HER2 antagonists(Receptor tyrosine-protein kinase erbB-2 antagonists), TOP1 inhibitors(DNA topoisomerase I inhibitors), ADCC(Antibody-dependent cell-mediated cytotoxicity (ADCC) effects)

Therapeutic Areas

NeoplasmsDigestive System DisordersRespiratory Diseases+ [5]

Active Indication

Metastatic human epidermal growth factor 2 positive carcinoma of breastStomach CancerHER2 Positive Solid Tumors+ [66]

Inactive Indication

HER2 Positive Transitional Cell CarcinomaHER2-expressing Gastroesophageal Junction AdenocarcinomaMeningeal Carcinomatosis+ [1]

Originator Organization

Daiichi Sankyo Co., Ltd.

Active Organization

AstraZeneca PLC

AstraZeneca Canada, Inc.

Daiichi Sankyo, Inc.

+ [10]

Inactive Organization-

License Organization

Merck & Co., Inc.

AstraZeneca PLC

Daiichi Sankyo Co., Ltd.

+ [2]

Drug Highest PhaseApproved

First Approval Date

United States (20 Dec 2019),

HER2 Positive Breast Cancer

RegulationBreakthrough Therapy (United States), Fast Track (United States), Accelerated Approval (United States), Orphan Drug (United States), Conditional marketing approval (China), Orphan Drug (Japan), Orphan Drug (Australia), Priority Review (Australia), Breakthrough Therapy (China), Priority Review (United States), Priority Review (China), SAKIGAKE (Japan)

Structure/Sequence

Boost your research with our ADC technology data.

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Sequence Code 18481L

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Sequence Code 44772H

Source: *****

199

Clinical Trials associated with Fam-trastuzumab deruxtecan-NXKI

NCT07578116

/ Not yet recruitingPhase 3IIT

Randomized Phase III Trial of Multimodality Therapy Versus Standard of Care Systemic Therapy in HER2 Positive (HER2+) De Novo (AJCC Stage IV) Oligometastatic Breast Cancer With Response to Initial Chemotherapy

This phase III trial evaluates the effect of adding locoregional therapy (surgery and radiation) and metastasis-directed stereotactic body radiation therapy (SBRT) to standard systemic therapy following standard HER2-targeted systemic therapy, compared to standard systemic therapy alone, in treating patients with HER2-positive stage IV breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or to a limited number of sites (oligometastatic). The usual approach for patients with (oligo)metastatic HER2-positive breast cancer is systemic drug treatment, which means medicines that travel through the whole body to treat both the breast and any areas where the cancer has spread. There are a number of approved HER2-targeted systemic therapy regimens available to patients. These typically include immunotherapy and/or chemotherapy. Immunotherapy drugs may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs 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. Unlike systemic therapy, locoregional therapies like surgery and radiation are focused treatments at the site of disease, delivered with the intent of sparing healthy tissues. Breast surgeries such as breast conserving therapy or total mastectomy are procedures in which the cancerous breast tissue (and healthy breast tissue in the case of total mastectomy) are surgically removed from the body. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Adding locoregional therapy, as well as metastasis-directed SBRT, to standard systemic therapy may help patients with (oligo)metastatic, HER2-positive stage IV breast cancer live longer overall or before their cancer progresses, and may help more patients achieve no evidence of disease, when compared to standard systemic therapy alone.

Start Date09 Mar 2027

Sponsor / Collaborator

SWOG

[+1]

NCT07126561

/ Not yet recruitingPhase 2IIT

Phase II Open Label Trial of Trastuzumab Deruxtecan (Enhertu, DS-8210) in HER2 Positive Newly Diagnosed Metastatic Esophageal, Gastric, GEJ Cancer Patients With an ECOG Performance Status of 2

