A Phase 3, Open-Label, Multicenter, Randomized Study of Raludotatug Deruxtecan (MK-5909, R-DXd) With or Without Bevacizumab Versus Standard-of-Care Platinum-Based Doublet Chemotherapy With or Without Bevacizumab in Participants With Advanced Platinum-Sensitive High-Grade Serous or High-Grade Endometrioid Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Have Progressed During First-Line PARPi Maintenance (ENGOT-ov107 / GOG-3142 / REJOICE-Ovarian05)

Researchers are looking for new ways to treat advanced, high-grade ovarian cancer (OC). Advanced means the cancer has spread to other parts of the body (metastatic) and may not be removed with surgery. High-grade means the cancer cells grow and spread quickly. This trial includes types of OC that started in cells that cover the ovaries, in the lining of the belly, or in the fallopian tubes.
The usual treatment for high-grade OC may include one or both of these:
* Chemotherapy, which is a treatment that uses medicine to destroy cancer cells or stop them from growing.
* Bevacizumab, which is a targeted therapy that works to control how specific types of cancer cells grow and spread and targets tumor blood vessels.
Researchers want to learn about the trial medicine, raludotatug deruxtecan (also called R-DXd or MK-5909), when given with and without bevacizumab and how participants respond to it. R-DXd is an antibody drug conjugate (ADC). An ADC is a type of medicine that attaches to a specific target on cancer cells and delivers treatment to destroy those cells.
The goals of this trial are to learn if participants who receive R-DXd, with or without bevacizumab, live longer overall and without their cancer growing or spreading compared to those who receive usual treatment.

Start Date05 Oct 2026

Sponsor / Collaborator

Merck Sharp & Dohme LLC

[+1]

NCT07791732

/ Not yet recruitingPhase 3

A Phase 3, Multicenter, Randomized, Open-Label Trial of Raludotatug Deruxtecan With or Without Bevacizumab as Maintenance Therapy Versus Standard of Care in Participants With First Recurrence Platinum-Sensitive, High-Grade Serous or Endometrioid Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (REJOICE-Ovarian03)

The primary purpose of the study is to evaluate the efficacy of R-DXd with or without bevacizumab as maintenance therapy compared with standard of care (SOC) in participants with platinum-sensitive ovarian cancer (PSOC) as measured by progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR).

Start Date01 Oct 2026

Sponsor / Collaborator

Daiichi Sankyo Co., Ltd.

[+1]

NCT07776691

/ RecruitingPhase 3

A Phase 3, Randomized, Open-label Study of Raludotatug Deruxtecan (MK-5909, R-DXd) Maintenance Treatment With or Without Bevacizumab Versus Standard of Care in Participants With Newly-Diagnosed Advanced Non-HRD-Positive Ovarian Cancer Following First-line Platinum-based Chemotherapy (ENGOT-ov102/MITO/GOG-3141/ REJOICE-Ovarian 04)

Researchers are looking for new ways to treat ovarian cancer (OC). Current treatment for OC may start with surgery to remove as much of the cancer as possible. After surgery, people may receive chemotherapy. After chemotherapy, standard care options may include:
Maintenance treatment, which is used after another therapy to keep the cancer from growing, spreading, or coming back. Bevacizumab is a targeted therapy used as standard maintenance treatment. Targeted therapy works to control how specific types of cancer cells grow and spread.
Observation, which is watching to see if cancer grows or worsens. The study medicine, raludotatug deruxtecan- R-DXd, is a targeted therapy. The goal of this study is to learn if people who receive R-DXd maintenance treatment with or without bevacizumab live longer without the cancer getting worse than people who receive standard care.

