Trial results for Pembrolizumab (Keytruda) in combination with GEN1042 and radiotherapy were posted on 2026-07-02. The PHASE1/PHASE2 study, which included participants with metastatic solid tumors, reported an Objective Response Rate (ORR) of 14.3% for the triple combination, with no dose-limiting toxicities (DLTs) observed in either treatment arm.
Background
Pembrolizumab is an immunotherapy agent. This trial aimed to assess the safety and clinical activity of immunoradiotherapy combinations as a treatment option for participants with metastatic solid tumors. The study specifically investigated GEN1042 in combination with radiotherapy, and GEN1042 in combination with radiotherapy and Pembrolizumab.
Trial design
The study, identified as NCT05491317, was a PHASE1/PHASE2 trial that was ultimately TERMINATED. It enrolled 13 participants with Non-CNS Tumor, specifically metastatic solid tumors. The trial evaluated two main intervention arms: Part 1 Cohort 1 received 27Gy Stereotactic Body Radiotherapy (SBRT) + GEN1042, while Part 1 Cohort 2 received 27Gy SBRT + GEN1042 + Pembrolizumab.
Key results
Regarding safety, the Number of Participants With Dose Limiting Toxicities (DLTs) was 0 Participants in both the Part 1 Cohort 1: 27Gy SBRT + GEN1042 group and the Part 1 Cohort 2: 27Gy SBRT + GEN1042 + Pembrolizumab group.
For efficacy, the Objective Response Rate (ORR) was 0 percentage of participants for Part 1 Cohort 1: 27Gy SBRT + GEN1042. In contrast, Part 1 Cohort 2: 27Gy SBRT + GEN1042 + Pembrolizumab showed an ORR of 14.3 percentage of participants. The Duration of Response (DOR) for Part 1 Cohort 2: 27Gy SBRT + GEN1042 + Pembrolizumab was a median of 3.02 months.
The Disease Control Rate (DCR) was 66.7 percentage of participants for Part 1 Cohort 1: 27Gy SBRT + GEN1042 and 42.9 percentage of participants for Part 1 Cohort 2: 27Gy SBRT + GEN1042 + Pembrolizumab. Progression Free Survival (PFS) was a median of 2.8 months for Part 1 Cohort 1: 27Gy SBRT + GEN1042 and 2.6 months for Part 1 Cohort 2: 27Gy SBRT + GEN1042 + Pembrolizumab.
The Overall Survival (OS) was a median of 7.4 months for Part 1 Cohort 1: 27Gy SBRT + GEN1042, while the median OS for Part 1 Cohort 2: 27Gy SBRT + GEN1042 + Pembrolizumab was NA months. The Number of Participants With Abscopal Response in non-irradiated target lesions was 0 Participants in Part 1 Cohort 1: 27Gy SBRT + GEN1042.
What this means
The preliminary results from this early-phase trial suggest that the combination of Pembrolizumab, GEN1042, and radiotherapy may induce an Objective Response Rate in some participants with metastatic solid tumors, specifically 14.3%, without introducing additional dose-limiting toxicities. While the ORR was higher in the Pembrolizumab combination arm compared to GEN1042 alone, other efficacy measures like DCR and PFS were numerically lower in the combination arm. The trial's termination and small enrollment of 13 participants indicate these findings are very early and require further investigation.
Source
These trial results were posted on ClinicalTrials.gov on 2026-07-02. The full details of the study, NCT05491317, are available on clinicaltrials.gov.