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- \nFirst Breakthrough Therapy Designation for Daiichi Sankyo and Merck\u2019s raludotatug deruxtecan based on phase 1 trial and REJOICE-Ovarian01 phase 2\/3 trial<\/p>\n<\/li>\n
- \nSecond Breakthrough Therapy Designation since the start of the Daiichi Sankyo and Merck collaboration<\/p>\n<\/li>\n
- \nFifteenth Breakthrough Therapy Designation granted by FDA across the oncology portfolio of Daiichi Sankyo<\/p>\n<\/li>\n<\/ul>\n
BASKING RIDGE, N.J. & RAHWAY, N.J.–(BUSINESS WIRE<\/a>)–
\nRaludotatug deruxtecan (R-DXd) has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancers expressing CDH6 who have received prior treatment with bevacizumab.<\/p>\n\nRaludotatug deruxtecan is a specifically engineered, potential first-in-class CDH6 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and Merck (NYSE: MRK), known as MSD outside of the United States and Canada.<\/p>\n
\nThe FDA BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The medicine is required to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over currently available medicines.<\/p>\n
\nThe FDA granted this BTD based on data from a phase 1 trial<\/a> and the ongoing REJOICE-Ovarian01<\/a> phase 2\/3 trial. A subgroup analysis of the phase 1 trial was presented<\/a> at the 2023 European Society for Medical Oncology meeting (#ESMO23). Subsequent subgroup analyses of the phase 1 trial were presented at the 2024 Society for Gynecologic Oncology Annual Meeting on Women\u2019s Cancer and the 2025 European Society for Medical Oncology Gynaecological Cancers Congress. This is the first BTD for raludotatug deruxtecan and represents the second BTD since the start of the Daiichi Sankyo and Merck collaboration.<\/p>\n
\n\u201cPatients have limited treatment options once ovarian cancer becomes resistant to platinum-based chemotherapy, highlighting the urgent need for new medicines that can improve patient outcomes,\u201d said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. \u201cThe receipt of Breakthrough Therapy Designation represents an important step forward in our efforts to advance raludotatug deruxtecan as a novel medicine for patients with CDH6 expressing platinum-resistant ovarian, primary peritoneal or fallopian tube cancers previously treated with bevacizumab.\u201d<\/p>\n
\n\u201cThe FDA’s Breakthrough Designation is a reflection of our commitment to advancing research for patients impacted by women\u2019s cancers,\u201d said Eliav Barr, MD, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories. \u201cRaludotatug deruxtecan has the potential to one day become an important option for the treatment of patients with CDH6 expressing platinum-resistant ovarian, primary peritoneal or fallopian tube cancers previously treated with bevacizumab, and we are excited to share data from REJOICE-Ovarian01 with the scientific community at an upcoming medical meeting and to continue working closely with the FDA.\u201d<\/p>\n
About the Phase 1 Trial
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<\/b>The two-part, multicenter, open-label, first-in-human phase 1 trial<\/a> is evaluating the safety and efficacy of investigational raludotatug deruxtecan in adult patients with advanced ovarian cancer previously treated with platinum-based chemotherapy and a taxane. Patients with renal cell carcinoma resistant or refractory to standard of care therapy were originally included, but that component of the study was discontinued.<\/p>\n\nThe primary objective of the first part of the study (dose escalation) was to assess the safety and tolerability of increasing doses of raludotatug deruxtecan to determine the maximum tolerated dose (MTD) and\/or recommended dose for expansion (RDE). The primary objective of the second part of the study (dose expansion) is to further evaluate the safety and efficacy of raludotatug deruxtecan in patients with advanced ovarian cancer and in patients with advanced renal cell carcinoma.<\/p>\n
\nThe study will evaluate safety endpoints, including dose-limiting toxicities and adverse events and efficacy endpoints, including objective response rate (ORR), duration of response (DoR), disease control rate (DCR), clinical benefit rate, time to response and progression free survival (PFS). Pharmacokinetic and exploratory biomarker endpoints also will be assessed.<\/p>\n
\nThe phase 1 trial enrolled 179 patients in Asia and North America. For more information, please visit ClinicalTrials.gov<\/a>.<\/p>\n
About REJOICE-Ovarian01
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<\/b>REJOICE-Ovarian01<\/a> is a global, multicenter, randomized, open-label phase 2\/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan in patients with platinum-resistant, high-grade ovarian, primary peritoneal or fallopian tube cancer, with disease progression following at least one but no more than three prior lines of systemic therapy, including prior treatment with mirvetuximab soravtansine for those with documented high-folate receptor alpha expression. Maintenance therapy (e.g., bevacizumab, poly ADP-ribose polymerase [PARP] inhibitors) is considered part of the preceding line of therapy.<\/p>\n\nThe phase 2 part of REJOICE-Ovarian01 is assessing the safety and tolerability of three doses of raludotatug deruxtecan (4.8 mg\/kg, 5.6 mg\/kg, or 6.4 mg\/kg) to identify the recommended dose for the phase 3 part of the trial. The primary endpoint of the phase 2 part of the trial is ORR as assessed by blinded independent central review (BICR). Secondary endpoints include ORR as assessed by investigator, DoR, PFS and DCR \u2013 all assessed by both BICR and investigator \u2013 and overall survival (OS).<\/p>\n