Start Date18 Sep 2026

Sponsor / Collaborator

Merck Sharp & Dohme LLC

[+1]

100 Clinical Results associated with Raludotatug deruxtecan

100 Translational Medicine associated with Raludotatug deruxtecan

100 Patents (Medical) associated with Raludotatug deruxtecan

Literatures (Medical) associated with Raludotatug deruxtecan

14 Nov 2024·JOURNAL OF MEDICINAL CHEMISTRY

Evaluation of Double Self-Immolative Linker-Based Antibody–Drug Conjugate FDA022-BB05 with Enhanced Therapeutic Potential

Article

Author: Yin, Sicheng ; Liu, Shuangxi ; Zhang, Yifan ; Yang, Tong ; Zhang, Wenbo ; Shen, Keyu ; Xie, Qian ; Zhu, Shulei ; Gao, Bei ; Wu, Yinghan ; Song, Ruiwen ; Cao, Xuemei ; Qiu, Xuefei ; Cheng, Zhiyang ; Wang, Baoxia ; Zhao, Teng ; Xu, Jun ; Wu, Jingsong ; Li, Weinan ; Guo, Qingsong ; Wang, Lei ; Lu, Wei

Typical antibody-drug conjugates (ADCs) with valine-alanine linkage, often conjugated with the amino group in payloads, face challenges when interacting with hydroxyl group-containing payloads. Herein, we introduced a transformative Val-Ala-based double self-immolative linker-payload platform, reshaping ADCs by optimizing hydroxyl group-containing payload integration. Utilizing this platform, FDA022-BB05 was successfully conjugated with the hydroxyl group-containing payload DXd using trastuzumab (FDA022) as the monoclonal antibody (mAb). FDA022-BB05 demonstrated enhanced stability, effective cathepsin B sensitivity, reduced cell proliferation, increased bystander killing, and targeted delivery. Notably, acute toxicity evaluations in diverse preclinical models indicated favorable safety profiles and tolerability, with a broad therapeutic index in HER2-positive and -negative xenografts. Overall, these compelling findings support the promising therapeutic potential of FDA022-BB05, emphasizing the significance of diverse linker-payload platform strategies. This ADC is a valuable addition to targeted cancer therapy development, currently advancing through phase I clinical trials.

01 Oct 2024·MOLECULAR CANCER THERAPEUTICS

FZ-AD005, a Novel DLL3-Targeted Antibody–Drug Conjugate with Topoisomerase I Inhibitor, Shows Potent Antitumor Activity in Preclinical Models

Article

Author: Wu, Jinsong ; Lu, Wei ; Shen, Jiafei ; Zhao, Teng ; Gao, Bei ; Yang, Tong ; Song, Ruiwen ; Guo, Qingsong ; Xie, Qian ; Lou, Sensen ; Li, Weinan ; Zhang, Yifan ; Zhu, Shulei ; Wang, Lei

Abstract:

Delta-like ligand 3 (DLL3) is overexpressed in small cell lung cancer (SCLC) and has been considered an attractive target for SCLC therapy. Rovalpituzumab tesirine was the first DLL3-targeted antibody–drug conjugate (ADC) to enter clinical studies. However, serious adverse events limited progress in the treatment of SCLC with rovalpituzumab tesirine. In this study, we developed a novel DLL3-targeted ADC, FZ-AD005, by using DXd with potent cytotoxicity and a relatively better safety profile to maximize the therapeutic index. FZ-AD005 was generated by a novel anti-DLL3 antibody, FZ-A038, and a valine–alanine (Val–Ala) dipeptide linker to conjugate DXd. Moreover, Fc-silencing technology was introduced in FZ-AD005 to avoid off-target toxicity mediated by FcγRs and showed negligible Fc-mediated effector functions in vitro. In preclinical evaluation, FZ-AD005 exhibited DLL3-specific binding and demonstrated efficient internalization, bystander killing, and excellent in vivo antitumor activities in cell line–derived xenograft and patient-derived xenograft models. FZ-AD005 was stable in circulation with acceptable pharmacokinetic profiles in cynomolgus monkeys. FZ-AD005 was well tolerated in rats and monkeys. The safety profile of FZ-AD005 was favorable, and the highest nonseverely toxic dose was 30 mg/kg in cynomolgus monkeys. In conclusion, FZ-AD005 has the potential to be a superior DLL3-targeted ADC with a wide therapeutic window and is expected to provide clinical benefits for the treatment of patients with SCLC.

