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

HER2 Positive Solid TumorsHR-positive/HER2-low Breast CarcinomaHormone receptor positive HER2 positive breast cancer+ [62]

Inactive Indication

Meningeal Carcinomatosis

Originator Organization

Daiichi Sankyo Co., Ltd.

Active Organization

Daiichi Sankyo Co., Ltd.

AstraZeneca PLC

AstraZeneca Investment (China) Co. Ltd.

+ [8]

Inactive Organization

Daiichi Sankyo Taiwan Ltd.

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

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

Structure/Sequence

Boost your research with our ADC technology data.

view full example data

Sequence Code 18481L

Source: *****

Sequence Code 44772H

Source: *****

154

Clinical Trials associated with Fam-trastuzumab deruxtecan-NXKI

NCT06899126

/ Not yet recruitingPhase 3

A Phase 3, Multicenter, Randomized, Open-label Trial of Trastuzumab Deruxtecan in Combination With Pembrolizumab Versus Platinum-based Chemotherapy in Combination With Pembrolizumab, as First-line Therapy in Participants With Locally Advanced Unresectable or Metastatic HER2 Overexpressing and PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer (DESTINY-Lung06)

This clinical trial is designed to assess the efficacy and safety of trastuzumab deruxtecan (T-DXd; Enhertu®) in combination with pembrolizumab versus platinum-based chemotherapy in combination with pembrolizumab in participants with no prior therapy for locally advanced unresectable or metastatic non-squamous NSCLC, whose tumors have HER2-overexpressing and PD-L1 TPS <50% without known AGA that have locally available therapies targeting their AGAs in first-line advanced/metastatic setting.

Start Date07 Sep 2025

Sponsor / Collaborator

Daiichi Sankyo Co., Ltd.

[+1]

NCT07022483

/ Not yet recruitingPhase 3

A Phase 3, Multicenter, Randomized, Open-label Trial of Trastuzumab Deruxtecan Versus Standard of Care Chemotherapy With or Without Radiotherapy as Adjuvant Treatment for HER2-Expressing (IHC 3+/2+) Endometrial Cancer (DESTINY-Endometrial02/ GOG-3122/ ENGOT-en30/GINECO)

This study is designed to assess efficacy and safety of T-DXd adjuvant therapy, with or without radiotherapy, post-surgery in anticancer treatment naïve (including neoadjuvant therapy) endometrial cancer with various HER2 expression levels.

Start Date25 Aug 2025

Sponsor / Collaborator

Daiichi Sankyo Co., Ltd.

[+1]

NCT06680596

/ Not yet recruitingPhase 2IIT

A ctDNA Screening Program in Patients With HR+, HER2 Low Metastatic Breast Cancer for Detection of High-risk Relapse Patients on Any CDK4/6 Inhibitor Followed by a Single Arm Phase II Trial of Trastuzumab-deruxtecan in Patients With Persistent ctDNA After 1 Month of Treatment With Endocrine Therapy Combined With CDK4/6 Inhibitor

After an initial screening phase to identify patients with persistent blood circulating DNA tumors, patients will be enrolled in the treatment phase that was designed as an open-label, multicentre, phase II study, to test the efficacy of trastuzumab deruxtecan in terms of progression-free survival (PFS).

Start Date30 Jul 2025

Sponsor / Collaborator

UNICANCER

[+2]

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

820

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

31 Dec 2025·Human Vaccines & Immunotherapeutics

Cost-effectiveness of trastuzumab deruxtecan as a second-line treatment for HER2-mutant advanced non-small cell lung cancer

Article

Author: You, Shuhui ; Gong, Caifeng ; Cai, Qi ; Zhang, Wen ; Huang, Jinglong ; Zhou, Aiping