Purpose: This clinical trial is designed to evaluate the safety and effectiveness of Trastuzumab Deruxtecan for patients with HER2 Positive Newly Diagnosed Metastatic Esophageal, Gastric, GEJ Cancer. The goal is to determine how well this treatment works and to identify any potential side effects.
Who Can Participate: We are looking for Participants with histologically confirmed HER2 positive locally advanced unresectable and/or metastatic esophageal, gastric or GEJ adenocarcinoma with an ECOG PS of 2 and measurable disease according to RECIST 1.1 within 42 days prior to registration. Participants will be carefully screened to ensure they meet the study requirements.
What to Expect: Participants will undergo 6.4mg/kg, IV infusion of Trastuzumab deruxtucan over the course of the study. They will receive detailed information about the study and will have the opportunity to ask questions before deciding to participate. Informed consent will be obtained to ensure that participants understand the study's purpose, procedures, risks, and benefits.
Safety Monitoring: The health and safety of participants are our top priority. An Independent Data and Safety Monitoring Committee (DSMC) will regularly review the study data to ensure participant safety and to monitor for any adverse events. Any serious side effects will be reported and addressed promptly.
Benefits and Risks: While the study aims to provide potential benefits, such as improved treatment options for HER2 Positive Newly Diagnosed Metastatic Esophageal, Gastric, GEJ Cancer there may also be risks involved. Participants will be informed of all possible risks before enrolling in the study.
Confidentiality: All personal information will be kept confidential, and data will be used only for research purposes.
Contact Information: For more information about this study, please contact PhaseIICRA@medicine.bsd.uchicago.edu

Start Date01 Nov 2026

Sponsor / Collaborator

The University of Chicago

NCT07137416

/ RecruitingPhase 1IIT

Phase 1b Study of Pidnarulex and Trastuzumab Deruxtecan in Patients With HER2 Expressing Solid Tumors

This phase I trial tests the safety, side effects, and best dose of pidnarulex in combination with trastuzumab deruxtecan in treating patients with breast cancer and other solid tumors that express varying levels of a protein called HER2 and that has spread from where it first started (primary site) to other places in the body (metastatic), that cannot be removed by surgery (unresectable), or that has spread to nearby tissue or lymph nodes (locally advanced). Pidnarulex is an enzyme inhibitor that causes cell death and prevents tumor cell growth. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Giving pidnarulex in combination with trastuzumab deruxtecan may be safe, tolerable and/or effective in treating patients with metastatic, unresectable, or locally advanced HER2-expressing breast cancer or other solid tumors.

Start Date05 Oct 2026

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Fam-trastuzumab deruxtecan-NXKI

100 Translational Medicine associated with Fam-trastuzumab deruxtecan-NXKI

100 Patents (Medical) associated with Fam-trastuzumab deruxtecan-NXKI

1,154

Literatures (Medical) associated with Fam-trastuzumab deruxtecan-NXKI

01 Jul 2026·Respiratory Investigation

Response to trastuzumab deruxtecan in postoperative recurrent lung adenocarcinoma harboring concurrent EGFR and HER2 mutations after progression on adjuvant osimertinib

Article

Author: Muramoto, Kei ; Naito, Daiki ; Goebuchi, Kageaki ; Fukushima, Kazuaki ; Furukawa, Tsuguhiro ; Akaike, Kimitaka ; Saruwatari, Koichi ; Tomita, Yusuke ; Sakagami, Takuro ; Nishiyama, Taketaka ; Okabayashi, Hiroko

Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) mutations are key molecular targets in non-small cell lung cancer (NSCLC). We report a rare case of postoperative recurrent lung adenocarcinoma in an 84-year-old woman harboring EGFR L858R and HER2 S310F mutations after progression on adjuvant osimertinib. After further progression on chemotherapy, she received trastuzumab deruxtecan (T-DXd), which induced metastatic regression and yielded disease control for approximately 6 months. This case highlights a therapeutic approach for NSCLC with multiple driver alterations and demonstrates the clinical activity of T-DXd in osimertinib-refractory EGFR-mutant disease with a concurrent HER2 alteration.

01 Jul 2026·Value in Health Regional Issues

Budget Impact Analysis of Fam-Trastuzumab-Deruxtecan as a Second Line in Patients With HER2-Positive Metastatic Breast Cancer in Oman

Article

Author: Aljaber, Rana ; Al Froukh, Rawan F ; Al Hashar, Amna

OBJECTIVES:

Despite advancements, breast cancer remains a major global health and financial challenge. Trastuzumab-based therapies, particularly Fam-Trastuzumab-Deruxtecan (T-DXd), have shown superior outcomes, leading to its recommendation as a preferred second-line treatment. However, its high cost necessitates a budget impact analysis (BIA) to evaluate financial feasibility. This study assesses the 1-year budget impact of replacing Trastuzumab Emtansine (TDM1) with T-DXd for HER2+ metastatic breast cancer in an Omani cancer center.

METHODS:

A static BIA model was built based on National Institute for Health and Care Excellence template with adaptation as required. The model time horizon was 1 year then projected over another 2 years, using 2022 as the baseline year, adopting Omani healthcare-payer perspective. The analysis considered 2 scenarios: (1) TDM1 as the current formulary drug and (2) T-DXd is introduced instead of TDM1, assuming that treatment share would be 100%. One-way sensitivity analysis is performed to assess the model's robustness.

