Daiichi Sankyo and Merck Advance Promising Ovarian Cancer ADC to Phase 3 Trial

Daiichi Sankyo and Merck & Co. have reported encouraging phase 2 data for their antibody-drug conjugate (ADC) raludotatug deruxtecan (R-DXd) in ovarian cancer, paving the way for the treatment's advancement to a pivotal phase 3 trial. The results, presented at the 2025 European Society for Medical Oncology (ESMO) Congress, demonstrate the potential of this novel therapy in addressing the unmet needs of patients with recurrent, platinum-resistant ovarian cancer.

Phase 2 Trial Results Show Promise

The phase 2 trial evaluated three doses of R-DXd in 107 patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer resistant to platinum chemotherapy. Across all doses, the confirmed overall response rate (ORR) was 50.5%, with three patients achieving complete responses and 51 patients showing partial responses. The disease control rate reached 77.6%.

Dr. Abderrahmane Laadem, head of late-stage clinical development at Daiichi, commented that "50% with rapid response is within the ballpark of what we expect in this highly chemo-resistant population." The highest ORR of 57.1% was observed in patients receiving the top dose of R-DXd.

Strategic Dose Selection for Phase 3

Despite the highest ORR being associated with the top dose, Daiichi and Merck have opted to advance the middle 5.6-mg/kg dose into the phase 3 portion of the trial. This decision follows a careful evaluation of efficacy and safety data, including the management of interstitial lung disease (ILD), a known toxicity of Daiichi's ADCs.

The phase 2 trial reported four treatment-related ILD/pneumonitis events, with only one case of grade 3 or worse, observed in the low-dose cohort. Dr. Laadem noted that the tolerability profile was as expected, with the "very low" rate of ILD being a positive surprise.

Future Directions and Competitive Landscape

The success of R-DXd in ovarian cancer, coupled with Keytruda's recent positive results in the same indication, opens up opportunities for combination therapy. The partners plan to compare R-DXd to the investigator's choice of chemotherapy in the phase 3 monotherapy trial, while also exploring potential combinations with Keytruda to improve outcomes and move into earlier lines of treatment.

Daiichi and Merck's development of R-DXd extends beyond ovarian cancer, with ongoing trials in other tumor types associated with CDH6 expression. This broad program positions the partners at the forefront of efforts to target this receptor with ADCs. Other companies developing CDH6-directed ADCs include OnCusp Therapeutics, NextCure, and Phrontline Biopharma, with the latter focusing on a bispecific CDH6 ADC.

As the survival data for R-DXd continue to mature, the pharmaceutical industry will be closely watching to see how this promising therapy shapes the future of ovarian cancer treatment and the broader landscape of targeted cancer therapies.