The study of DESTINY-Lung01 and DESTINY-Lung02 demonstrated the favorable efficacy and optimal dosage of trastuzumab deruxtecan (T-DXd) in managing the human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) patients who had received previous treatment. The study sought to assess the cost-effectiveness of T-DXd in both the United States (US) and Chinese healthcare systems. Markov models were developed to evaluate the overall cost, incremental cost-effectiveness ratio (ICER), quality-adjusted life years (QALYs), and life years (LYs) of treatment with T-DXd compared with docetaxel, nivolumab, and pyrotinib for patients in the US and China. The level of willingness-to-pay (WTP) in the US and China is 150,000/QALYs and 32,517/QALYs, respectively. Sensitivity analyses were carried out to ensure the precision of the model. T-DXd yielded additional QALYs of 0.63 and 0.06 with an ICER of $338997.84 and $1437258.33 per QALY, respectively, in the US compared to the docetaxel and nivolumab regimens. And T-DXd yielded additional QALYs of 0.63, 0.06, and 0.13 with an ICER of $137959.45, $623805.93, and $515447.12 per QALY, respectively, in China compared to the docetaxel, nivolumab, and pyrotinib regimens. Sensitivity analysis showed that the cost of drugs is the most influential factor. T-DXd provides substantial therapeutic benefit for NSCLC patients with HER2 mutations who have had previous treatment but is not deemed cost-effective in either the US or China when compared to docetaxel, nivolumab, and pyrotinib. Price reduction is perhaps the main way to make T-DXd cost-effective.

01 Sep 2025·CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Adverse effect of trastuzumab deruxtecan in solid tumours: A systematic review and meta-analysis

Review

Author: Mittal, Abhenil ; Kumar, Vikaash ; Pathak, Neha ; Berner-Wygoda, Yael ; Savill, Jacqueline ; Gimenez, Diego Malon ; Di Iorio, Massimo ; Aljuhani, Amal ; Amir, Eitan

INTRODUCTION:

Trastuzumab deruxtecan (T-DXd) is approved for use in solid tumours. Here we summarize its safety and tolerability profile.

METHODS:

Studies were identified from MEDLINE and EMBASE and recent proceedings. Analysis comprised clinical trials (phases 1 [dose-expansion], 2 or 3) reporting safety and tolerability of T-DXd. Data were pooled as the mean weighted by individual study sample size from single arm studies. Randomized studies were analyzed separately to compare T-DXd to chemotherapy and to trastuzumab emtansine. Meta regression comprised linear regression weighted by sample size was performed.

RESULTS:

A total of 35 studies with 48 distinct cohorts were included in the analysis. All grade adverse effects (AEs) and grade ≥3 AEs were 97.2% and 54.9% respectively. Most common all grade AEs included: nausea (66.2%), fatigue (41.8%) and anemia (33.8%). Common grade ≥3 AEs included anemia (12.9%), thrombocytopenia (6.7%) and fatigue (5.3%). Pooled incidence rate of interstitial lung disease (ILD) and grade≥3 ILD were 13.2% and 2.3% respectively, and 2% had febrile neutropenia. Cardiotoxicity was rare. Treatment- and ILD- related deaths were reported in 5% and ILD 1.4%, respectively. Compared to chemotherapy, T-DXd had higher odds of AEs and treatment discontinuation. Higher dose, non-Caucasian ethnicity and cancer sites other than breast were associated with grade ≥3 AE, grade ≥3 ILD, AE- and ILD- related deaths and serious AEs.

CONCLUSIONS:

T-DXd has a safety and tolerability profile less favourable than classical chemotherapy. Dose, ethnicity and cancer site are associated with worse safety and tolerability.

02 Jun 2025·CANCER RESEARCH

Perivascular Niche–Resident Alveolar Macrophages Promote Interstitial Pneumonitis Related to Trastuzumab Deruxtecan Treatment

Article

Author: Yang, Yuxuan ; Yang, Teng ; Wang, Fei ; Xue, Xiru ; Li, Meng ; Fan, Mengyang ; Ying, Jieer ; Zhu, Jiayu ; Zhu, Xiu ; Yu, Chuanfei ; Shimura, Takaya ; Zhang, Ziwen ; Guo, Peng ; Cao, Zhiwei ; Xing, Yun ; Zhang, Yuchao ; Tian, Xuefei ; Fang, Jianmin ; Wei, Qing ; Li, Yuanzheng ; Lu, Ye ; Cheng, Xiangdong ; Wang, Lan

Abstract:

