Trial results for the Phase 2 study (NCT05256381) investigating pembrolizumab in combination with nanrilkefusp alfa for advanced solid tumors were posted on ClinicalTrials.gov on 2025-11-17. The study was terminated, with objective response rates varying significantly across tumor types, including 33.3% in colorectal cancer and 0% in hepatocellular carcinoma.
Background
Pembrolizumab (Keytruda) is an immune checkpoint inhibitor approved for various cancers. This study investigated its combination with nanrilkefusp alfa in patients with selected advanced solid tumors, aiming to evaluate the antitumor efficacy of this therapeutic approach.
Trial design
The study (NCT05256381) was a Phase 2 trial that enrolled 166 participants with selected advanced solid tumors. The conditions investigated included Non-Small Cell Lung Cancer, Colorectal Cancer, Cutaneous Squamous Cell Carcinoma, Hepatocellular Carcinoma, Castration-resistant Prostate Cancer, and Ovarian Cancer. The trial investigated nanrilkefusp alfa in combination with pembrolizumab. Its primary objective was to estimate the antitumor efficacy of this combination. The study was ultimately terminated.
Key results
The trial results reported objective response rates (ORR) according to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) for various tumor types:
- For Non-small Cell Lung Cancer, the ORR was 5.1%.
- For Colorectal Cancer, the ORR was 33.3%.
- For Cutaneous Squamous Cell Carcinoma, the ORR was 27.3%.
- For Hepatocellular Carcinoma, the ORR was 0%.
- For Metastatic Castration-resistant Prostate Cancer, the ORR was 10.0%.
- For Ovarian Cancer, the ORR was 11.4%.
Regarding safety, the number of patients with a treatment-emergent adverse event (TEAE) was reported for each tumor group:
- Non-small Cell Lung Cancer: 40 Participants
- Colorectal Cancer: 8 Participants
- Cutaneous Squamous Cell Carcinoma: 12 Participants
- Hepatocellular Carcinoma: 12 Participants
- Metastatic Castration-resistant Prostate Cancer: 54 Participants
- Ovarian Cancer: 39 Participants
What this means
The varied objective response rates across different advanced solid tumor types, coupled with the termination of the study, indicate mixed efficacy signals for the combination of nanrilkefusp alfa and pembrolizumab. While some tumor types like colorectal cancer showed a notable response rate, others, such as hepatocellular carcinoma, showed no objective responses. The termination of this Phase 2 study suggests that the overall benefit-risk profile or specific efficacy thresholds may not have been met to warrant further development in all investigated indications.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05256381, titled "A Study of SOT101 in Combination With Pembrolizumab to Evaluate the Efficacy and Safety in Patients With Selected Advanced Solid Tumors," were posted on 2025-11-17 on clinicaltrials.gov.