Pembrolizumab monotherapy for melanoma or non-small cell lung cancer in India: Results of the phase IV keynote-593 study.

e21518 Background: The PD-1 inhibitor pembrolizumab has been shown to provide a significant overall survival (OS) benefit with manageable safety in global clinical studies of advanced melanoma and non-small cell lung cancer (NSCLC); however, these trials did not include any participants from India. KEYNOTE-593 (NCT03715205) is a prospective, open-label, phase IV study designed to evaluate the safety of pembrolizumab in participants from India with advanced melanoma or NSCLC. Methods: Eligible participants had unresectable stage III or IV melanoma and ≤1 prior line of systemic therapy; stage IIIB-IV NSCLC with PD-L1 tumor proportion score (TPS) ≥1% and ≥1 prior line of systemic therapy; or stage IV NSCLC with TPS ≥50%, no EGFR or ALK alteration, and no prior systemic therapy. All participants received pembrolizumab 200 mg Q3W for ≤35 cycles. The primary end point was safety. Efficacy was not formally assessed, but response data were collected as part of routine participant management. Follow-up continued until 30 days after last dose of pembrolizumab or before start of new anticancer therapy, whichever was earlier. Results: A total of 150 participants were enrolled. Among the 118 participants with melanoma, the median age was 56.0 years, 115 (97.5%) had stage IV disease, 40 (33.9%) had mucosal melanoma, 10 (8.5%) had acral lentiginous melanoma, and 89 (75.4%) were previously untreated. Among the 32 participants with NSCLC, the median age was 64.5 years, 28 (87.5%) had stage IV disease, and 26 (81.3%) had received prior treatment (1 prior line, n = 10 [31.3%]; 2 prior lines, n = 10 [31.3%]; ≥3 lines, n = 6 [18.8%]). As of the database cutoff (Aug 21, 2024), median study follow-up was 4.2 months (range, 0.7-28.2); 106 participants (89.8%) with melanoma and 28 participants (87.5%) with NSCLC had discontinued treatment, most commonly due to progressive disease (n = 82 [69.5%] and n = 16 [50.0%], respectively). Any cause adverse events (AEs) occurred in 131 participants (87.3%); grade 3-5 AEs occurred in 38 (25.3%). Treatment-related AEs occurred in 61 participants (40.7%); grade 3-5 treatment-related AEs occurred in 11 (7.3%). Four treatment-related deaths occurred (hepatic failure, pneumonitis, ischemic stroke, and cardiac tamponade). Immune-mediated AEs occurred in 33 participants (22.0%), of which the most common (≥5%) was hypothyroidism (17.3%). Grade 3-5 immune-mediated AEs occurred in 5 participants (3.3%). The objective response rate per RECIST v1.1 by investigator review was 11.0% (95% CI, 6.0-18.1; 13 partial response) in participants with melanoma and 12.5% (95% CI, 3.5-29.0; 4 partial response) in participants with NSCLC. Conclusions: The safety profile of pembrolizumab in participants from India with advanced melanoma or NSCLC was no different from what has been reported in global studies. Antitumor activity was observed in the exploratory analysis of efficacy. Clinical trial information: NCT03715205 .