Abstract CT099: NGM707 in combination with pembrolizumab in advanced or metastatic solid tumors: Preliminary results from dose escalation

Abstract BACKGROUND: NGM707-IO-101 (NCT04913337) is a Phase 1/2, dose escalation/expansion study evaluating NGM707, a humanized monoclonal antibody that blocks ILT2 and ILT4 receptors, as monotherapy or in combination with pembrolizumab. Here we report data from the combination part of the study. METHODS: Eligible patients (pts) with advanced/metastatic solid tumors were enrolled into escalating dose cohorts of 200-1800 mg NGM707 combined with 200 mg pembrolizumab, administered Q3W iv. Assessment of safety and tolerability and recommended expansion doses for NGM707 in combination with pembrolizumab were the primary objectives of the study. Secondary and exploratory objectives included assessment of pharmacokinetics/receptor occupancy (RO), immunogenicity, biomarkers, and preliminary antitumor activity per RECIST v1. 1. RESULTS: As of 06 Nov 2023, 46 pts have been enrolled in the combination escalation at dose levels up to 1800 mg; 5 pts crossed over from monotherapy. Median age 58. 5 yrs 28-81; ECOG PS 0 (19. 6%), 1 (80. 4%). Pts had received a median of 3 prior therapies (range 1-6) and all pts had metastatic disease. Overall, 20/45 pts had prior exposure to anti-PD1/anti-PD-L1. Treatment-related adverse events (any grade/grade ≥3) occurred in 41. 3%/4. 4% of pts. The most common treatment-related adverse events were fatigue (17. 4%), diarrhea (6. 5%), myalgia (4. 3%), arthralgia (4. 3%), and nausea (4. 3%). No dose-limiting toxicities were observed. A maximum tolerated dose was not reached, and the maximum administered dose was 1800 mg NGM707 in combination with 200 mg pembrolizumab. Peripheral immune cells showed dose-dependent RO, with doses ≥ 200 mg maintaining ILT2 and ILT4 RO for the entire dosing interval. PK of NGM707 was typical for monoclonal antibodies, with a half-life of 12. 8 days. Gene expression changes associated with myeloid cell and T cell activation were observed in tumor biopsies post-treatment. Of 37 response-evaluable pts, best overall responses to date are PR (confirmed) in 4 pts, SD in 12 pts, representing a DCR of ~43%. Nine pts had reduced target lesion (TL) size with a maximum reduction of 100%. Out of the 4 patients who had PR, 3 patients were pre-treated with anti-PD1/anti-PD-L1. Two subjects with MSS CRC achieved confirmed PR, one of them with TL reduction that allowed subsequent surgical resection of all gross residual disease and confirmed pathological CR with no active tumor cells and ctDNA below detection. CONCLUSIONS: NGM707 in combination with pembrolizumab appears to be safe and well tolerated at all dose levels. In this advanced and metastatic solid tumor cohort, early efficacy signals have been observed. Preliminary evidence of myeloid cell reprogramming was observed in paired tumor biopsies. Trial enrollment for the expansion part of the study is ongoing and updated data will be presented in the future. Citation Format: Judy S. Wang, Manish R. Sharma, William J. Edenfield, Kartik Sehgal, Do-Youn Oh, Yixing Jiang, Joel Michalski, Jeeyun Lee, Hans Hammers, Li-Yuan Bai, Chih-Hung Hsu, Brenda Dampier, Kefei Zhou, Li Yan, Lisa K. Blum, Joanne Sloan-Lancaster, Daniel D. Kaplan, Dhiraj Abhyankar, Hsiao D. Lieu, Vladimir Hanes, Aung Naing. NGM707 in combination with pembrolizumab in advanced or metastatic solid tumors: Preliminary results from dose escalation 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 CT099.