RESULTS:

The BIA demonstrated that replacing TDM1 with T-DXd for the eligible patients would lead to increase in the budget expenditure. Over a 3-year period, considering the provided assumptions and input data, the cumulative excess amount to €5 909 481.67. The primary contributing factors are the drug acquisition cost and the median treatment duration. The sensitivity analysis results suggest the model is robust to changes in adverse drug reaction costs, unlike changes in treatment duration and drug cost.

CONCLUSIONS:

Although T-DXd improves clinical outcomes, its adoption as a second-line treatment in Oman poses a substantial financial burden, necessitating careful budget planning to ensure long-term affordability.

01 Jun 2026·BREAST

Antibody–drug conjugate sequencing in HER2-positive metastatic breast cancer: Real-world outcomes of trastuzumab deruxtecan with and without prior T-DM1 exposure

Article

Author: Bayram, Ertuğrul ; Deliktaş Onur, İlknur ; Yeşil Çınkır, Havva ; Majidova, Nargiz ; Gündüz, Şeyda ; Erdem, Dilek ; Karadurmuş, Nuri ; Er, Özlem ; Selçukbiricik, Fatih ; Başaran, Gül ; Güney, Bünyamin ; Gürsu, Rıza Umar ; Kalem, Ali ; Oruç, Ahmet ; Tünbekici, Salih ; Seyyar, Mustafa ; Güren, Ali Kaan ; Ateş, Öztürk ; Köylü, Bahadır ; Yazıcı, Melike ; Türker, Sema ; Güney, Gizem ; Akdoğan, Orhun ; Araz, Murat ; Göker, Erdem ; Kaban, Kerim ; Yılmaz, Mesut ; Aykan, Musa Barış ; Demir, Nazan ; Yıldız, İbrahim ; Molinas Mandel, Nil ; Kıkılı, Cevat İlteriş ; Biter, Sedat ; Korkmaz, Taner ; Çabuk, Devrim ; Tunalı, Didem ; Bilici, Ahmet ; Laçin, Şahin ; Sezer, Ahmet ; Altunok, Oğuz ; Şahin, Taha Koray ; Bayoğlu, İbrahim Vedat ; Çelik, Emir ; Aksoy, Sercan ; Açıkel Yüksel, Sakine Damla ; Ekinci, Ömer Burak ; Kemik, Fatih ; Özçelik, Hakan ; Güven, Deniz Can ; Yazıcı, Ozan ; Tural, Deniz

BACKGROUND:

Optimal sequencing of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in HER2 positive metastatic breast cancer (mBC) remains uncertain, and real-world evidence on the impact of prior T-DM1 exposure on subsequent T-DXd outcomes is limited.

METHODS:

We conducted a multicenter, retrospective cohort study across 21 oncology centers in Türkiye including consecutive adults with HER2 positive mBC who received at least one cycle of T-DXd between 2020 and 2025. Patients were classified as T-DM1 pretreated or T-DM1 naive at T-DXd initiation. The primary endpoint was progression free survival (PFS); secondary endpoints included objective response rate (ORR), duration of response (DOR), and overall survival (OS). To address confounding by indication, we applied stabilized inverse probability of treatment weighting (IPTW) based on prespecified clinical covariates and assessed covariate balance using standardized mean differences.

RESULTS:

Among 218 patients treated with T-DXd, 137 (62.8%) had received prior T-DM1 and 81 (37.2%) were T-DM1 naive. The ORR was 71.9%, including 15.2% complete and 56.7% partial responses. Median DOR in the overall cohort was 20.96 months (95% CI, 15.71-26.22). In the IPTW-weighted analysis, prior T-DM1 exposure was associated with significantly shorter PFS: 12.1 months (95% CI, 10.3-20.5) versus 26.0 months (95% CI, 18.9 - not reached) in T-DM1 naive patients (IPTW-weighted log-rank p = 0.006). Prior T-DM1 remained independently associated with higher progression risk (HR 1.99, 95% CI 1.09 - 3.62; p = 0.02). Median OS was 18.9 months (95% CI, 17.2-not reached) in T-DM1 pretreated patients and not reached in T-DM1 naive patients; the IPTW-weighted OS hazard ratio did not reach statistical significance (HR 1.80, 95% CI 0.86-3.79; p = 0.12).