Trastuzumab deruxtecan (T-DXd) is a transformative HER2-targeting antibody–drug conjugate (ADC) for treating breast cancer. Unfortunately, T-DXd has also been implicated in causing fatal interstitial lung disease (ILD) in multiple clinical trials. A better understanding of the mechanistic basis of these ADC-induced adverse effects could enable development of strategies to prevent or treat T-DXd–related ILD. In this study, we determined that T-DXd–induced ILD represents an off-target adverse event rather than an on-target off-tumor adverse event. To further investigate this phenomenon, an immunocompetent murine model that recapitulates T-DXd–induced ILD events was developed, facilitating in-depth mechanistic studies. Single-cell RNA sequencing in this model implicated alveolar macrophages (AM) as the primary cell type impacted by T-DXd in the lung microenvironment. Intravital microscopy further revealed that AMs resident in perivascular niches directly engulfed blood-circulating T-DXd via Fc–FcγR engagement. This Fc–FcγR interaction with T-DXd triggered a phenotypic shift in AMs from an immunosuppressive to a pro-ILD state, characterized by inflammation and immune activation, mediated through the SPP1 pathways. Finally, mitigating nonspecific T-DXd uptake in the lung by preconditioning perivascular AMs with IgG1 or the parental antibody of T-DXd significantly reduced unintended ADC absorption. These findings elucidate a mechanism by which T-DXd ignites the lung immune microenvironment and underscore the importance of off-target endocytosis by innate immune cells in the development of ADC-related toxicities.Significance: Preconditioning the perivascular niche can prevent lung inflammation induced by antibody-drug conjugate phagocytosis by alveolar macrophages and subsequent SPP1high macrophage differentiation, providing a clinically viable strategy for mitigating interstitial lung disease.

823

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

14 hours ago

·www.einpresswire.com

Unlocking Precision in Oncology: Antibody-Drug Conjugates (ADCs) Redefine Cancer Therapy | Competitive Intelligence