01 May 2024·Analytica chimica acta

Quantifying payloads of antibody‒drug conjugates using a postcolumn infused-internal standard strategy with LC‒MS

Article

Author: Yen-Shen Lu ; Wen-Chi Chang ; Hsiao-Wei Liao ; Ching-Hua Kuo ; Ching-Hung Lin ; Chih-Ning Cheng ; I-Chun Chen

BACKGROUND:

Antibody‒drug conjugates (ADCs) are innovative biopharmaceutics consisting of a monoclonal antibody, linkers, and cytotoxic payloads. Monitoring circulating payload concentrations has the potential to identify ADC toxicity; however, accurate quantification faces challenges, including low plasma concentrations, severe matrix effects, and the absence of stable isotope-labeled internal standards (SIL-IS) for payloads and their derivatives. Previous studies used structural analogs as internal standards, but different retention times between structural analogs and target analytes may hinder effective matrix correction. Therefore, a more flexible approach is required for precise payload quantification.

RESULTS:

We developed an LC‒MS/MS method incorporating a postcolumn-infused internal standard (PCI-IS) strategy for quantifying payloads and their derivatives of trastuzumab emtansine, trastuzumab deruxtecan, and sacituzumab govitecan, including DM1, MCC-DM1, DXd, SN-38, and SN-38G. Structural analogs (maytansine, Lys-MCC-DM1, and exatecan) were selected as PCI-IS candidates, and their accuracy performance was evaluated based on the percentage of samples within 80%-120% quantification accuracy. Compared to the approach without PCI-IS correction, exatecan enhanced the accuracy performance from 30-40%-100% for SN-38 and DXd, while maytansine and Lys-MCC-DM1 showed comparable accuracy for DM1 and MCC-DM1. This validated PCI-IS analytical method showed superior normalization of matrix effect in all analytes compared to the conventional internal standard approach. The clinical application of this approach showed pronounced differences in DXd and SN-38 concentrations before and after PCI-IS correction. Moreover, only DXd concentrations after PCI-IS correction were significantly higher in patients with thrombocytopenia (p = 0.037).

SIGNIFICANCE:

This approach effectively addressed the issue of unavailability of SIL-IS for novel ADC payloads and provided more accurate quantification, potentially yielding more robust statistical outcomes for understanding the exposure-toxicity relationship in ADCs. It is anticipated that this PCI-IS strategy may be extrapolated to quantify payloads and derivatives in diverse ADCs, thereby providing invaluable insights into drug toxicity and fortifying patient safety in ADC usage.

179

News (Medical) associated with Raludotatug deruxtecan

02 Oct 2026

·www.businesswire.com

Daiichi Sankyo and AstraZeneca Enter into Clinical Trial Collaboration with Summit Therapeutics to Evaluate Datroway ® in Combination with Ivonescimab Across Multiple Tumor Types