CONCLUSIONS:

Trastuzumab deruxtecan demonstrated substantial real-world activity after prior T-DM1 exposure, but PFS was significantly shorter compared with T-DM1 naive patients, even after rigorous adjustment for measured confounding. These findings highlight the clinical relevance of antibody drug conjugate sequencing and support prospective studies to define the optimal positioning of T-DXd in HER2 positive mBC treatment algorithms.

1,148

News (Medical) associated with Fam-trastuzumab deruxtecan-NXKI

04 Jun 2026

·www.biopharmadive.com

A Spanish biotech banks $87M to make differentiated ADCs

Barcelona-based biotechnology startup Ona Therapeutics announced Thursday it raised an $86.6 million Series B round to launch a pair of antibody-drug conjugates into clinical development for breast and colorectal cancers.Antibody-drug conjugates, or ADCs, are now a pillar of cancer care. More than 20 are approved for different tumor types, and some are now working their way into earlier treatment lines, where they might be able to supplant traditional chemotherapy. AstraZeneca and Daiichi Sankyos Enhertu, for example, is now a multibillion-dollar seller available in multiple breast cancer settings. Many others that are available or in development are aiming for similarly expansive use.Newer biotechs aiming to break into the field are trying to improve the technology in one way or another. Some are working with proprietary linkers that connect an ADCs targeting molecule to its toxic payload. Others are delivering different types of tumor-killing molecules, or simultaneously homing in on multiple targets.Ona is instead focusing on new targets it believes can help address drug resistance, a strategy CEO Valerie Vanhooren says might be able to help those who havent responded to other therapies.Vanhoorens team initially looked to monoclonal antibodies to find these kinds of drugs, but found they werent potent enough to eliminate the treatment-resistant tumors they hoped to pursue. Ona then turned to ADCs instead, specifically searching for targets expressed in cancer cells but barely detectable in healthy tissue, she said.If we can tackle those cells responsible for resistance, you can have a deeper response and you can give these patients a longer quality of life, Vanhooren told BioPharma Dive.Valerie Vanhooren is the CEO of Ona Therapeutics.Permission granted by Ona TherapeuticsThe biotech is initially developing its lead asset, dubbed ONA-255, in the third-line setting in breast cancers that are hormone receptor-positive but negative for the protein HER2. These slow-growing tumors make up more than 70% of metastatic breast cancer cases. And while patients can get different types of hormone therapies and targeted medications called CDK 4/6 inhibitors to slow progression and hold disease in check, there are few drug options afterwards.There are not novel targets and not novel treatments there, Vanhooren said.Ona hasnt disclosed the target for ONA-255. But its same one a second preclinical prospect, a colorectal cancer treatment called ONA-389, homes in on. The company expects to advance its first drug into human studies in the near future, but didnt give an estimated timeframe.[Onas] work on cancer resistance and metastasis addresses one of the most important challenges in oncology, said Jose Mesa, a partner at Columbus Venture Partners, in a statement. Columbus co-led the Series B round with Mrieux Equity Partners, and they were joined by eight other investment firms.Ona launched with 30 million, or about $34 million, in a Series A round announced in 2020. Among its board members are Antoine Yver, a former AstraZeneca and Daiichi Sankyo executive who helped develop Enhertu, and Pamela Klein, a veteran of Genentech who led development of cancer drugs like Herceptin and Rituxan. '

ADC

01 Jun 2026

·www.prnewswire.com

Paradigm Health Implements New Clinical Trial Solution to Support Observational Study Presented at ASCO