Antibody-drug conjugates (ADCs) are revolutionizing cancer care by combining precision targeting with potent cytotoxins, offering hope for hard-to-treat tumors. ADCs are transforming cancer therapy-uniting accuracy with lethal efficacy, they offer a beacon of hope for patients with limited treatment options and challenging malignancies.” — DataM Intelligence AUSTIN, TX, UNITED STATES, June 17, 2025 / EINPresswire.com / -- Antibody-Drug Conjugates (ADCs): A New Era in Precision Cancer Treatment The oncology world is undergoing a revolutionary transformation—and at the heart of this transformation are Antibody-Drug Conjugates (ADCs). These sophisticated drugs marry the pinpoint targeting abilities of monoclonal antibodies with the cell-killing power of chemotherapy agents. The result? A new standard of care that delivers cytotoxic therapy directly to cancer cells with reduced harm to healthy tissues. Download CI Sample Report: https://www.datamintelligence.com/strategic-insights/ci/antibody-drug-conjugates-adcs The ADC Blueprint: Three Critical Components An ADC is built from three essential elements that work in synergy to seek and destroy cancer cells: - Monoclonal Antibody (mAb): This biologic component identifies and binds to specific antigens on the surface of cancer cells. For instance, trastuzumab targets the HER2 receptor, which is overexpressed in some breast and gastric cancers. - Linker: This chemical bridge attaches the antibody to the drug. The linker must be stable in the bloodstream but easily cleaved once inside the cancer cell. Linkers come in cleavable types (triggered by pH or enzymes) and non-cleavable forms that release the drug only after cellular degradation. - Cytotoxic Payload: These are highly potent chemotherapy drugs—such as MMAE (a microtubule inhibitor) or SN-38 (a topoisomerase inhibitor)—capable of killing cells even at low concentrations. How ADCs Work: A Targeted Strike on Tumors The mechanism of ADCs is elegantly efficient: - Target Binding: The monoclonal antibody binds specifically to a cancer-specific antigen. - Internalization: The cancer cell engulfs the ADC via receptor-mediated endocytosis. - Payload Release: Inside the cell, the linker is cleaved, releasing the cytotoxic drug. - Cell Death: The released drug disrupts critical cellular functions, triggering apoptosis (programmed cell death). This targeted strategy minimizes collateral damage to healthy tissues and reduces the side effects typically associated with traditional chemotherapy. Latest Innovations & Trends in ADC Development The field of ADCs is evolving at a breathtaking pace. Several cutting-edge trends are emerging in both preclinical and clinical research: - Smarter Linkers and Payloads: New linker designs improve stability in circulation and allow more selective release of drugs in tumor environments. Payloads are becoming more diverse, potent, and even immunomodulatory. - Multi-Antigen Targeting: Bispecific ADCs are in development to address tumors with heterogeneous antigen expression, thereby increasing efficacy. - Combination Therapies: ADCs are being trialed alongside immune checkpoint inhibitors or other modalities to amplify response rates in resistant tumors. - Enhanced Manufacturing: Better conjugation techniques, including site-specific approaches, are improving the safety, consistency, and scalability of ADC production. Approved ADCs: A Growing Class of Blockbusters As of early 2025, several ADCs have received FDA approval and are generating robust clinical and commercial outcomes: - Enhertu ® (Daiichi Sankyo/AstraZeneca): A HER2-targeting ADC approved for breast, gastric, and lung cancers. It recorded approximately $3.75 billion in sales in 2024 and is considered best-in-class for HER2-positive tumors. - Trodelvy ® (Gilead Sciences): The first Trop-2-targeting ADC for triple-negative breast cancer (TNBC) and bladder cancer. Despite its moderate toxicity, Trodelvy is a market leader with ~$1.32 billion in 2024 sales. - Adcetris ® (Seagen, now part of Pfizer): Approved since 2011, this CD30-targeting ADC is a game-changer for Hodgkin lymphoma and other hematologic malignancies. Its consistent performance places it as a top ADC brand. - Padcev ® (Seagen/Pfizer): Targeting Nectin-4, this ADC is FDA-approved for urothelial carcinoma and is known for its first-in-class status and strong market uptake. Next-Gen ADCs in the Pipeline The ADC pipeline is rich and varied, with numerous candidates expected to reach approval in the next few years: - Rinatabart Sesutecan is an advanced HER2-targeting ADC designed to offer better safety and efficacy than current standards. - Teliso-V from AbbVie is showing promise in non-small cell lung cancer (NSCLC), addressing unmet needs in difficult tumor types. - Elahere ® is approved for platinum-resistant ovarian cancer and is being developed for other solid tumors. With over 100 ADC candidates in various stages of development, the coming decade will likely witness a surge of new approvals and expanded indications. Market Size and Future Outlook In 2024, the global ADC market was valued at $13.81 billion. The market is projected to grow at a CAGR of 15–17% through 2033. This expansion is driven by: - Rising incidence of difficult-to-treat cancers. - Clinical success of FDA-approved ADCs. - Increased R&D investments from pharmaceutical and biotech companies. - Expanding indications and geographic approvals. North America leads the market, but Asia-Pacific—particularly China and South Korea—is rapidly catching up with an aggressive push in ADC research, trials, and local manufacturing. Challenges and Unmet Needs Despite their advantages, ADCs still face several hurdles: - Tumor Heterogeneity: Not all tumors express target antigens uniformly. This limits efficacy. Emerging bispecific ADCs and predictive biomarkers are potential solutions. - Drug Resistance: Tumors can evade ADC therapy by reducing antigen expression or pumping out the payload. Developers are exploring alternative payloads and combination regimens. - Off-Target Toxicity: ADCs can sometimes harm healthy cells. This is being addressed through better linkers, optimized antibody affinities, and refined dosing schedules. - Solid Tumor Penetration: Dense tumor microenvironments block ADC access. Researchers are developing smaller, nanobody-based ADCs for deeper tissue penetration. - High Costs and Complex Manufacturing: ADCs are expensive to produce and difficult to scale. Advances in conjugation technologies and the emergence of biosimilar ADCs could ease the burden. Competitive Landscape and Key Players The ADC sector is both competitive and collaborative, marked by M&A activity, strategic alliances, and innovation-led expansion: - Pfizer’s $43 billion acquisition of Seagen in 2024 solidified its leadership in the ADC space, adding Adcetris ® , Padcev ® , and Tivdak ® to its oncology portfolio. - Gilead’s $21 billion Immunomedics acquisition brought Trodelvy ® into its hands, with the company now expanding into new indications. - AstraZeneca and Daiichi Sankyo’s partnership continues to yield market-leading HER2-targeted ADCs like Enhertu ® . - AbbVie’s $10 billion investment in ImmunoGen reflects its strategic bet on next-generation ADCs for solid tumors such as NSCLC. Book Free CI Consultation Call: https://www.datamintelligence.com/strategic-insights/ci/antibody-drug-conjugates-adcs The Road Ahead: Beyond Cancer While oncology remains the primary focus, ADCs are also being explored for autoimmune and infectious diseases. Researchers are investigating ADCs that can: - Deliver immunosuppressive payloads for autoimmune diseases like lupus. - Target bacterial pathogens with precision antibiotics attached to monoclonal antibodies. Though early-stage, these developments could dramatically widen the scope of ADC applications. Conclusion: ADCs at the Frontier of Precision Medicine Antibody-drug conjugates stand as one of the most exciting innovations in modern oncology. They embody the future of precision medicine—where therapy is tailored, effective, and kinder to the patient. As the science evolves, ADCs are expected to transition from niche treatments to mainstream therapies across a broad range of cancers and beyond. Read Related CI Reports: 1. Systemic Sclerosis | Competitive Intelligence 2. Sjogren Disease | Competitive Intelligence Sai Kumar DataM Intelligence 4market Research LLP +1 877-441-4866 sai.k@datamintelligence.com Visit us on social media: LinkedIn X Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