TOKYO--(BUSINESS WIRE)--Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/NYSE: AZN) have entered into a clinical trial collaboration agreement with Summit Therapeutics Inc. (Nasdaq: SMMT) to evaluate Datroway® (datopotamab deruxtecan) in combination with ivonescimab across multiple tumor types including lung and breast cancers. The companies intend to begin with a phase 3 trial in first-line triple negative breast cancer (TNBC). Datroway is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca. “At Daiichi Sankyo, we are focused on maximizing the potential of our DXd antibody drug conjugate portfolio through innovative combinations and strategic collaborations that support the continued advancement of our pipeline,” said John Tsai, MD, Global Head, R&D, Daiichi Sankyo. “We are encouraged by the opportunity to explore ivonescimab in combination with Datroway to potentially deliver clinically meaningful benefit to patients.” “Central to our strategy to transform cancer outcomes is harnessing the power of immunotherapy and antibody drug conjugate combinations to drive deeper, more durable responses,” said Susan Galbraith, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “We believe the combination of Datroway and ivonescimab has the potential to make a meaningful difference in multiple tumor types including lung and breast cancers.” “We believe this collaboration with Daiichi Sankyo and AstraZeneca reflects increasing conviction in ivonescimab’s potential as a foundational next-generation immunotherapy and advances our ambition for ivonescimab to become the global PD-1/VEGF partner of choice for novel combinations,” said Maky Zanganeh, President and Co-Chief Executive Officer, Summit Therapeutics. “Beginning with a phase 3 study in first-line triple negative breast cancer, this collaboration represents an important expansion of Summit’s global development program into breast cancer and a path for additional solid tumor settings.” Under the terms of the agreement, each company will contribute their respective compound for the planned combination trials, which will be sponsored by AstraZeneca or Daiichi Sankyo. AstraZeneca, Daiichi Sankyo and Summit will each contribute to trial costs, and each company will retain development and commercial rights to their respective medicines. Ivonescimab is a novel, potential first-in-class bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. About Datroway Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC. Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, Datroway is one of seven DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datroway 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. Datroway (6 mg/kg) is approved in more than 30 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy based on the results from the TROPION-Breast02 trial. Datroway (6 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 trial. Datroway (6 mg/kg) is approved in Brazil, Russia, Singapore and the U.S. for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy based on the results from TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in a confirmatory trial. About the Datroway Clinical Development Program A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of Datroway across multiple cancers, including non-small cell lung cancer (NSCLC), TNBC and urothelial cancer. The program includes eight phase 3 trials in lung cancer, five phase 3 trials in breast cancer and one phase 3 and one phase 2/3 trial in urothelial cancer evaluating Datroway as a monotherapy and in combination with other cancer 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 Datroway 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 Datroway. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of nine ADCs in clinical development crafted from ADC technology discovered in-house by Daiichi Sankyo. The DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in clinical development where each ADC is comprised of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADCs include Enhertu and Datroway, which are being jointly developed and commercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939 and DS3790 are being developed by Daiichi Sankyo. Additional ADCs being developed by Daiichi Sankyo include DS3610, which consists of an antibody attached to a novel payload that acts as an agonist of STING, and DS1025, which consists of a CD25 directed antibody attached to an immuno-oncology optimized cytotoxic payload. Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610, DS3790 and DS1025 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 (TSE: 4568) is a global healthcare company committed to becoming a trusted healthcare innovator, transforming the lives of people through its strength in science and technology. The company discovers and develops new standards of care to address diverse medical needs to fulfill its purpose of contributing to the enrichment of quality of life around the world. With a strategic focus on oncology, Daiichi Sankyo is advancing an industry-leading antibody drug conjugate portfolio along with identifying new breakthrough generating technologies to deliver practice-changing medicines to patients, healthcare professionals and society. For more information, please visit www.daiichisankyo.com.

ImmunotherapyLicense out/inPhase 3ADCDrug Approval

02 Oct 2026

·www.biospace.com

Daiichi Sankyo and AstraZeneca Enter into Clinical Trial Collaboration with Summit Therapeutics to Evaluate Datroway® in Combination with Ivonescimab Across Multiple Tumor Types

