645 A phase 1B/2, open-label study of Q702 in combination with intravenous pembrolizumab in patients with selected advanced solid tumors

Background

Q702 is a novel Axl/Mer/CSF1R inhibitor, able to modulate the tumor-associated macrophage (TAM) and myeloid-derived suppressor cell (MDSC) populations leading to CD8⁺ T cell activation and an increased antigen presentation of the tumor cells in syngeneic animal models. Q702 demonstrates additive effects with anti-PD-1 treatment, particularly in high myeloid containing tumor models through stimulation of innate immune components of the tumor microenvironment and elevated antigen presentation of cancer cells, which are considered the main obstacles for T cell activation by PD-1 or PD-L1 related immune checkpoint inhibitors. This data indicates that Q702 and pembrolizumab combination therapy may be a potential treatment option to enhance the activity of anti-PD-1/PD-L1 treatment. The ongoing Q702 monotherapy phase 1 study (NCT04648254) has established 100 mg as a safe starting dose for the pembrolizumab combination study. The Part 2 Dose (P2D) for the combination therapy will be determined once the recommended phase 2 dose (RP2D) for Q702 monotherapy study is established.

Methods

‘A Phase 1B/2, Open-label Study of Q702 in combination with intravenous Pembrolizumab in Patients with Selected Advanced Solid Tumors (NCT05438420)’ is currently enrolling patients in the US and Korea. This study is to determine safety and preliminary efficacy of Q702 in combination with pembrolizumab in approximately 142 subjects with advanced esophageal, gastric/GEJ, hepatocellular and cervical cancers whose disease progressed within 12 weeks of last anti-PD-1/PD-L1 dose. The study consists of 2 parts: combination therapy dose escalation and dose expansion. The Part 1 dose escalation portion will be guided by a modified Toxicity Probability Interval (mTPI) design¹ to determine the Part 2 Dose (P2D) of Q702 in combination with pembrolizumab. The Part 2 dose expansion in select tumor types will follow, utilizing an independently applied Simon’s 2 stage design for each cohort. Each enrolled patient will receive Q702 (week on/off dosing regimen) orally in combination with pembrolizumab (200 mg Q3W) intravenously in 42-day cycles. The primary endpoints are safety (DLTs and AEs) and objective response rate (ORR) per RECIST v1.1 and to determine the Part 2 dose (P2D). The secondary endpoints include assessing duration of response (DOR), progression free survival (PFS), overall survival (OS) and additional safety. The study was opened in January 2023 and is currently enrolling patients.

Trial Registration

NCT05438420

Reference

1. Ji, Yuan, Wang, Sue-Jane. Modified Toxicity Probability Interval Design: A safer and more reliable method than the 3+3 design for practical phase 1 trials. Journal of Clinical Onc, 2013;1–12.

Ethics Approval

This study has been approved by the Institutional Review Board at each investigational site in Korea and central IRB Advarra in US: Samsung Medical Center SMC-07–104-001; Seoul National University Hospital H-2209–098-1360; Severance Hospital, Yonsei University 4–2022-0952; Asan Medical Center 2023–0077; CHA Bundang Medical Center CHAMC 2022–09-049; CIRB Advarra (Norton Cancer Institute, University of Southern California Norris Comprehensive Cancer Center) MOD01522061.

Consent

All patients gave informed consent before participating in this clinical study.