ADCDrug ApprovalAcquisitionImmunotherapy

16 hours ago

·www.mobihealthnews.com

City of Hope study targets custom-built cancer therapies

Cancer research organization City of Hope has co-led a study to show that characterizing genetic material close to chromosomes predicts how mutated, cancer-causing genes reprogram DNA and alter the tumor microenvironment. City of Hope said the new brain cancer research provides foundational knowledge with the potential to enhance the practice of precision medicine, enabling oncologists to deliver more customized therapies to patients with cancer. A team of City of Hope researchers performed bulk RNA sequencing, tumor/normal DNA sequencing and spatial transcriptomics in a small sample of gliomas, or tumors that develop in the brain or spinal cord. Utilizing diverse experiments and validation cohorts, the team spotted common and clear-cut characteristics of the tumor microenvironment and developed an integrated analysis framework that other researchers could leverage. "Our study offers new insights into the interplay between different ecDNA," said David Craig, professor and chair of the department of integrative translational sciences at City of Hope and co-corresponding author of a study published in Nature Communications. "Importantly, when there is a prevalence of ecDNA and cancer-causing ingredients like the EGFR protein or tumor protein p53, the tumor microenvironment becomes hypoxic. It falls into a state of reduced oxygen, which has been linked to cancer progression, resistance to therapy and poor clinical outcomes," Craig said in a statement. In addition, the researchers illustrated that ecDNA propels rapid cancer cell (oncogene) proliferation outside of chromosomes, the thread-like structures inside the cell nucleus that houses DNA and RNA. EcDNA promotes the development of gliomas, genetic instability and distinct tumor cell populations within a single tumor, making cancer more challenging to eliminate. THE LARGER TREND At the 2025 American Society of Clinical Oncology Annual Meeting, City of Hope presented novel cancer treatment approaches and combinations to promote leading-edge targeted therapies and supportive care interventions that might reduce cancer risk and improve survival. Among the highlights of the data presented at the meeting is a study that supports the safety of readministering the antibody-drug conjugate trastuzumab-deruxtecan to metastatic breast cancer patients after initial drug pauses due to low-grade interstitial lung disease, which is defined as radiographic evidence of lung inflammation without associated symptoms. In 2024, ImpriMed, a precision medicine company, expanded its services to include human oncology. The aim was to provide drug-response predictions for routine blood cancers such as newly diagnosed multiple myeloma and acute myeloid leukemia. ImpriMed's human precision medicine services focus on complex blood cancers through a combination of genomic analysis, ex vivo drug sensitivity testing and machine learning. Dr. Sungwon Lim, ImpriMed CEO, said, "By empowering oncologists and researchers to leverage AI-driven technology to predict treatment outcomes, every patient can receive truly personalized therapy." In 2022, Dr. Oliver Bleck, area head of Europe South at Roche, sat down with MobiHealthNews to discuss Roche's advancements in oncology, its current work in genomics and what Roche hopes to contribute regarding personalized medicine.

