Trial results for a Phase 1b/2 study investigating E7386 in combination with pembrolizumab in previously treated participants with selected solid tumors were posted on ClinicalTrials.gov on 2025-10-24. The Phase 2 part reported objective response rates (ORR) of 6.9% in melanoma, 3.2% in colorectal cancer (CRC), and 0.0% in hepatocellular carcinoma (HCC).
Background
Pembrolizumab (Keytruda) is an immune checkpoint inhibitor approved for various cancers. This study investigated its combination with the investigational agent E7386 in previously treated participants with melanoma, hepatocellular carcinoma, and colorectal neoplasms.
Trial design
The Phase 1b/Phase 2 study (NCT05091346) enrolled 89 participants. Phase 1b assessed safety and tolerability of E7386 with pembrolizumab and determined the recommended Phase 2 dose. Phase 2 evaluated objective response rate (ORR) of the combination in melanoma, colorectal cancer, and hepatocellular carcinoma, with an additional arm including lenvatinib for HCC.
Key results
The trial reported safety and efficacy outcomes. In the Phase 1b dose escalation part, evaluating safety and tolerability of E7386 in combination with pembrolizumab, 0 dose-limiting toxicities (DLTs) were reported for both the E7386 100 mg + Pembrolizumab 200 mg and E7386 120 mg + Pembrolizumab 200 mg groups. The percentage of participants with best overall response (BOR) in Phase 1b was 0% for both tested dose combinations.
In the Phase 2 dose expansion part, evaluating objective response rate (ORR) for E7386 120 mg + Pembrolizumab 200 mg:
- For hepatocellular carcinoma (HCC), the ORR was 0.0% (95% Confidence Interval).
- For melanoma, the ORR was 6.9% (95% Confidence Interval).
- For colorectal cancer (CRC), the ORR was 3.2% (95% Confidence Interval).
What this means
The Phase 1b results suggest the combination of E7386 and pembrolizumab was generally tolerable, with 0 dose-limiting toxicities. However, Phase 2 efficacy showed low objective response rates: 6.9% in melanoma, 3.2% in colorectal cancer, and 0.0% in hepatocellular carcinoma, indicating limited clinical activity in these previously treated patient populations.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05091346, titled "A Study of E7386 in Combination With Pembrolizumab in Previously Treated Participants With Selected Solid Tumors," were posted on 2025-10-24 on clinicaltrials.gov.