Biohaven's BHV-1510 Shows Promising Efficacy in Phase 1 Trial Combining Trop2 ADC with Cemiplimab
核心洞察
Biohaven (搜索)'s next-generation Trop2 (搜索) antibody-drug conjugate BHV-1510 demonstrated a 72.7% confirmed objective response rate when combined with cemiplimab at the optimal dose of 2.5 mg/kg Q3W.
The combination therapy showed particularly strong activity in endometrial cancer (搜索) with 100% response rate and 60% response rate in non-small cell lung cancer (搜索) among pretreated patients.
BHV-1510 exhibited a differentiated safety profile with no cases of interstitial lung disease and low rates of hematological toxicities compared to other Trop2 (搜索) ADCs.
Biohaven (搜索) Ltd. presented encouraging Phase 1 clinical data for BHV-1510, a next-generation trophoblast cell surface antigen 2 (Trop2 (搜索)) directed antibody-drug conjugate (ADC), in combination with Regeneron's anti-PD-1 (搜索) cemiplimab at the 2025 European Society for Medical Oncology (ESMO) Immuno-Oncology Congress in London. The combination demonstrated notable efficacy across multiple solid tumor types in a heavily pretreated patient population.
Strong Response Rates Across Multiple Tumor Types
At the optimal dose of BHV-1510 2.5 mg/kg every three weeks (Q3W) combined with cemiplimab, the confirmed objective response rate (ORR) reached 72.7%. The combination showed particularly impressive activity in endometrial cancer (搜索) with a 100% response rate (4/4 patients), including one complete response. Non-small cell lung cancer (搜索) (NSCLC) patients achieved a 60% response rate (3/5 patients), while urothelial cancer (搜索) showed a 50% response rate (1/2 patients).
Across all 23 efficacy-evaluable participants treated with the combination therapy at various dose levels, the confirmed ORR was 52.2% as of the October 10, 2025 clinical cutoff date. This included responses in 42.9% of NSCLC patients (6/14), 66.7% of endometrial cancer (搜索) patients (4/6), and 50% of urothelial cancer (搜索) patients (1/2). A confirmed response was also reported in the participant with triple negative breast cancer (搜索).
"We are excited by this emerging data and the potential synergy of BHV-1510 with cemiplimab," stated Dr. Ida Micaily, Principal Investigator and Assistant Professor at Sidney Kimmel Comprehensive Cancer Center at Jefferson. "The early responses we are observing in these difficult-to-treat tumors—despite patients having received prior therapies, including other PD-1 (搜索)/PD-L1 agents—are particularly encouraging."
Durable Responses in Challenging Patient Population
The study enrolled a heavily pretreated population with a median of two prior lines of therapy for advanced/metastatic disease. Notably, 87.1% of participants had prior PD-(L)1 exposure, with 51.6% receiving a PD-(L)1 agent as their most recent treatment before study enrollment. Despite this challenging patient population, the majority of participants experienced tumor reduction on their first scan, with a median time to response of 11.1 weeks.
The durability of responses appears promising, with 18 participants continuing study treatment at the time of clinical cutoff and patients remaining on therapy beyond six months. "We also have patients remaining on therapy beyond six months, suggesting the potential for durable disease control," Dr. Micaily noted.
Differentiated Safety Profile
BHV-1510 demonstrated a safety profile that distinguishes it from other Trop2 (搜索) ADCs currently in development. The maximum tolerated dose was not reached, with only one participant experiencing a dose-limiting toxicity of Grade 3 stomatitis at the 2.75 mg/kg Q3W dose. A total of 31 participants were treated with the combination, receiving BHV-1510 doses ranging from 2-2.75 mg/kg Q3W and 1.25-1.5 mg/kg on days 1 and 8 every three weeks, combined with cemiplimab at 350 mg Q3W.
The rate of neutrophil count decrease was notably low and manageable, with all-grade events occurring in 12.9% of patients and Grade ≥3 events in only 6.5%. Treatment-emergent diarrhea and alopecia rates were similarly low at 6.5% (0% Grade ≥3) and 9.7%, respectively. The most frequent toxicity was oral mucositis/stomatitis, occurring in 59.1% of patients (22.7% Grade ≥3) in the Q3W regimen and 33.3% (11.1% Grade ≥3) in the twice-weekly regimen.
Importantly, no cases of interstitial lung disease were observed, and no participants discontinued treatment due to adverse events. Treatment-emergent serious adverse events were reported in four participants, none of which were related to study treatment.
Novel TopoIx Payload Technology
BHV-1510 incorporates Biohaven (搜索)'s proprietary TopoIx payload, which appears to contribute to its favorable safety profile. The pharmacokinetic analysis revealed that the unconjugated payload concentration was low, with a payload-to-ADC molar ratio of less than 1%, indicating high stability of the ADC in circulation.
"These findings—together with the early promising efficacy, differentiated safety profile, lack of payload-related toxicity, enabled by our novel TopoIx payload and stable linker technology—underscores the potential for BHV-1510 to move into earlier lines of therapy, in particular with checkpoint inhibitor combinations, for these challenging tumor types," commented Dr. Nushmia Khokhar, Chief Medical Officer of Oncology at Biohaven (搜索).
Clinical Development Implications
The encouraging preliminary data suggest potential for BHV-1510 to advance into earlier lines of therapy, particularly in combination with checkpoint inhibitors. The combination's activity in patients who had progressed on prior PD-(L)1 therapy indicates potential synergistic mechanisms between the Trop2 (搜索)-targeted ADC and immune checkpoint inhibition.
The Phase 1 study continues to enroll patients, with the poster presentation (252P) made available at the ESMO Immuno-Oncology Congress. The data support continued development of this combination approach for patients with advanced solid tumors (搜索) expressing Trop2 (搜索).