ASCO

13 Jun 2025

·www.fiercebiotech.com

The trouble with TIGITs: How \'overenthusiasm\' led to Big Pharma\'s risky $6B gamble

“People went for Fc-competent [TIGITs] because it worked best in mice,” said Leerink Partners analyst Daina Graybosch, Ph.D. “They couldn\'t help themselves.\"\n Once hailed as the future of immuno-oncology, it’s been a tough few months for any remaining fans of anti-TIGIT antibodies.In April, BeOne Medicines, formerly known as BeiGene, announced it was scrapping ociperlimab over a disappointing phase 3 outlook two years after Novartis handed back the asset. Specifically, the study’s independent data monitoring committee deemed the trial unlikely to show that a combination of ociperlimab and BeOne’s own PD-1 inhibitor Tevimbra would beat Keytruda in patients with PD-L1-high non-small cell lung cancer (NSCLC).The following month brought more tough times for TIGITs, as GSK halted development of its own candidate belrestotug after deciding the iTeos Therapeutics-partnered drug in combination with anti-PD-1 inhibitor Jemperli wouldn’t score a phase 2 win in a similar NSCLC population.Even executives at Roche, whose tiragolumab appeared to buck the trend with a caveated phase 3 win in esophageal cancer in 2024, reaffirmed to Fierce Biotech earlier this year that “we stopped all of the tiragolumab trials that we could stop, and those that couldn\'t be stopped are just running out.”With Big Pharma having pumped $6 billion into this modality, what went so wrong for TIGITs?Daina Graybosch, Ph.D., a senior research analyst at Leerink Partners who covers immuno-oncology, traces the problems back to the exuberant reaction to Roche’s impressive phase 2 tiragolumab data that read out across 2020 and 2021. The Cityscape trial demonstrated that the TIGIT drug in combination with Roche’s own PD-L1 blocker Tecentriq shrank tumors in 31% of patients with metastatic lung cancer—twice as many patients as Tecentriq alone.“That\'s probably the biggest point where the field went wrong, in that they looked at this massive benefit in the small phase 2, and everybody ran after it in a parallel and broad way,” Graybosch told Fierce in an interview.“We had randomized phase 2 data from Roche, from Arcus-Gilead, from iTeos-GSK, and they all consistently showed benefit in response rate and in [progression-free survival],” she added.“I think the challenge ultimately was: How much benefit is there really? Is it enough benefit to be clinically meaningful? And are we developing the drugs in the right way, in the right format, to optimize and bring that benefit to patients?”The industry’s “overenthusiasm” for the potential of TIGITs led to a “simplistic approach” to how other companies planned to develop their own candidates, according to Graybosch.If pharmas had anticipated a “more realistic demonstration of benefit,” as seen in the failed Skyscraper-01 phase 3 study in NSCLC, “I think everybody would have developed [TIGITs] differently,” she suggested.Companies swimming in the TIGIT space have broadly fallen into two camps. Roche’s tiragolumab, along with Merck & Co.’s vibostolimab, GSK and iTeos’ EOS-448, and BeOne’s ociperlimab, are all Fc-enabled. These antibodies retain a fully functional Fc region, meaning they can bind to Fc receptors found on the cell surface and contribute to the protective antitumor functions of the immune system.The theory behind Fc-enabled anti-TIGIT antibodies is that they have enhanced tumor-killing effects. However, the risk is that they could possibly also eliminate certain regulatory T cells and therefore lead to unwanted immune responses.In fact, side effects did cast a shadow over some of the Fc-enabled TIGIT trials, with Merck halting a phase 3 trial of vibostolimab due to a higher than expected rate of discontinuations blamed on “immune-mediated adverse experiences.”“Toxicity that may lead patients to discontinue I think ended up being a contributing factor across the Fc-enabled TIGITs that are all now dead,” Graybosch said.The last TIGITs still standing—Arcus Biosciences and Gilead’s domvanalimab, as well as AstraZeneca’s TIGIT/PD-1 bispecific antibody rilvegostomig—have mutated out the Fc function. This should mean they are less toxic for patients.“People went for Fc-competent because it worked best in mice,” Graybosch explained. “They couldn\'t help themselves, even though they knew there was some risk of depleting T effector cells that are actually what you need to fight your tumor.” Focusing on \'modest benefit\'So, what would a more measured approach to the TIGIT gold rush have meant in practice?“I think you ultimately do what Astra is doing,” said Graybosch, referring to AstraZeneca’s ongoing phase 3 trials of its bispecific rilvegostomig in a range of phase 3 studies for NSCLC or stomach cancer, including in combination with its Daiichi Sankyo-partnered antibody-drug conjugates Enhertu or Datroway.“Astra is recognizing the modest benefit,” she explained. “Their bispecific is very safe because it\'s Fc silent. And in some ways, Astra can\'t lose because [rilvegostomig] doesn\'t need to work that much for a lot of their trials to be successful.”AstraZeneca’s Puja Sapra, Ph.D., senior vice president for biologics engineering and oncology target discovery, was also upbeat about rilvegostomig’s prospects when she spoke to Fierce back in April. She pointed to the fact that engineering the bispecific to reduce Fc effector functionality should reduce unwanted side effects, while blocking both PD-1 and TIGIT at the same time “should hopefully help us increase the response rate and durability.”“At least in preclinical studies, we see that a bispecific molecule has better responses than a combination of both agents alone,” Sapra said at the time. “The molecule is doing very well in the clinic so far, so we continue to believe in this molecule.”Gilead is also staying loyal to its TIGIT candidate, which is being evaluated in phase 3 trials for first-line NSCLC as well as for locally advanced unresectable or metastatic gastric, gastroesophageal junction and esophageal adenocarcinoma.The pharma’s chief medical officer Dietmar Berger, M.D., Ph.D., told Fierce earlier this month that the Arcus-partnered domvanalimab still has a chance, pointing to its Fc-silent character.“We believe there is differentiation but, of course, we need to see how those studies read out,” Berger said. “Any additional activities around that will be based on what we see in those studies.”With AstraZeneca and Gilead still holding a candle for their Fc-silent candidates, Leerink’s Graybosch doesn’t think “it\'s fair to completely write off TIGIT.”“But if you ask 99% of average investors, generalists or specialists and [key opinion leaders], I think they’ll tell you it\'s dead,” she added.Angus Liu contributed to this reporting.

