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)
Authors: Cho Byoung Chul , Hilton John , Rodriguez Cristina P. , Bonomi Marcelo , Siu Lillian L. , Gil-Martin Marta , Siddiqi Shabana , Myer Nicole M. , Suttner Leah , Wilson Douglas , Akala Omobolaji , Dziadziuszko Rafal 
Published: April 2024

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(7_Suppl):Abstract nr CT114.