Merck and Daiichi's Raludotatug Deruxtecan Shows 51% Response Rate in Platinum-Resistant Ovarian Cancer
核心洞察
Raludotatug deruxtecan achieved a 51% confirmed overall response rate across three doses in 107 platinum-resistant ovarian cancer (搜索) patients in the phase 2 portion of the Rejoice-Ovarian01 trial.
The 5.6mg/kg dose was selected for phase 3 testing based on optimal risk-benefit profile, showing 50% response rate with manageable safety concerns.
Treatment-related interstitial lung disease (搜索) occurred in patients across dose levels, including one grade 3 case at the lowest 4.8mg/kg dose, highlighting ongoing safety considerations.
Merck & Co (搜索) and Daiichi Sankyo reported encouraging results for their CDH6 (搜索)-targeting antibody-drug conjugate raludotatug deruxtecan in platinum-resistant ovarian cancer (搜索), with data from the phase 2 portion of the Rejoice-Ovarian01 trial presented at ESMO showing a 51% confirmed overall response rate across 107 patients.
The results represent a meaningful improvement over the 46% confirmed ORR observed in an earlier phase 1 trial with 50 late-line ovarian cancer patients, providing validation for the ADC's therapeutic potential in this challenging patient population.
Dose Optimization Results
The phase 2 dose-optimization portion of Rejoice-Ovarian01 evaluated three dose levels: 4.8mg/kg, 5.6mg/kg, and 6.4mg/kg. Investigators concluded that 5.6mg/kg provided the optimal risk-benefit profile, achieving a 50% ORR while maintaining manageable safety.
The dose selection comes as Merck and Daiichi work to advance raludotatug deruxtecan following setbacks with another ADC from their $5.5 billion upfront licensing deal - patritumab deruxtecan, which recently failed in lung cancer (搜索).
Safety Profile Considerations
Treatment-related interstitial lung disease (搜索), a known toxicity associated with deruxtecan payloads, emerged as a key safety concern across dose levels. Any-grade interstitial lung disease was observed in two patients receiving 6.4mg/kg, while one grade 3 case occurred at the lowest tested dose of 4.8mg/kg, indicating that lower doses do not eliminate this risk entirely.
The safety findings echo concerns from the earlier phase 1 trial, where the highest dose of 8.0mg/kg was discontinued after two patients died from interstitial lung disease (搜索).
Phase 3 Trial Design
The phase 3 portion of Rejoice-Ovarian01 will evaluate raludotatug deruxtecan at the selected 5.6mg/kg dose versus physician's choice of chemotherapy in platinum-resistant ovarian cancer (搜索) patients. The trial employs co-primary endpoints of overall response rate and progression-free survival.
Critical data on progression-free survival and duration of response from the phase 2 portion are not yet mature, leaving important questions about the durability of responses unanswered.
Competitive Landscape Context
The results position raludotatug deruxtecan among a limited field of CDH6 (搜索)-targeting therapies in clinical development. NextCure recently acquired SIM0505, another CDH6-targeting project, for a significantly smaller $12 million upfront payment compared to Merck's substantial investment.
Merck is simultaneously awaiting an FDA decision on Keytruda plus chemotherapy in platinum-resistant ovarian cancer (搜索) following positive results from the Keynote-B96 trial, potentially providing the company with multiple treatment options in this indication.