Daiichi Sankyo and Merck Advance Ovarian Cancer ADC to Phase 3 Trial After Promising Phase 2 Results

Daiichi Sankyo and Merck & Co. have reported encouraging phase 2 data for their antibody-drug conjugate (ADC) raludotatug deruxtecan (R-DXd) in recurrent 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 CDH6-directed therapy in addressing a significant unmet need in ovarian cancer treatment.

Phase 2 Trial Results Show Promising Efficacy

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 experiencing partial responses. The disease control rate reached an impressive 77.6%.

Dr. Abderrahmane Laadem, head of late-stage clinical development at Daiichi, commented on the results, stating 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. However, the partners have opted to advance the middle 5.6-mg/kg dose to the phase 3 portion of the trial, which demonstrated an ORR of 50% and included two complete responses.

Safety Profile and Future Directions

The safety profile of R-DXd appears manageable, with interstitial lung disease (ILD) remaining a focus of attention. Four treatment-related ILD/pneumonitis events were reported in the phase 2 trial, with only one case being grade 3 or higher. Dr. Laadem noted that the "very low" rate of ILD was a positive surprise, given it is a known toxicity of Daiichi's ADCs.

Looking ahead, the partners plan to compare R-DXd to the investigator's choice of chemotherapy in the phase 3 portion of the monotherapy trial. Additionally, Merck has discussed the potential to combine the ADC with its immunotherapy drug Keytruda to improve outcomes and potentially move into earlier lines of treatment.

Competitive Landscape and Market Implications

The development of R-DXd positions Daiichi Sankyo and Merck at the forefront of CDH6-directed ADC therapies. Other companies with CDH6-targeted ADCs in development include OnCusp Therapeutics, NextCure (which licensed an asset from Simcere Zaiming), and Phrontline Biopharma, which is developing a bispecific CDH6 ADC.

The partnership between Daiichi Sankyo and Merck, initiated with a $750 million upfront payment from Merck for rights to R-DXd, underscores the significant potential of this therapy. As survival data mature and the phase 3 trial progresses, the pharmaceutical industry will be closely watching the development of R-DXd and its potential impact on the treatment landscape for ovarian cancer.