TOKYO--(BUSINESS WIRE)--Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/NYSE: AZN) have entered into a clinical trial collaboration agreement with Summit Therapeutics Inc. (Nasdaq: SMMT) to evaluate Datroway ® (datopotamab deruxtecan) in combination with ivonescimab across multiple tumor types including lung and breast cancers. The companies intend to begin with a phase 3 trial in first-line triple negative breast cancer (TNBC). Datroway is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca. “At Daiichi Sankyo, we are focused on maximizing the potential of our DXd antibody drug conjugate portfolio through innovative combinations and strategic collaborations that support the continued advancement of our pipeline,” said John Tsai, MD, Global Head, R&D, Daiichi Sankyo. “We are encouraged by the opportunity to explore ivonescimab in combination with Datroway to potentially deliver clinically meaningful benefit to patients.” “Central to our strategy to transform cancer outcomes is harnessing the power of immunotherapy and antibody drug conjugate combinations to drive deeper, more durable responses,” said Susan Galbraith, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “We believe the combination of Datroway and ivonescimab has the potential to make a meaningful difference in multiple tumor types including lung and breast cancers.” “We believe this collaboration with Daiichi Sankyo and AstraZeneca reflects increasing conviction in ivonescimab’s potential as a foundational next-generation immunotherapy and advances our ambition for ivonescimab to become the global PD-1/VEGF partner of choice for novel combinations,” said Maky Zanganeh, President and Co-Chief Executive Officer, Summit Therapeutics. “Beginning with a phase 3 study in first-line triple negative breast cancer, this collaboration represents an important expansion of Summit’s global development program into breast cancer and a path for additional solid tumor settings.” Under the terms of the agreement, each company will contribute their respective compound for the planned combination trials, which will be sponsored by AstraZeneca or Daiichi Sankyo. AstraZeneca, Daiichi Sankyo and Summit will each contribute to trial costs, and each company will retain development and commercial rights to their respective medicines. Ivonescimab is a novel, potential first-in-class bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. About Datroway Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC. Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, Datroway is one of seven DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datroway 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. Datroway (6 mg/kg) is approved in more than 30 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy based on the results from the TROPION-Breast02 trial. Datroway (6 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 trial. Datroway (6 mg/kg) is approved in Brazil, Russia, Singapore and the U.S. for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy based on the results from TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in a confirmatory trial. About the Datroway Clinical Development Program A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of Datroway across multiple cancers, including non-small cell lung cancer (NSCLC), TNBC and urothelial cancer. The program includes eight phase 3 trials in lung cancer, five phase 3 trials in breast cancer and one phase 3 and one phase 2/3 trial in urothelial cancer evaluating Datroway as a monotherapy and in combination with other cancer 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 Datroway 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 Datroway. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of nine ADCs in clinical development crafted from ADC technology discovered in-house by Daiichi Sankyo. The DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in clinical development where each ADC is comprised of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADCs include Enhertu and Datroway, which are being jointly developed and commercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939 and DS3790 are being developed by Daiichi Sankyo. Additional ADCs being developed by Daiichi Sankyo include DS3610, which consists of an antibody attached to a novel payload that acts as an agonist of STING, and DS1025, which consists of a CD25 directed antibody attached to an immuno-oncology optimized cytotoxic payload. Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610, DS3790 and DS1025 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 (TSE: 4568) is a global healthcare company committed to becoming a trusted healthcare innovator, transforming the lives of people through its strength in science and technology. The company discovers and develops new standards of care to address diverse medical needs to fulfill its purpose of contributing to the enrichment of quality of life around the world. With a strategic focus on oncology, Daiichi Sankyo is advancing an industry-leading antibody drug conjugate portfolio along with identifying new breakthrough generating technologies to deliver practice-changing medicines to patients, healthcare professionals and society. For more information, please visit . Contacts MEDIA CONTACTS: G lobal: Jennifer Brennan jennifer.brennan@daiichisankyo.com + 1 908 900 3183 (mobile) Japan: DS-PR_jp@daiichisankyo.com INVESTOR RELATIONS CONTACT: DaiichiSankyoIR_jp@daiichisankyo.com