Paradigm Health's Scalable Platform for Integrated Research and Evidence (SPIRE) helps trial sponsors generate high-quality clinical trial data across community healthcare practices Columbus, Ohio and CHICAGO, June 1, 2026 /PRNewswire/ -- Paradigm Health today announced its role in the execution of a multicenter, hybrid, observational post-marketing commitment study in the United States evaluating an FDA-approved therapy in patients with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 3+ solid tumors. The trial uses Paradigm Health's SPIRE model as the technology-enabled infrastructure to accelerate end-to-end trial operations, from trial design, site selection, patient identification, and data collection, to efficient evidence generation. A principal investigator from Florida Cancer Specialists & Research Institute (FCS) presented a poster on the trial design and operations at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting on June 1. The abstract (TPS11202) is titled A pragmatic, hybrid observational study evaluating the effectiveness of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 3+ solid tumors: DESTINY-PanTumor04. Study authors also include researchers from Paradigm Health, AstraZeneca (trial sponsor), and Daiichi Sankyo. The SPIRE infrastructure uses the same data collection technology that underpins the proof-of-concept currently underway with the U.S. Food & Drug Administration (FDA) to evaluate the implementation of Real-Time Clinical Trials. The trial was designed to track approximately 100 patients at up to 30 U.S. locations, from community practices to academic medical centers. The SPIRE model provides the end-to-end infrastructure that can help sponsors design pragmatic trials and embed into study sites to automate data collection, identify eligible patients faster, and expedite transmission of analysis-ready data to sponsors. By streamlining these labor-intensive steps, SPIRE enables researchers across community settings, hospitals, and academic medical centers to participate in the same late-phase clinical trials. "This research shows how SPIRE can be used in a broad range of healthcare settings. Already, 13 community oncology centers are participating in this study," said Kent Thoelke, Founder and CEO of Paradigm Health. "By connecting fragmented clinical databases and other data sources, we can lower the operational burden for research staff while maintaining the completeness and accuracy needed by trial sponsors. This helps make clinical research feasible for more study sites, ultimately, opening research up to more patients." The poster highlights the study's pragmatic trial elements achieved through the SPIRE model, including broad eligibility criteria, routine clinical practice settings, integration of primary and secondary sources into study data collection, and pragmatic endpoints. Paradigm Health's SPIRE model optimizes the trial design, site selection, and simplification of patient identification and enrollment, improving data accuracy and completeness, all aimed at making clinical trial workflows feasible for more sites. SPIRE-enabled pragmatic prospective studies are uniquely positioned to evaluate effectiveness in routine care and enroll patient populations that are reflective of real-world healthcare settings. "Observational and late-phase studies require the technological infrastructure to operate within clinical care delivery, and my team at FCS is at the forefront of this technological modernization," said Lucio Gordan, President and Managing Physician at FCS. "Paradigm Health's SPIRE was designed to help trial sites align clinical workflows with research operations, expediting analysis-ready data capture without increasing burden on providers or site staff." About Paradigm Health Paradigm Health has engineered an AI-powered platform to make clinical trials more accessible and efficient, so that patients, researchers, and study sponsors can maximize the impact of clinical research. Incubated by ARCH Venture Partners and backed by leading healthcare and life sciences investors, Paradigm Health aims to break down barriers across the trial ecosystem through one seamless infrastructure implemented at healthcare provider organizations, bringing potentially life-saving therapies to patients faster. For more information, visit . About SPIRE Scalable Platform for Integrated Research and Evidence (SPIRE) is an end-to-end, technology-enabled alternative to traditional CRO-led approaches for prospective, pragmatic studies, particularly for approved products and products nearing approval with established safety profiles. The solution combines: EHR-integrated technology embedded directly into patient visits, in community, rural, and academic settings across 46 of 50 states Data-driven study design and site selection informed by care patterns and site capabilities Full-service study conduct support across site selection, startup, enrollment, data management, safety, and closeout SPIRE Intended Use Cases SPIRE is intended for prospective, pragmatic U.S. studies for assets that are approved of nearing approval, including: Post-marketing requirements and commitments with observational designs Phase IV safety and/or effectiveness Label expansion Comparative effectiveness Prospective registries and external control arms Hybrid studies incorporating randomized and pragmatic elements About Paradigm Health's Collaboration with FDA on Real-Time Clinical Trials In April 2026, Paradigm Health announced a landmark research collaboration with the FDA focused on advancing a new model to accelerate clinical trial execution and regulatory review. The model uses Paradigm Health's technology-enabled Study Conduct platform to allow real-time review by the FDA, by automating data collection and analysis, and streamlining the reporting of key safety and efficacy signals to trial sponsors and the FDA. SOURCE Paradigm Health, Inc. 21% more press release views with Request a Demo

Clinical StudyImmunotherapyASCO

01 Jun 2026

·www.biospace.com

Callio Therapeutics to Present Phase 1 Trial Design of CLIO-8221, Novel Dual-Payload ADC, at ASCO 2026

