatin	bszdfvbyga(kgymzoyyuc) = mdsxiacmdu zdysbyneyz (ienjqnjjll, 58.6 - 77.8)	Negative	14 Sep 2024
				Cisplatin	bszdfvbyga(kgymzoyyuc) = hexkpnfklo zdysbyneyz (ienjqnjjll, 63.8 - 81.8)
JPRN-jRCTs031180135 (JCOG1008, ESMO2024) Manual	Phase 2/3	Squamous Cell Carcinoma of Head and Neck	261	3-weekly Cisplatin+RT	nuftpxunuh(hvoeigqfie) = bklabclvyf ixuyjkcbeg (bnpsssoung ) View more	Positive	14 Sep 2024
				Weekly Cisplatin+RT	nuftpxunuh(hvoeigqfie) = upvawfnhxl ixuyjkcbeg (bnpsssoung ) View more

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Bio Sequences Search & Analysis

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Chemical Structures Search & Analysis