Abstract CT253: Results from KEYNOTE-B99: Phase 2 study of first-line (1L) pembrolizumab (pembro) plus investigational agents and chemotherapy (chemo) for extensive-stage small-cell lung cancer (ES-SCLC)

Abstract Background: ES-SCLC is an aggressive cancer with substantial mortality. Current 1L treatments include anti-PD- (L) 1 + etoposide-platinum chemo (EP), but with minimal improvements in OS vs chemo. In the phase 3 KEYNOTE-604 study, pembro + EP significantly improved PFS (P = 0. 0023) but not OS vs placebo + EP; ORR was also improved (71% vs 62%). We present data from the phase 2 KEYNOTE-B99 study (NCT04924101) of 1L pembro + investigational agents (MK-4830, anti-ILT4; boserolimab, anti-CD27; or lenvatinib), and EP for ES-SCLC. Methods: In this open-label platform study, patients (pts) were aged ≥18 y with previously untreated histologically or cytologically confirmed stage IV ES-SCLC (per AJCC v8) and ECOG PS 0 or 1. Pts were randomized 1: 1: 1 to receive MK-4830 800 mg Q3W (35 cycles; arm A), boserolimab 30 mg Q6W (18 cycles; arm B), or lenvatinib 8 mg (induction) /20 mg (maintenance) QD (arm C). All pts received pembro 200 mg Q3W (35 cycles) + etoposide 100 mg/m2 Q3W and cisplatin 75 mg/m2 Q3W or carboplatin AUC 5 mg/mL/min Q3W (4 cycles). Primary endpoints were ORR and PFS at 6 mo, both assessed per RECIST v1. 1 by BICR. Secondary endpoints included DOR, PFS, OS, and safety. Results: 122 pts received ≥1 dose of study treatment (arm A, 43; B, 41; C, 38). At data cutoff (Sep 15, 2023), median follow-up was 14. 1 (range, 6. 1-25. 7) mo. ORR was 65%, 71%, and 74% in arms A, B, and C, respectively; median DOR was 6. 8, 4. 7, and 7. 1 mo. 6-mo PFS rates were 45%, 38%, and 54%, respectively (Table). AEs (any cause) occurred in 98% of pts in arm A and all pts in arms B and C; most commonly neutropenia and anemia. Serious AEs occurred in 30%, 37%, and 55%; grade ≥3 AEs in 86%, 83%, and 87% of pts; and grade 5 AEs in 5%, 7%, and 21%, respectively. Conclusions: 1L ES-SCLC treatment with pembro + EP and MK-4830, boserolimab, or lenvatinib was associated with similar antitumor activity as in KEYNOTE-604 with pembro + EP. No new safety signals were identified. TABLE 1. NAND Group A MK-4830 + Pembro + EP (n = 43) Group B boserolimab + Pembro + EP (n = 41) Group C Lenvatinib + Pembro + EP (n = 38) ORR (95% CI), % 65. 1 (49. 1-79. 0) 70. 7 (54. 5-83. 9) 73. 7 (56. 9-86. 6) Median DOR (range), mo 6. 8 (2. 4-13. 9) 4. 7 (1. 4+ to 16. 4+) 7. 1 (1. 8 to 18. 4+) PFS - 6-mo PFS rate (95% CI), % 45. 2 (29. 9-59. 4) 37. 8 (22. 7-52. 7) 54. 2 (35. 8-69. 4) - Median PFS (95% CI), mo 5. 5 (4. 2-8. 3) 5. 5 (4. 0-6. 7) 7. 2 (5. 4-NR) Median OS (95% CI), mo 15. 5 (8. 3-NR) NR (13. 2-NR) 15. 8 (7. 2-NR) ‘+’, no PD at the time of last disease assessment. NR, not reached. Citation Format: Delvys Rodríguez-Abreu, Maximillian Hochmair, Byoung Chul Cho, Tibor Csőszi, Talia Shentzer Kutiel, Veronika Müller, Myung-Ju Ahn, Dariusz Kowalski, Michele Maio, Vladimir Moiseyenko, Alejandro Navarro, Jianxin Niu, Andrea S. Fung, Carolin Lips, Heng Zhou, Bin Zhao, Humberto Lara-Guerra, Nir Peled. Results from KEYNOTE-B99: Phase 2 study of first-line (1L) pembrolizumab (pembro) plus investigational agents and chemotherapy (chemo) for 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 CT253.