SEATTLE and SINGAPORE, May 27, 2026 (GLOBE NEWSWIRE) -- Callio Therapeutics, a biotherapeutics company advancing dual-payload antibody-drug conjugates (ADCs) with a targeted, multi-mechanism approach to cancer treatment, today announced that it will present a trial-in-progress poster highlighting the Phase 1 trial design of CLIO-8221 at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting (May 29-June 2) in Chicago. CLIO-8221 is a first-in-class dual-payload ADC currently in Phase 1 clinical development ( NCT07300943 ) for HER2-expressing solid tumors. “CLIO-8221 is the first program from Callio Therapeutics’ dual-payload ADC pipeline to enter the clinic, advancing our strategy to develop rationally designed payload combinations for hard-to-treat tumors,” said Naomi Hunder, MD, Chief Medical Officer of Callio Therapeutics. “Developed with our proprietary linker technology and payload combination platform, CLIO-8221 is a first-in-class dual-payload ADC designed to deliver a topoisomerase 1 inhibitor and an ATR inhibitor directly to HER2-expressing tumors to address key mechanisms of resistance to existing HER2-targeted ADCs, including trastuzumab deruxtecan. With our Phase 1 trial now enrolling patients with advanced HER2-expressing solid tumors, we look forward to generating clinical data that will inform its potential as a differentiated treatment option.” “Patients with HER2-expressing solid tumors who progress on currently available HER2-targeted therapies continue to have limited treatment options,” said Timothy A. Yap, MBBS, PhD, lead investigator at The University of Texas MD Anderson Cancer Center for the CLIO-8221 Phase 1 trial, and presenting author of the poster. “CLIO-8221 represents an innovative dual-payload approach to overcome resistance associated with existing HER2-targeted ADCs. This trial marks an important step in evaluating whether combining topoisomerase 1 and ATR inhibition within a single HER2-targeted ADC can expand treatment possibilities for patients with HER2-expressing solid tumors.” The Phase 1 clinical trial recruitment is ongoing in Australia and the United States, and the company plans to activate sites in China. At ASCO, Callio Therapeutics will present previously disclosed preclinical data (AACR 2026) that support the therapeutic potential of CLIO-8221 and the Phase 1 trial design: By simultaneously delivering a topoisomerase 1 inhibitor (exatecan) and an ATR inhibitor (berzosertib), CLIO-8221 drives direct tumor cell killing at doses that also support a robust bystander effect, achieving superior in vivo efficacy compared to single-payload ADCs CLIO-8221 demonstrated potent anti-tumor activity across varying HER2 expression levels and drove tumor regression after a single dose in both trastuzumab deruxtecan-sensitive and -insensitive models CLIO-8221 exhibited a highly favorable safety profile; it was well-tolerated in non-human primates with no significant adverse effects observed at doses of 70 mg/kg (highest dose tested), establishing a No-Observed-Adverse-Effect Level (NOAEL) significantly higher than that of trastuzumab deruxtecan Phase 1 of the study is a dose escalation with optional dose level expansions, and dose escalation may enroll across HER2-expressing cancers, including cancers that did not respond to or relapsed after trastuzumab deruxtecan treatment Presentation details: Poster/Abstract Title: Phase 1/2 Study of CLIO-8221, a HER2-targeted, dual-payload exatecan and ATR inhibitor antibody-drug conjugate (ADC) in patients with advanced HER2-expressing solid tumors Poster Session : Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology Date & Time : May 30, 2026, 1:30 PM - 4:30 PM CDT Location: McCormick Place, Hall A – Posters and Exhibits Presenter : Timothy A. Yap, MBBS, PhD, The University of Texas MD Anderson Cancer Center Abstract Number: TPS3162 Poster Board: 295b The full abstract is available on the ASCO Annual Meeting website. The poster will be available on the ASCO website on May 30, 2026. About CLIO-8221 HER2 is a clinically validated target for antibody-drug conjugates (ADCs), with multiple approved therapies demonstrating meaningful benefit across tumor types, however, most patients eventually progress on treatment despite retaining HER2 expression. Mechanistic resistance to cytotoxic payloads has emerged as a key reason for treatment failure. CLIO-8221 is a novel, first-in-class dual-payload ADC targeting HER2, designed to address this challenge. CLIO-8221 delivers two mechanistically complementary payloads, a topoisomerase 1 (Topo1) inhibitor and an ATR inhibitor, directly to HER2-expressing tumors. While Topo1 inhibitors have shown strong clinical activity, activation of the DNA damage response following Topo1 inhibitor-induced replication stress represents a potential major driver of resistance. By simultaneously inhibiting Topo1 and blocking the DNA damage response through ATR inhibition, CLIO-8221 is engineered to overcome payload insensitivity and sensitize tumors to Topo1 inhibition. Developed using proprietary linker and ADC platform technologies, CLIO-8221 aims to maximize anti-tumor activity while reducing systemic toxicity, offering the potential for deeper and more durable responses in patients who have progressed on existing HER2-targeted therapies. About Callio Therapeutics Callio Therapeutics is a clinical‑stage company engineering oncology-focused dual-payload ADCs for the next frontier of targeted cancer therapy. Powered by a proprietary platform featuring adaptable, modular linker technology, Callio Therapeutics is developing a focused pipeline of dual-payload ADCs engineered with rational, synergistic payload combinations matched to specific tumor biology and to counter multiple mechanisms of resistance. CLIO-8221, the company’s lead candidate, is a HER2-targeted dual-payload ADC currently being evaluated in a Phase 1 clinical trial. Callio Therapeutics is built on technology and programs licensed from Hummingbird Bioscience, an AI-enabled biotherapeutics company and R&D collaborator. Headquartered in Seattle and Singapore, and backed by top life science investors, Callio Therapeutics is built to discover and deliver, with an experienced team with a track record of success. For more information, visit and follow Callio Therapeutics on LinkedIn. Contacts Media: Crystal Ho media@calliotx.com Ally Stubin – ICR Healthcare Ally.Stubin@ICRHealthcare.com (646) 667-1861 Investors: ir@calliotx.com Stephanie Carrington – ICR Healthcare stephanie.carrington@ICRHealthcare.com (646) 277-1282

