Abstract CT256: Results from KEYNOTE-B98: A phase 1b/2 study of pembrolizumab plus investigational agents in patients with anti-PD-(L)1-refractory extensive-stage small-cell lung cancer (ES-SCLC)

Abstract Background: Anti-PD-L1 plus chemotherapy is a recommended first-line (1L) treatment option for ES-SCLC. However, most patients (pts) relapse and effective second-line (2L) treatment options are limited. Pembrolizumab (pembro) has demonstrated antitumor activity in previously treated ES-SCLC. The KEYNOTE-B98 study (NCT04938817) evaluated pembro in combination with investigational agents as 2L therapy for anti-PD- (L) 1-refractory ES-SCLC. We present initial results from this study. Methods: This randomized, phase 1b/2, multicenter, open-label, platform study enrolled adult pts with confirmed ES-SCLC (stage IV per AJCC v8. 0) that progressed ≤12 wk of last anti-PD- (L) 1 dose given as part of 1L platinum-based therapy, measurable disease per RECIST v1. 1, and ECOG PS of 0-1. Pts were randomized 1: 1: 1: 1 to: (A) MK-1308A (coformulation of quavonlimab anti-CTLA4 25 mg + pembro 400 mg) Q6W, (B) MK-1308A Q6W + lenvatinib 20 mg QD, (C) MK-1308A Q6W + MK-4830 (anti-ILT4) 800 mg Q3W, and (D) MK-4280A (coformulation of favezelimab anti-LAG3 800 mg + pembro 200 mg) Q3W. A safety lead-in was performed for the first 21 days of treatment in cohort C in ≤10 pts evaluable for dose-limiting toxicities (DLTs), followed by efficacy evaluation. Pts in safety lead-in were not randomized. Primary endpoints were safety (DLTs in safety lead-in phase, AEs, and discontinuations due to AEs) and ORR per RECIST v1. 1 by BICR. Secondary endpoints were PFS and DOR per RECIST v1. 1 by BICR. Results: 76 pts received ≥1 dose of study treatment: cohort A, n = 19; B, n = 20; C, n = 17; D, n = 20. Median follow-up at data cutoff (Jul 3, 2023) was 12. 9 (range, 5. 9-21. 8) mo. During safety lead-in, 1 pt had a DLT of grade 3 arthralgia. Treatment-related AEs (TRAEs) occurred in 12 pts (63%; grade 3/4, n = 2, 11%) in cohort A, 17 (85%; grade 3/4, n = 6, 30%) in cohort B, 12 (71%; grade 3/4, n = 1, 6%) in cohort C, and 15 (75%; grade 3/4, n = 4, 20%) in cohort D; none were grade 5. 1 pt (5%) in cohort A, 3 (15%) in cohort B, 0 in cohort C, and 2 (10%) in cohort D had TRAEs that led to treatment discontinuation. Confirmed ORR (95% CI) was 5% (0%-26%; 1 PR) in cohort A, 25% (9%-49%; 5 PR) in cohort B, 0% (0%-20%) in cohort C, and 0% (0%-17%) in cohort D. Median (range) DOR was not reached (9. 4+ to 9. 4+ mo) in group A and 3. 9 (2. 0-3. 9) mo in group B. Median (95% CI) PFS was 1. 4 (1. 2-2. 6) mo, 3. 9 (1. 7-5. 3) mo, 1. 2 (0. 8-1. 4) mo, and 2. 6 (1. 4-4. 0) mo in cohorts A-D, respectively. Conclusions: In the KEYNOTE-B98 study of anti-PD- (L) 1-refractory ES-SCLC, no new safety signals were identified for the pembro-based combinations investigated. Modest antitumor activity was observed with MK-1308A ± lenvatinib, but no activity for MK-1308A + MK-4830 or for MK-4280A. This study provided proof-of-concept for the feasibility of platform trials in 2L ES-SCLC. Further investigation of new compounds and combinations is needed in this population. Citation Format: Alejandro Navarro, Myung-Ju Ahn, James Stevenson, Nir Peled, Talia Shentzer Kutiel, Florian Huemer, Dong-Wan Kim, Maria Jove Casulleras, Adnan Khattak, Dariusz Kowalski, Natasha B. Leighl, Filippo de Marinis, Carolin Lips, Jiaxin Niu, Mo Huang, Bin Zhao, Hazem El-Osta, Taofeek Owonikoko. Results from KEYNOTE-B98: A phase 1b/2 study of pembrolizumab plus investigational agents in patients with anti-PD- (L) 1-refractory extensive-stage small-cell lung cancer (ES-SCLC) abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT256.