Trial results for the Phase 1/2 study (NCT03474497) evaluating pembrolizumab in combination with IL-2 and radiotherapy in patients with advanced cancers refractory to checkpoint blockade were posted on ClinicalTrials.gov on 2026-01-29. The study reported an Overall Response Rate (ORR) in 2 participants and a Disease Control Rate (DCR) in 5 participants among the enrolled patients. The median Progression Free Survival (PFS) was observed to be 2.03 months.
Background
The study (UCDCC#272) investigated a combinatorial approach involving IL-2, radiotherapy, and pembrolizumab. This approach was evaluated in patients with histologically proven metastatic Non Small Cell Lung Cancer, Metastatic Melanoma, Metastatic Renal Cell Carcinoma, or Head and Neck Squamous Cell Carcinoma who had previously failed PD-1 / PD-L1 checkpoint blockade therapy. The primary objective was to assess the safety and toxicity of this combination.
Trial design
The UCDCC#272 study (NCT03474497) was a Phase 1/2 trial with an enrollment of 18 participants. The study included patients over 18 years of age with metastatic Non Small Cell Lung Cancer, Metastatic Melanoma, Metastatic Renal Cell Carcinoma, or Head and Neck Squamous Cell Carcinoma who had experienced progression after prior PD-1 / PD-L1 checkpoint blockade therapy. Patients were required to have a candidate treatment lesion accessible for radiotherapy and serial intralesional injections, as well as at least one distinct target lesion. The study aimed to evaluate the safety and toxicity of the combinatorial approach.
Key results
The trial results for the Pembrolizumab/IL-2/Radiotherapy group included several key measurements:
- The Abscopal Response Rate (ARR) was observed in 2 Participants.
- The Overall Response Rate (ORR) was observed in 2 Participants.
- The Disease Control Rate (DCR) was observed in 5 Participants.
- The median Progression Free Survival (PFS) was 2.03 months. The dispersion type was noted as 95% Confidence Interval.
- The Maximum Tolerated Dose (MTD) determined in Phase 1 was 15 x 10^6 International units (IU).
- Regarding the Safety Profile and Toxicity, 6 Participants were noted.
What this means
The results from this Phase 1/2 study provide initial insights into the safety and preliminary activity of combining pembrolizumab with IL-2 and radiotherapy in patients with advanced cancers that have progressed despite prior PD-1 / PD-L1 checkpoint blockade therapy. The observation of an Overall Response Rate in 2 participants and a Disease Control Rate in 5 participants suggests that this combinatorial strategy may elicit anti-tumor activity in a population with limited treatment options. The determination of a Maximum Tolerated Dose of 15 x 10^6 International units (IU) for the IL-2 component is important for guiding future clinical development of this regimen. These findings warrant further investigation into the potential benefits and risks of this combination.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03474497, titled "UCDCC#272: IL-2, Radiotherapy, and Pembrolizumab in Patients Refractory to Checkpoint Blockade," were posted on 2026-01-29 on clinicaltrials.gov.