Trial results for Pembrolizumab in combination with investigational agents for advanced non-small cell lung cancer (NSCLC) were posted on ClinicalTrials.gov on 2026-05-13. The Phase 2 KEYMAKER-U01 Substudy 3 evaluated Pembrolizumab with boserolimab, MK-4830, or MK-0482 in patients previously treated with anti-PD-L1 therapy. Among the combinations, Pembrolizumab plus MK-4830 showed an objective response rate (ORR) of 11.1%.
Background
The study investigated Pembrolizumab (MK-3475) in combination with investigational agents boserolimab (MK-5890), MK-4830, and MK-0482. This research focused on participants with advanced squamous or non-squamous non-small cell lung cancer (NSCLC) who had been previously treated with anti-programmed cell death receptor ligand 1 (PD-L1) therapy. This study was conducted as one of three Pembrolizumab substudies under the KEYMAKER-U01 umbrella master protocol.
Trial design
The Phase 2 KEYMAKER-U01 Substudy 3 (NCT04165096) enrolled 128 participants with advanced non-small cell lung cancer (NSCLC). The study's purpose was to assess the efficacy and safety of Pembrolizumab in combination with boserolimab, MK-4830, or MK-0482. All participants had previously received anti-PD-L1 therapy.
Key results
The trial results included objective response rate (ORR) and progression-free survival (PFS) according to RECIST 1.1, as well as adverse event data:
- For Objective Response Rate (ORR):
- Pembrolizumab + Boserolimab: 5.4% of participants
- Pembrolizumab + MK-4830: 11.1% of participants
- Pembrolizumab + MK-0482: 4.4% of participants
- For Progression-Free Survival (PFS):
- Pembrolizumab + Boserolimab: Median 2.5 months
- Pembrolizumab + MK-4830: Median 2.4 months
- Pembrolizumab + MK-0482: Median 2.3 months
- Regarding Adverse Events (AEs):
- 100% of participants in the Pembrolizumab + Boserolimab group experienced one or more AEs.
- 93.3% of participants in the Pembrolizumab + MK-4830 group experienced one or more AEs.
- 91.1% of participants in the Pembrolizumab + MK-0482 group experienced one or more AEs.
- Regarding Discontinuation Due to AEs:
- 16.2% of participants in the Pembrolizumab + Boserolimab group discontinued treatment.
- 17.8% of participants in the Pembrolizumab + MK-4830 group discontinued treatment.
- 6.7% of participants in the Pembrolizumab + MK-0482 group discontinued treatment.
What this means
These Phase 2 results indicate varying efficacy signals for Pembrolizumab in combination with different investigational agents in advanced NSCLC patients previously treated with anti-PD-L1 therapy. The Pembrolizumab + MK-4830 combination showed the highest objective response rate at 11.1%, while PFS medians across all three combinations were similar, ranging from 2.3 to 2.5 months. The high rates of adverse events (91.1% to 100%) and treatment discontinuations due to AEs (6.7% to 17.8%) suggest that these combinations were associated with notable toxicity. These findings provide initial efficacy and safety data for these specific combinations in a challenging patient population, which may inform future development strategies.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04165096, titled 'KEYMAKER-U01 Substudy 3: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Participants With Advanced Non-small Cell Lung Cancer (NSCLC), Previously Treated With Anti-programmed Cell Death Receptor Ligand 1 (PD-L1) Therapy (MK-3475-01C/KEYMAKER-U01C)', were posted on 2026-05-13 on clinicaltrials.gov.