Daiichi Sankyo and Merck's Ovarian Cancer ADC Advances to Phase 3 Trial After Promising Midphase Results

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 CDH6-directed therapy in addressing the unmet needs of patients with recurrent, platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers.

Phase 2 Trial Results Show Promising Efficacy

The phase 2 trial evaluated three doses of R-DXd in 107 patients with previously treated ovarian cancer. 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%, indicating the drug's potential to manage tumor growth effectively.

Dr. Abderrahmane Laadem, head of late-stage clinical development at Daiichi Sankyo, 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 chosen to advance the middle 5.6-mg/kg dose into the phase 3 portion of the trial, which demonstrated an ORR of 50% and included two complete responses.

Safety Profile and Dose Selection

The decision to proceed with the middle dose reflects a cautious approach following safety concerns in earlier studies. In phase 1, two patient deaths due to interstitial lung disease (ILD) at the maximum dose led to the selection of lower doses for phase 2.

In the current phase 2 trial, four treatment-related ILD/pneumonitis events were reported, with only one case being grade 3 or worse. Dr. Laadem noted that the tolerability profile was as expected, with the "very low" rate of ILD being a positive surprise, given that it is a known toxicity of Daiichi's ADCs.

Future Directions and Combination Potential

The positive results from this trial, coupled with Keytruda's recent success in ovarian cancer, open up possibilities for combination therapy. While the phase 3 portion of the trial will compare R-DXd to the investigator's choice of chemotherapy, Merck has also discussed the potential to combine the ADC with Keytruda to improve outcomes and potentially move into earlier lines of treatment.

Daiichi and Merck are also exploring R-DXd's potential in other tumor types associated with CDH6 expression, positioning themselves at the forefront of ADC development targeting this receptor. The partnership, which began with Merck's $750 million initial payment for rights to R-DXd, reflects the growing interest in ADC technology within the oncology field.

As the survival data continue to mature, the pharmaceutical industry will be watching closely to see how R-DXd's performance sets the bar for competing CDH6-directed ADCs in development by companies such as OnCusp Therapeutics, NextCure, and Phrontline Biopharma.