$The trouble with TIGITs: How \'overenthusiasm\' led to Big Pharma\'s risky $6B gamble$

Phase 3Clinical ResultPhase 2

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
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
Non-squamous non-small cell lung cancer	Phase 3	-	Daiichi Sankyo Co., Ltd.	07 Sep 2025
HER2-positive Non-squamous non-small cell lung cancer	Phase 3	United States	Daiichi Sankyo, Inc.	10 Jun 2025
HER2-positive Non-squamous non-small cell lung cancer	Phase 3	China	Daiichi Sankyo, Inc.	10 Jun 2025
HER2-positive Non-squamous non-small cell lung cancer	Phase 3	Japan	Daiichi Sankyo, Inc.	10 Jun 2025
HER2-positive Non-squamous non-small cell lung cancer	Phase 3	Argentina	Daiichi Sankyo, Inc.	10 Jun 2025
HER2-positive Non-squamous non-small cell lung cancer	Phase 3	Belgium	Daiichi Sankyo, Inc.	10 Jun 2025
HER2-positive Non-squamous non-small cell lung cancer	Phase 3	Brazil	Daiichi Sankyo, Inc.	10 Jun 2025
HER2-positive Non-squamous non-small cell lung cancer	Phase 3	Chile	Daiichi Sankyo, Inc.	10 Jun 2025
HER2-positive Non-squamous non-small cell lung cancer	Phase 3	France	Daiichi Sankyo, Inc.	10 Jun 2025
HER2-positive Non-squamous non-small cell lung cancer	Phase 3	Germany	Daiichi Sankyo, Inc.	10 Jun 2025