\nThe phase 3 part of REJOICE-Ovarian01 is assessing the efficacy and safety of raludotatug deruxtecan at the selected dose (5.6 mg\/kg) compared to investigator\u2019s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, gemcitabine or topotecan). The dual primary endpoints of the phase 3 part of the trial are ORR and PFS as assessed by BICR. Secondary endpoints include PFS and ORR as assessed by investigator, DoR and DCR as assessed by both BICR and investigator, and OS. Pharmacokinetic and biomarker endpoints also will be assessed in both parts of the trial.<\/p>\n
\nREJOICE-Ovarian01 is expected to enroll approximately 710 patients across Asia, Europe, North America, and Oceania. For more information, please visit ClinicalTrials.gov<\/a>.<\/p>\n
About Ovarian Cancer
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<\/b>More than 324,000 women were diagnosed with ovarian cancer worldwide in 2022.1<\/sup> The median overall survival for advanced ovarian cancer following recurrence can be as little as two years, with a five-year survival rate of 31.8% for those with distant stage disease.2,3<\/sup><\/p>\n\nThe introduction of targeted therapies has expanded treatment options and improved survival outcomes for some patients with ovarian cancer, but additional options are needed for patients with tumors that progress on available medicines.4<\/sup> Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens.5 <\/sup>For patients who develop platinum-resistant ovarian cancer, defined as disease progression less than six months after completion of last platinum-based chemotherapy, prognosis is particularly poor and treatment options are limited.6,7<\/sup><\/p>\n
About CDH6
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<\/b>CDH6 (human cadherin-6) is a cadherin family protein overexpressed in several cancers, including ovarian tumors.8<\/sup> An estimated 65% of patients with ovarian cancer have tumors that express CDH6.9<\/sup> In addition, CDH6 expression is observed more frequently in high-grade serous carcinomas.9<\/sup> There is currently no CDH6 directed medicine approved for treatment of any cancer.<\/p>\nAbout Raludotatug Deruxtecan
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<\/b>Raludotatug deruxtecan is an investigational, potential first-in-class CDH6 directed ADC. Designed using Daiichi Sankyo\u2019s proprietary DXd ADC Technology, raludotatug deruxtecan is comprised of a humanized anti-CDH6 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.<\/p>\nAbout the Daiichi Sankyo and Merck Collaboration
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<\/b>Daiichi Sankyo and Merck (known as MSD outside of the United States and Canada) entered into a global collaboration in October 2023<\/a> to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply. In August 2024<\/a>, the global co-development and co-commercialization agreement was expanded to include gocatamig (MK-6070\/DS3280), which the companies will jointly develop and commercialize worldwide, except in Japan where Merck & Co., Inc., Rahway, N.J., USA will maintain exclusive rights. Merck & Co., Inc., Rahway, N.J., USA will be solely responsible for manufacturing and supply for gocatamig.<\/p>\nAbout the ADC Portfolio of Daiichi Sankyo
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<\/b>The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo.<\/p>\n\nThe ADC platform furthest in clinical development is Daiichi Sankyo\u2019s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU\u00ae<\/sup>, a HER2 directed ADC, and DATROWAY\u00ae<\/sup>, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc., Rahway, N.J., USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo.<\/p>\n
\nThe second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.<\/p>\n
\nIfinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.<\/p>\n
About Daiichi Sankyo
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<\/b>Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical needs. For more information, please visit www.daiichisankyo.com<\/a>.<\/p>\nMerck\u2019s Focus on Cancer
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<\/b>Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit www.merck.com\/research\/oncology\/<\/a>.<\/p>\nAbout Merck
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<\/strong>At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world \u2013 and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com<\/a> and connect with us on X (formerly Twitter)<\/a>, Facebook<\/a>, Instagram<\/a>, YouTube<\/a> and LinkedIn<\/a>.<\/p>\nForward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA
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<\/b>This news release of Merck & Co., Inc., Rahway, N.J., USA (the \u201ccompany\u201d) includes \u201cforward-looking statements\u201d within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company\u2019s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.<\/p>\n\nRisks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company\u2019s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company\u2019s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and\/or regulatory actions.<\/p>\n
\nThe company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company\u2019s Annual Report on Form 10-K for the year ended December 31, 2024, and the company\u2019s other filings with the Securities and Exchange Commission (SEC) available at the SEC\u2019s Internet site (www.sec.gov<\/a>).<\/p>\n
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