ImmunotherapyLicense out/inPhase 3ADCDrug Approval

28 Sep 2026

·www.fiercebiotech.com

Merck and Daiichi pull lung cancer filing after FDA pushback

Daiichi Sankyo and Merck & Co. have withdrawn an antibody-drug conjugate (ADC) filing after the FDA said they lacked the data for accelerated approval in a lung cancer population. The partners filed for accelerated approval of their B7-H3-directed ADC, ifinatamab deruxtecan (I-DXd), based on data from the phase 2 IDeate-Lung01 study. The clinical trial enrolled 187 participants with extensive-stage small cell lung cancer (ES-SCLC) who were previously treated with at least one prior line of platinum-based chemotherapy. Researchers called the phase 2 efficacy “promising.” However, the FDA told Daiichi and Merck that the data supporting the application falls short of the level needed to meet the requirements for accelerated approval. In response, the partners voluntarily pulled the filing for accelerated approval in ES-SCLC that progressed on or after platinum-based chemotherapy. Merck is “disappointed that the current dataset are not supportive of an approval at this time,” Marjorie Green, M.D., head of oncology, global clinical development at Merck Research Laboratories, said in a statement. But with enrollment in the phase 3 IDeate-Lung02 trial nearing completion, the partners may return to the FDA with an expanded dataset in the future. The withdrawal has potential implications for Amgen and GSK. Amgen sells a DLL3xCD3 T-cell engager, Imdelltra, for ES-SCLC patients who progress on platinum-based chemotherapy. GSK is developing a rival B7-H3-directed ADC, risvutatug rezetecan, which recently impressed in a phase 3 trial in China. Phase 3 trials in castration-resistant prostate cancer and esophageal squamous cell carcinoma give I-DXd other paths to market. Even so, the withdrawal of the ES-SCLC filing represents another blow to a deal that has disappointed to date. Merck paid Daiichi $4 billion upfront in 2023 to partner on three ADCs. The FDA rejected a request for approval of one of the ADCs, the HER3-directed asset patritumab deruxtecan (HER3-DXd), in 2024 on manufacturing grounds. The next year, Daiichi and Merck voluntarily withdrew a HER3-DXd submission after failing to show improved overall survival. The partners continued to test HER3-DXd, including in an ongoing phase 3 breast cancer trial, but shifted their hopes for near-term sales to I-DXd. The I-DXd withdrawal pushes back the timeline for generating a return on the ADC. Phase 3 trials of I-DXd in ES-SCLC, prostate cancer and esophageal squamous cell carcinoma have primary completion dates in 2028, according to the federal trials database. Raludotatug deruxtecan (R-DXd), a CDH6-directed ADC, is the third asset covered by the deal. A phase 2/3 trial of R-DXd in ovarian cancer has a primary completion date of February 2028 on the trials register.

Phase 3ADCPhase 2Accelerated Approval

100 Deals associated with Raludotatug deruxtecan

External Link

KEGG	Wiki	ATC	Drug Bank
D13069	-	-	-

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Ovarian Serous Tumor	Phase 3	-	Daiichi Sankyo Co., Ltd.	01 Oct 2026
Platinum-Sensitive Fallopian Tube Carcinoma	Phase 3	-	Daiichi Sankyo Co., Ltd.	01 Oct 2026
Platinum-Sensitive Ovarian Carcinoma	Phase 3	-	Daiichi Sankyo Co., Ltd.	01 Oct 2026
Fallopian Tube Carcinoma	Phase 3	United States	Merck Sharp & Dohme LLC	18 Sep 2026
HRD-positive Ovarian Cancer	Phase 3	United States	Merck Sharp & Dohme LLC	18 Sep 2026
HRD-positive Ovarian Cancer	Phase 3	Israel	Merck Sharp & Dohme LLC	18 Sep 2026
Platinum-Resistant Fallopian Tube Carcinoma	Phase 3	United States	Daiichi Sankyo Co., Ltd.	27 Feb 2024
Platinum-Resistant Fallopian Tube Carcinoma	Phase 3	United States	Merck Sharp & Dohme LLC	27 Feb 2024
Platinum-Resistant Fallopian Tube Carcinoma	Phase 3	China	Daiichi Sankyo Co., Ltd.	27 Feb 2024
Platinum-Resistant Fallopian Tube Carcinoma	Phase 3	China	Merck Sharp & Dohme LLC	27 Feb 2024