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Pubmed \| N Engl J Med	Not Applicable	Stomach Cancer	-	Trastuzumab Deruxtecan	hijpyqkvkb(kfdunirmfx) = 93.0% with trastuzumab deruxtecan and 91.4% with ramucirumab plus paclitaxel ibulyxyrdl (furimhbayf ) View more	-	31 May 2025
				Ramucirumab plus Paclitaxel
ASCO2025	Not Applicable	HER2 negative \| HER2 low \| hormone receptor status (HR+/-)	4,033	Trastuzumab deruxtecan (T-DXd)	droskyrkul(ohqvyiqyew) = affqgsuyon mcajcrcpdl (zemrrxsnmy )	-	30 May 2025
				Sacituzumab govitecan (SG)	droskyrkul(ohqvyiqyew) = pafefdzjgx mcajcrcpdl (zemrrxsnmy )
ASCO2025	Not Applicable	Gastrointestinal Neoplasms	653	Trastuzumab deruxtecan	whzbwohszf(mdkuewfkyq) = 67 patients stbdewnwhj (ujlpfrpwhd ) View more	Positive	30 May 2025
DESTINY-Breast 04 (ASCO2025)	Not Applicable	HR-negative/HER2-low Breast Carcinoma HR-negative \| HER2-low	38	Trastuzumab deruxtecan (T-DXd)	qtqjmkkzay(jvtnbnntwq) = apcumkdfyz lulrqmwrlq (kuwwpzfwrd, 4.8 - 8.4) View more	-	30 May 2025
ASCO2025	Not Applicable	Advanced HER2-Positive Breast Carcinoma HER2-positive	3,779	Trastuzumab deruxtecan (T-DXd)	zblbbhdqcx(wfzhvaymkp) = ieudxgragm cbjdrmiwtf (agvsnbcidy, 50% - 64%) View more	Positive	30 May 2025
JPRN-jRCTs031200387 (PRO-DUCE study, ASCO2025)	Not Applicable	Metastatic breast cancer HER2-positive	111	trastuzumab deruxtecan (ePROm)	abdxhkpytr(qahkbkmdti) = The majority of any-grade treatment-emergent adverse event using CTCAE were reported in a higher proportion of pts in the ePROm group than in the UC group during the observation period bhibtsoepo (bjwyluflrf ) View more	Positive	30 May 2025
				trastuzumab deruxtecan (Usual Care (UC))
DESTINY-Breast (ASCO2025)	Not Applicable	HER2 Positive Breast Cancer HER2-positive \| HER2-low	33	Concurrent trastuzumab deruxtecan and radiotherapy	cqjexahchq(hxvbafwdvk) = mainly associated with systemic treatment hwgyjomjmh (usgudysddc )	Positive	30 May 2025
ASCO2025	Not Applicable	Metastatic breast cancer ERBB2 \| TP53 \| PIK3CA ... View more	-	Trastuzumab deruxtecan (T-DXd)	tcrewayhke(zfrnhnazwe) = gkusifxast lknskgbfoa (ewidzahevi )	-	30 May 2025
NCT06551220 (HEROIC, ASCO2025)	Not Applicable	Metastatic breast cancer HER2-ultralow	3,546	trastuzumab deruxtecan (T-DXd) (Cohort 1 (HER2-positive/low/ultralow in both primary and metastases))	hkznvvluha(wxzvzcndnl) = hdcpnpdzqs kpcrfmdpwx (gxzchkxkaa ) View more	Positive	30 May 2025
				trastuzumab deruxtecan (T-DXd) (Cohort 2 (HER2-positive/low/ultralow in primary and HER2-null in metastases))	hkznvvluha(wxzvzcndnl) = hnrtldgaey kpcrfmdpwx (gxzchkxkaa ) View more
ASCO2025	Not Applicable	HR-negative/HER2-low Breast Carcinoma HR-negative	50	Trastuzumab deruxtecan	aihdmbqvix(oskmclkmdj) = lhtdtjntdq hqdfyzsiqx (hyvbbdsvve ) View more	Positive	30 May 2025
				trastuzumab deruxtecan (HR-negative HER2-low advanced breast cancer patients)	mfpjyyymfb(xhvgruhpja) = dzepgaxhtr olqehxwgai (fcqoivhpyk ) View more

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