Trial results for the Phase 2 study NCT05179603, investigating pembrolizumab in combination with SAR444245 (pegenzileukin) for adults and adolescents with relapsed or refractory B-cell lymphoma, were posted on ClinicalTrials.gov on 2025-10-02. In Cohort A, the combination therapy demonstrated an objective response rate (ORR) of 92.9% and a complete response rate (CRR) of 71.4%.
Background
The study investigated pembrolizumab, an anti-PD-1 therapy, in combination with SAR444245 (pegenzileukin) for the treatment of relapsed or refractory B-cell lymphoma. The specific conditions studied included Classic Hodgkin Lymphoma and Diffuse Large B-cell Lymphoma.
Trial design
The study NCT05179603, titled "A Study of SAR444245 With or Without Other Anticancer Therapies for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Lymphoma (Master Protocol) [Pegathor Lymphoma 205]," was a Phase 2, multi-cohort, un-controlled, non-randomized, open-label, multi-center study. It enrolled 14 participants aged 12 years and older with relapsed or refractory B-cell lymphoma, specifically Classic Hodgkin Lymphoma and Diffuse Large B-cell Lymphoma. The study was structured as a master protocol, with Substudy 1-Cohort A specifically assessing the combination of Pegenzileukin 24 μg/kg + Pembrolizumab. The trial was officially TERMINATED.
Key results
Results from Cohort A, which investigated Pegenzileukin 24 μg/kg + Pembrolizumab, showed the following:
- The Complete Response Rate (CRR) was 71.4% (percentage of participants).
- The Objective Response Rate (ORR) was 92.9% (percentage of participants).
- The Clinical Benefit Rate (CBR) was 92.9% (percentage of participants).
- The median Time to Response (TTR) was 2.0 months.
- All 14 participants experienced Treatment-Emergent Adverse Events (TEAEs), and 5 participants experienced Treatment-Emergent Serious Adverse Events (TESAEs).
- 1 participant experienced Dose Limiting Toxicities (DLTs).
Plasma concentrations of Pegenzileukin were also measured:
- Mean plasma concentration was 191.7 ng/mL (Standard Deviation: 78.4).
- Another mean plasma concentration measurement was 95.2 ng/mL (Standard Deviation: 75.8).
- The mean Concentration at End of Infusion (Ceoi) of Pegenzileukin was 438.2 ng/mL (Standard Deviation: 238.6).
The median Duration of Response (DoR) and median Progression Free Survival (PFS) were reported as NA with a 90% Confidence Interval.
What this means
The high objective response rate and complete response rate observed in this Phase 2 study suggest that the combination of pembrolizumab with pegenzileukin may offer a promising therapeutic option for patients with relapsed or refractory B-cell lymphoma, including Classic Hodgkin Lymphoma and Diffuse Large B-cell Lymphoma. While the trial was terminated, these initial efficacy signals warrant further investigation into the potential of this combination, particularly given the unmet need in this patient population. The safety profile, with all participants experiencing TEAEs, indicates that careful management of adverse events would be crucial in future studies.
Source
The information for this article was sourced from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05179603, titled "A Study of SAR444245 With or Without Other Anticancer Therapies for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Lymphoma (Master Protocol) [Pegathor Lymphoma 205]," were posted on 2025-10-02 on clinicaltrials.gov.