Daiichi Sankyo (TSE: 4568) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the first patient has been dosed in the REJOICE-Ovarian01 phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan (R-DXd) in patients with platinum-resistant ovarian cancer. The phase 2 portion of the trial will be conducted to identify the dose of raludotatug deruxtecan to be used in the phase 3 part of the trial, which will evaluate raludotatug deruxtecan versus investigator’s choice of chemotherapy.

Raludotatug deruxtecan is an investigational specifically engineered potential first-in-class CDH6 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed with Merck.

Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens.¹ The median overall survival for advanced ovarian cancer following recurrence is approximately two years, with a five-year survival rate of less than 30%.^2,3 Up to 85% of advanced ovarian tumors have overexpression of CDH6, which is associated with poor prognosis.^4,5

The initiation of REJOICE-Ovarian01 is based on results from an ongoing phase 1 trial of raludotatug deruxtecan presented at the European Society for Medical Oncology Congress 2023 with a subgroup analysis presented at the Society for Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer.

“Raludotatug deruxtecan has shown promising activity in a phase 1 trial of patients with advanced ovarian cancer,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “The REJOICE-Ovarian01 trial, which is our first trial initiation for raludotatug deruxtecan in collaboration with Merck, will evaluate the efficacy of this CDH6 directed DXd antibody drug conjugate versus investigator’s choice of chemotherapy in patients with platinum-resistant ovarian cancer.”

“The prognosis for the majority of patients diagnosed with advanced ovarian cancer is bleak, with a low five-year survival rate, underscoring the critical need for the development of innovative and effective therapies,” said Marjorie Green, MD, Senior Vice President and Head of Late-Stage Oncology, Global Clinical Development, Merck Research Laboratories. “We look forward to working with our colleagues at Daiichi Sankyo to further evaluate the potential of raludotatug deruxtecan to provide a new treatment option for patients with platinum-resistant ovarian cancer.”

About the REJOICE-Ovarian01 Trial

REJOICE-Ovarian01 is a global, multicenter, randomized, open-label phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan (R-DXd) in patients with platinum-resistant, high-grade ovarian cancer, including primary peritoneal or fallopian tube cancer, who received at least one and no more than three prior systemic lines of anticancer therapy, including prior treatment with mirvetuximab soravtansine for those with documented high-folate receptor alpha expression.

The phase 2 part of REJOICE-Ovarian01 will assess 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 objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary endpoints include ORR as assessed by investigator, duration of response (DoR), progression free survival (PFS) and disease control rate (DCR) – all assessed by both BICR and investigator – and overall survival (OS).

The phase 3 part of REJOICE-Ovarian01 will assess the efficacy and safety of raludotatug deruxtecan at the selected dose compared to investigator’s 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.

The trial is expected to enroll approximately 650 patients across Asia, Europe, North America and South America. For more information, please visit ClinicalTrials.gov.

About Ovarian Cancer

More than 324,000 women were diagnosed with ovarian cancer worldwide in 2022.^6,7 Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens.¹ The median overall survival for advanced ovarian cancer following recurrence is approximately two years, with a five-year survival rate of less than 30%.^2,3 For patients that develop resistance to platinum-based chemotherapy, treatment options are limited.⁸

The 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.⁹

About CDH6

CDH6 (human cadherin-6) is a cadherin family protein overexpressed in several cancers, including ovarian tumors.⁴ An estimated 65% to 85% of patients with ovarian cancer have tumors that express CDH6, which is associated with poor prognosis.^4,5 There is currently no CDH6 directed therapy approved for treatment of any cancer.

About Raludotatug Deruxtecan

Raludotatug deruxtecan (R-DXd) is an investigational, potential first-in-class CDH6 directed ADC. Designed using Daiichi Sankyo’s 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.

In addition to the REJOICE-Ovarian01 trial, raludotatug deruxtecan is being evaluated in a phase 1 trial in advanced ovarian cancer as part of a strategic collaboration with Sarah Cannon Research Institute (SCRI) with study operational oversight and delivery provided through SCRI’s early phase oncology clinical research organization, SCRI Development Innovations in Nashville, TN.

About the Daiichi Sankyo and Merck Collaboration

Daiichi Sankyo and Merck entered into a global collaboration in October 2023 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.

About the DXd ADC Portfolio of Daiichi Sankyo

The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo.

Designed using Daiichi Sankyo’s proprietary DXd ADC Technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, 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.

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo

Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical needs. For more information, please visit www.daiichisankyo.com.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

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 – 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 and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” 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’s 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.

Risks 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’s 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’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The 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’s Annual Report on Form 10-K for the year ended December 31, 2023 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

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References:

¹ Pignata S, et al. Ann Oncol. 2017 Nov 1;28(suppl_8):viii51-viii56.

² Shimokawa M, et al. J Cancer. 2018; 9(5):872.

³ Colombo N, et al. Int J Gynecol Cancer. 2017 Jul 1; 27(6).

⁴ Bartolome RA, et al. Mol Oncol. 2021 Jul; 15(7): 1849-18865.

⁵ Shintani D, et al. Gynecol Oncol. 2022;166(Suppl 1): S116.

⁶ Global Cancer Observatory. Population Fact Sheet. Updated 2022. Accessed March 2024.

⁷ SEER Cancer Stat Facts: Ovarian Cancer. Data from SEER 18 2011-2017.

⁸ Mor G, et al. Cancer biology & therapy. 2011;11(8), 708–713.

⁹ Kurnit K, et al. Obstetrics and Gynecology. 2021; 137(1): 108-121.

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