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06161025 (REJOICE-Ovarian01, ASCO2026)	Phase 3	Platinum-Resistant Ovarian Carcinoma CDH6 expression	600	R-DXd 5.6 mg/kg	cqudzdbelf(jzbanyoihg) = aqblchdper maydwkpdqa (xvnzdlvlau, 42.9 - 57.1) View more	Positive	29 May 2026
NCT04707248 (REJOICE-Ovarian01, ASCO2026)	Phase 1/2	Platinum-Resistant Ovarian Carcinoma CDH6 expression	286	Raludotatug deruxtecan 5.6 mg/kg Q3W	bfulzteiwu(mxzeetnjsx) = Higher R-DXd or DXd payload exposure was associated with an increase in drug-related TEAEs, including Grade ≥3 (G3+) AEs, any-grade ILD, G2+ gastrointestinal AEs (nausea/vomiting), G3+ cytopenias (anemia, neutropenia, thrombocytopenia), and AEs leading to dose reduction. hudclacjun (iuoqrmgtas ) View more	Positive	29 May 2026
NCT04707248 (REJOICE-PanTumor01, ASCO_GU2026)	Phase 2	Urogenital Neoplasms \| Genital Diseases, Female CDH6	40	R-DXd 5.6 mg/kg (Cervical Cancer)	lyhmvxftyy(sfcxehmzru) = fphincuklq fdgemjdsti (befobuznet )	Positive	26 Feb 2026
				R-DXd 5.6 mg/kg (Non-HGSOC)	lyhmvxftyy(sfcxehmzru) = hjokwlslwk fdgemjdsti (befobuznet )
NCT06161025 (REJOICE-Ovarian01, ESMO 12025 \| ESMO 22025) Manual	Phase 2	Platinum-Resistant Fallopian Tube Carcinoma \| Platinum-Resistant Primary Peritoneal Carcinoma \| Platinum-Resistant Ovarian Carcinoma	107	R-DXd (4.8 mg/kg)	forwwjjmmf(gbqfowrhfk) = vuahyojwdi gegdwzgkne (svikakfaog, 27.9 - 61.9) View more	Positive	17 Oct 2025
				R-DXd (5.6 mg/kg)	forwwjjmmf(gbqfowrhfk) = jbndpfvvbn gegdwzgkne (svikakfaog, 32.9 - 67.1) View more
NCT06780085 (KEYMAKER-U01, ESMO2025)	Phase 2	metastatic non-small cell lung cancer	240	R-DXd 5.6 mg/kg Q3W	urmbhlgbco(hksghwrucg) = gwhwtewtxw yykujmwjgm (pgulxjemiz )	Positive	17 Oct 2025
				I-DXd 12 mg/kg Q3W	urmbhlgbco(eouexivkmp) = gyvepjsnkj gxwfcegoby (sarldolojt ) View more
NCT04707248 (ESMO 12023 \| ESMO 22023) Manual	Phase 1	Ovarian Cancer	42	R-DXd at 4.8 mg/kg	xkrdgczrzk(yvhgsakkuh) = yffgglnhdc qvspqvdahx (wcguhnebnq ) View more	Positive	22 Oct 2023
				R-DXd at 6.4 mg/kg	xkrdgczrzk(yvhgsakkuh) = fslamvbnyx qvspqvdahx (wcguhnebnq ) View more
NCT04707248 (Corporate Publications) Manual	Phase 1	Ovarian Cancer	50	Raludotatug deruxtecan	hujbgopeyn(ejqlgxxkhd) = axdtgxguch mbnfhzoutv (aozdklyhmi, 32 - 61) View more	Positive	22 Oct 2023
NCT04707248 (ASCO2022) Manual	Phase 1	Ovarian Cancer \| Advanced Renal Cell Carcinoma	22	DS-6000a	rndggxyrtk(tihogrutku) = ofpyrhfdzd xdvrniirwp (vkgrpfxrib ) View more	Positive	02 Jun 2022

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