Phase 1ASCOADCAACR

100 Deals associated with Fam-trastuzumab deruxtecan-NXKI

External Link

KEGG	Wiki	ATC	Drug Bank
-	Fam-trastuzumab deruxtecan-NXKI	L01XC	DB14962

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Metastatic human epidermal growth factor 2 positive carcinoma of breast	United States	Daiichi Sankyo, Inc.	15 May 2026
Stomach Cancer	India	AstraZeneca PLC	07 Oct 2025
HER2 Positive Solid Tumors	United Kingdom	Daiichi Sankyo UK Ltd.	09 Apr 2025
HR-positive/HER2-low Breast Carcinoma	United States	Daiichi Sankyo Co., Ltd.	28 Jan 2025
Hormone receptor positive HER2 positive breast cancer	South Korea	Daiichi Sankyo Co., Ltd.	19 Sep 2022
HER2 mutant non-small cell lung cancer	United States	Daiichi Sankyo, Inc.	11 Aug 2022
HER2 Positive Stomach Adenocarcinoma	Australia	AstraZeneca Pty Ltd.	08 Oct 2021
HER2-Low Breast Carcinoma	Australia	AstraZeneca Pty Ltd.	08 Oct 2021
Metastatic breast cancer	Canada	AstraZeneca Canada, Inc.	15 Apr 2021
HER2 positive Gastroesophageal Junction Adenocarcinoma	United States	Daiichi Sankyo, Inc.	15 Jan 2021
HER2-positive gastric cancer	Japan	Daiichi Sankyo Co., Ltd.	25 Sep 2020
HER2 Positive Breast Cancer	United States	Daiichi Sankyo, Inc.	20 Dec 2019

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Phase 3	United States	Daiichi Sankyo, Inc.	23 Dec 2025
Solid tumor	Phase 3	China	Daiichi Sankyo, Inc.	23 Dec 2025
Solid tumor	Phase 3	Japan	Daiichi Sankyo, Inc.	23 Dec 2025
Solid tumor	Phase 3	Australia	Daiichi Sankyo, Inc.	23 Dec 2025
Solid tumor	Phase 3	Brazil	Daiichi Sankyo, Inc.	23 Dec 2025
Solid tumor	Phase 3	France	Daiichi Sankyo, Inc.	23 Dec 2025
Solid tumor	Phase 3	Israel	Daiichi Sankyo, Inc.	23 Dec 2025
Solid tumor	Phase 3	Italy	Daiichi Sankyo, Inc.	23 Dec 2025
Solid tumor	Phase 3	South Korea	Daiichi Sankyo, Inc.	23 Dec 2025
Solid tumor	Phase 3	Spain	Daiichi Sankyo, Inc.	23 Dec 2025

