Abstract CT114: Phase 1 study of the anti-immunoglobulin-like transcript 4 (ILT4) monoclonal antibody MK-4830 plus pembrolizumab in patients with previously untreated advanced head and neck squamous cell carcinoma (HNSCC) or non-small cell lung cancer (NSCLC)

Abstract Background: ILT4 is an immunosuppressive receptor commonly expressed on myeloid cells. Antagonism of ILT4 may induce a proinflammatory state and stimulate antitumor T-cell response, especially with PD- (L) 1 blockade. In the dose escalation phase of a first-in-human phase 1 study (NCT03564691), the anti-ILT4 IgG4 monoclonal antibody, MK-4830, in combination with pembrolizumab (pembro) was well tolerated and demonstrated antitumor activity in advanced solid tumors. Here, we present safety, efficacy, and biomarker analyses for MK-4830 + pembro from the multi-cohort expansion phase of patients (pts) with previously untreated advanced HNSCC or NSCLC. Methods: Pts aged ≥18 y with previously untreated advanced HNSCC and PD-L1 combined positive score (CPS) ≥1 (cohort D) or NSCLC regardless of PD-L1 status (cohorts E and F) were enrolled. Pts in all cohorts received either MK-4830 800 mg (cohorts D and E) or 1600 mg (cohort F) + pembro 200 mg Q3W for ≤35 cycles. Primary end points were safety and ORR per RECIST v1. 1 by investigator assessment. Exploratory end points included DOR and PFS per RECIST v1. 1 by investigator assessment and evaluating possible biomarkers of response to MK-4830 + pembro. Results: At data cut-off (September 27, 2023), 35, 47, and 11 pts were enrolled and received treatment in cohorts D, E, and F, respectively. Median study follow-up was 34. 4 mo (range, 26. 5-42. 4) in cohort D, 35. 9 mo (22. 4-39. 8) in cohort E, and 38. 7 mo (37. 6-39. 6) in cohort F. Adverse events (AEs) occurred in 33 pts (94%) in cohort D, 43 pts (91%) in cohort E, and 10 pts (91%) in cohort F. Treatment-related AEs (TRAEs) occurred in 20 pts (57%) in cohort D, 26 pts (55%) in cohort E, and 6 pts (55%) in cohort F; grade 3-5 TRAEs occurred in 5 pts (14%), 4 pts (9%), and 1 pt (9%), respectively. One pt in cohort E and 1 pt in cohort F died due to a TRAE (pneumonitis and pneumonia, respectively). ORR was 24% (95% CI, 11-41) in cohort D, 30% (17-45) in cohort E, and 27% (6-61) in cohort F. Median DOR was 16. 4 mo (range, 2. 2+ to 24. 4+) in cohort D, 14. 8 mo (4. 2+ to 32. 9+) in cohort E, and 8. 4 mo (3. 0-21. 5) in cohort F. Median PFS was 5. 2 mo (95% CI, 2. 0-8. 0) in cohort D, 4. 3 mo (1. 8-8. 1) in cohort E, and 3. 3 (1. 2-7. 6) in cohort F. In cohort D, T-cell-inflamed gene expression profile (TcellinfGEP) and tumor mutational burden (TMB) did not enrich for response to MK-4830 + pembro. In cohorts E and F, PD-L1 tumor proportion score (TPS) and TcellinfGEP trended higher in pts with response to MK-4830 + pembro than pts with no response; TMB did not trend with response. Conclusions: In pts with advanced HNSCC or NSCLC, first-line MK-4830 + pembro had a manageable AE profile with modest antitumor activity. Consistent with what was previously observed for pembro alone, a trend was observed between PD-L1 TPS and response to MK-4830 + pembro in pts with NSCLC. Citation Format: Byoung Chul Cho, John Hilton, Cristina P. Rodriguez, Marcelo Bonomi, Lillian L. Siu, Marta Gil-Martin, Shabana Siddiqi, Nicole M. Myer, Leah Suttner, Douglas Wilson, Omobolaji Akala, Rafal Dziadziuszko. Phase 1 study of the anti-immunoglobulin-like transcript 4 (ILT4) monoclonal antibody MK-4830 plus pembrolizumab in patients with previously untreated advanced head and neck squamous cell carcinoma (HNSCC) or non-small cell lung cancer (NSCLC) 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 CT114.