Daiichi Sankyo and Merck & Co. have reported midphase ovarian cancer data, clearing the partners to advance the antibody-drug conjugate into the phase 3 part of the trial.
The phase 2 trial tested three doses of the CDH6-directed ADC raludotatug deruxtecan (R-DXd) in people with recurrent ovarian, primary peritoneal or fallopian tube cancer that was resistant to platinum chemotherapy. Daiichi reported a 46% overall response rate (ORR) in patients with previously treated ovarian cancer in 2023.
Merck, which paid an initial $750 million for rights to R-DXd, and Daiichi used the 2025 European Society for Medical Oncology (ESMO) Congress to report that the ORR seen in the phase 1 study held up in a larger trial. Across three doses and 107 patients, the partners saw a confirmed ORR of 50.5%.
Abderrahmane Laadem, M.D., head of late-stage clinical development at Daiichi, told Fierce at ESMO that “50% with rapid response is within the ballpark of what we expect in this highly chemo-resistant population.” Three participants had complete responses, and 51 patients had partial responses. The disease control rate was 77.6%.
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Daiichi and Merck saw the highest ORR—57.1%—in patients who received the top dose of R-DXd. Yet the drugmakers have opted to take the middle 5.6-mg/kg dose into the phase 3 part of the trial. The ORR on the phase 3 dose was 50% and included two complete responses.
The decision continues the partners’ pullback from higher doses of R-DXd. Daiichi tested a higher dose in phase 1. The deaths of two patients from interstitial lung disease (ILD) at the maximum phase 1 dose led the partners to choose a lower maximum dose for phase 2.
Daiichi and Merck saw four treatment-related ILD/pneumonitis events in the phase 2 trial. Two cases were in the top-dose cohort. Both those cases were low grade, as was the one case on the phase 3 dose. The only grade 3 or worse ILD case was seen on the low dose. Laadem said the tolerability profile was as expected, with the “very low” rate of ILD—a known toxicity of Daiichi’s ADCs—a positive surprise.
The data, coupled with Keytruda’s recent success in ovarian cancer, open up a combination therapy opportunity. The partners plan to compare R-DXd to the investigator’s choice of chemotherapy in the phase 3 part of the monotherapy trial. Merck has also discussed (PDF) the potential to combine the ADC with Keytruda to improve outcomes and move into earlier lines of treatment.
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Daiichi and Merck are testing R-DXd in other tumor types associated with CDH6 expression, establishing a broad program that puts the partners at the forefront of efforts to aim ADCs at the receptor. Other companies with CDH6-directed ADCs in development include OnCusp Therapeutics and NextCure, which licensed an asset from Simcere Zaiming. Phrontline Biopharma is developing a bispecific CDH6 ADC.
The ORR for R-DXd has set the bar for the competition. Exactly how high the bar is will become clearer as the survival data mature. Daiichi and Merck only had around five months of follow-up as of the cutoff date.
Editor’s note: James Waldron contributed to the reporting in this article.