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04622319 (DESTINY-Breast05, ASCO2026)	Phase 3	HER2 Positive Breast Cancer Adjuvant HER2+	1,619	trastuzumab deruxtecan (T-DXd) 5.4 mg/kg	ochgylrgbd(kwewwbrdal) = xldoyjzvsi exfaqreafu (gdtrmvedio ) View more	Positive	29 May 2026
				trastuzumab emtansine (T-DM1) 3.6 mg/kg	ochgylrgbd(kwewwbrdal) = kjeujsqynp exfaqreafu (gdtrmvedio ) View more
ASCO2026	Early Phase 1	Advanced Colorectal Adenocarcinoma	289	ADCs (indusatumab vedotin, labetuzumab govitecan, trastuzumab deruxtecan, precemtabart tocentecan)	omsbnjlyyy(zszlgvblwk) = ookvlhfdsz mpzitrbdqk (avxfkpxtpl, 3.7 - 16.4) View more	Positive	29 May 2026
JPRN-jRCT2011210017 (MYTHOS, ASCO2026)	Phase 2	Salivary gland cancer recurrent HER2-low	36	Trastuzumab deruxtecan 5.4 mg/kg	qonxzorioh(mcjhijlnoy) = wjfjredkpm yjhhkfuhit (pgxptcnazh, 23.1 - 56.5) View more	Negative	29 May 2026
				Trastuzumab deruxtecan 5.4 mg/kg (salivary duct carcinoma)	qonxzorioh(mcjhijlnoy) = nybhqymgmi yjhhkfuhit (pgxptcnazh, 28.3 - 65.7)
ASCO2026	Not Applicable	Advanced breast cancer	82	trastuzumab deruxtecan	rahtjxvjvu(abqsdgiqlt) = lacgqcjgva qzdnwjqjdc (ajumfvpzso ) View more	Positive	29 May 2026
				trastuzumab emtansine	rahtjxvjvu(abqsdgiqlt) = uvfgphxdre qzdnwjqjdc (ajumfvpzso )
NCT04494425 (DESTINY-Breast06, ASCO2026)	Phase 3	Metastatic human epidermal growth factor 2 positive carcinoma of breast	49	trastuzumab deruxtecan (Adherent to ILD/pneumonitis TMGs)	rfvobruihf(psvrounhkt) = naswhzhffg undjoaiopl (bszvupqrqa ) View more	Positive	29 May 2026
				trastuzumab deruxtecan (Partially adherent to ILD/pneumonitis TMGs)	rfvobruihf(psvrounhkt) = hudewjvzmq undjoaiopl (bszvupqrqa ) View more
ASCO2026	Not Applicable	Metastatic Malignant Neoplasm to the Leptomeninges HER2 positive \| ER positive \| PR positive	16	Trastuzumab-deruxtecan	hupmghnhfk(kedpsuhgxd) = debvcueqza jxaufjrrzp (ndvvxvfpws, 2.7 - 12.0) View more	Positive	29 May 2026
LC-SCRUM-Asia (ASCO2026)	Not Applicable	HER2-positive Non-squamous non-small cell lung cancer HER2 exon 20 insertion-positive	77	HER2-TKI-naïve patients	jzjtxuravy(pzcynpkhzf) = qsdqtttmgl hnbuluvfcu (sewystsgns ) View more	Positive	29 May 2026
				those treated with selective HER2-TKIs (zongertinib or severtinib)	jzjtxuravy(pzcynpkhzf) = ibdgxzjdku hnbuluvfcu (sewystsgns ) View more
NCT04379596 (DESTINY-Gastric03 (DG-03), ASCO2026)	Phase 1/2	Adenocarcinoma of Esophagus \| HER2-expressing Gastric Adenocarcinoma \| Gastroesophageal junction adenocarcinoma First line HER2-expressing	137	T-DXd 6.4 mg/kg + pembrolizumab + fluoropyrimidine	vdqjxycino(aymnupxlyp) = ocknrfpcsd vidftpcwsa (oevaitmdqe ) View more	Positive	29 May 2026
				T-DXd 5.4 mg/kg + pembrolizumab + fluoropyrimidine	vdqjxycino(aymnupxlyp) = gufoxfkxqj vidftpcwsa (oevaitmdqe ) View more
NCT06819007 (DESTINY-Ovarian01, ASCO2026)	Phase 3	First line \| Maintenance HER2-expressing	21	T-DXd + BEV	fnivsfocat(npuguqcboa) = synqtynaei kotqlclnej (xaqbprsgwi ) View more	Positive	29 May 2026
ASCO2026	Not Applicable	Metastatic breast cancer HER2-positive \| HER2-low	406	Trastuzumab deruxtecan	hitceuxwtk(tjqbwkuiin) = axsclpqbhp ckicjnzalo (kanwapblpm ) View more	Positive	29 May 2026

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