Abstract CT148: Phase 1 study of the anti-immunoglobulin-like transcript 4 (ILT4) monoclonal antibody MK-4830 plus pembrolizumab plus chemotherapy in patients with advanced solid tumors

Abstract Background: In the dose escalation phase of a first-in-human phase 1 study (NCT03564691), the anti-ILT4 monoclonal antibody MK-4830 plus pembrolizumab (pembro) had a manageable safety profile and showed promising antitumor activity in participants (pts) with advanced solid tumors. Safety and efficacy for MK-4830 plus pembro plus chemotherapy (chemo) for select cohorts from the expansion phase are presented. Methods: Enrolled pts were aged ≥18 y with high-grade epithelial ovarian cancer and 1-2 prior lines of systemic therapy including ≥1 platinum-based therapy (cohort J); locally recurrent inoperable or metastatic triple-negative breast cancer naive to chemo (cohort K); or previously untreated recurrent advanced mesothelioma (cohort L). All pts received MK-4830 800 mg plus pembro 200 mg IV Q3W for 35 cycles plus chemo (cohort J: paclitaxel 80 mg/m2 [days 1, 8, and 15 Q3W] or docetaxel 75 mg/m2 Q3W or 25 mg/m2 weekly; cohort K: paclitaxel 90 mg/m2 [days 1, 8, and 15 Q4W]; cohort L: pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 Q3W for 6 cycles or carboplatin AUC 5-6 Q3W for 4 cycles). Primary end points included safety and ORR per RECIST v1.1 (cohorts J and K) or modified RECIST (mRECIST; cohort L) by investigator assessment. Exploratory end points included DOR and PFS per RECIST v1.1 (cohorts J and K) or mRECIST (cohort L) by investigator assessment. Results: At data cutoff (Sept 19, 2024), the number of enrolled pts who received treatment was 41 in cohort J, 34 in cohort K, and 42 in cohort L. Median study follow-up was 21.7 mo (range, 13.8-33.0) in cohort J, 16.1 mo (12.1-23.6) in cohort K, and 23.0 mo (14.6-32.7) in cohort L. Treatment-related AEs occurred in 37 pts (90%) in cohort J, 34 pts (100%) in cohort K, and 40 pts (95%) in cohort L; grade 3-5 events occurred in 14 pts (34%), 14 pts (41%), and 19 pts (45%), respectively. Treatment-related AEs led to death in 1 pt in cohort K (lower respiratory tract infection) and 2 pts in cohort L (1 enterocolitis and 1 myopericarditis); no treatment-related deaths occurred in cohort J. Immune-mediated AEs and infusion reactions occurred in 12 pts (29%) in cohort J, 13 (38%) in cohort K, and 13 (31%) in cohort L; grade 3-5 events occurred in 2 (5%), 3 (9%), and 2 (5%) pts, respectively. ORR was 28% (95% CI, 15-44) in cohort J, 32% (17-50) in cohort K, and 38% (24-54) in cohort L; median DOR was 4.1 mo (range, 3.2-11.2), 11.1 mo (2.7-19.5+), and 14.8 mo (3.3-27.3), respectively. Median PFS was 5.0 mo (95% CI, 4.2-5.7), 5.6 mo (3.9-9.3), and 9.7 mo (7.5-13.7), respectively. Conclusions: In pts with select advanced solid tumors, the safety profile observed with MK-4830 plus pembro plus chemo was manageable and consistent with that for each individual therapy. Modest antitumor activity was observed with the addition of MK-4830 to pembro plus chemo. Investigation of other therapies in these difficult-to-treat tumor types is warranted. Citation Format: Rafal Dziadziuszko, Sofia Baka, Eytan Ben Ami, Maria Jose de Miguel Luken, Marta Gil-Martin, John Hilton, Iwona Lugowska, Ruth Perets, Leah Suttner, Douglas C. Wilson, Omobolaji O. Akala, Penelope Bradbury. Phase 1 study of the anti-immunoglobulin-like transcript 4 (ILT4) monoclonal antibody MK-4830 plus pembrolizumab plus chemotherapy in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT148.