Abstract CT072: First in human trial of Q702 in patients with advanced solid tumors

Abstract Background: Q702 is an orally administrated novel Axl/Mer/CSF1R tyrosine kinase inhibitor for which the primary MOA of tumor regression is through immune-stimulating effects. Methods: This is a first-in-human, multicenter, dose escalation and expansion study of Q702 in patients with advanced solid tumors (NCT04648254). Primary objective is to determine the MTD, DLTs, safety profile and RP2D of Q702. Secondary objectives include PK and PD profiles of Q702. Dose escalation cohorts from 4 to 240 mg (7 days on, 7 days off dosing schedule) followed an adaptive 3+3 design. An expansion was initiated at the RP2D. Results: As of 11/6/24 a total 51 patients (40 in dose escalation and 11 in dose expansion phase) were enrolled which included 27 male and 24 female patients with median age of 63 years (32-82) with a median of 5 prior lines of treatment (1-9). Treatment related AEs (TRAEs) in ≥10% of patients included fatigue, dysgeusia, AST/ALT increased, nausea and CPK increased. Grade 3 TRAEs included AST/ALT/CPK increased. These isolated laboratory abnormalities were reported more frequently at the higher dose levels. No grade 4 or 5 TRAEs were reported. There was one DLT of G3 AST/ALT at 180 mg. MTD was not reached. The 120 mg dose was determined as RP2D based on the overall safety and PK. Mild neurological events were noted at doses above 120 mg including Grade 2 somnolence and dysgeusia. Of 46 response evaluable patients, 12 achieved stable disease with 6 patients (1 in 14 mg, 4 in 120 mg and 1 in 240 mg) manifesting progression free survival exceeding 16 weeks despite heavily pretreated. Systemic exposure was dose dependent for Q702 and its major metabolites. No dose dependent changes in sAxl were observed due to target saturation at doses ≥ 30 mg, which is comparable to the efficacy dose level observed in animal models. Plasma mCSF levels increased with increasing dose levels. Non-classical monocyte depletion, a functional biomarker associated with CSF1R inhibition, followed a dose-dependent pattern and was completely depleted at the 120 mg dose level. Based on the PK-PD model prediction, CSF1R inhibition activity was deemed significant for doses ≥ 30 mg. Conclusions: Q702 is a novel Axl/Mer/CSF1R inhibitor with a manageable monotherapy safety profile and pharmacodynamic evidence of Axl and CSF1R inhibition. The neurological events are associated with reversible depletion of microglial cells (Barca et al. 2021), the asymptomatic AST/ALT/CPK increases are felt to be associated with the Kupffer cell reduction. Both of these reversible AEs are attributed to CSF1R inhibition. The majority of TRAEs were mild to moderate. The RP2D is 120 mg. Single agent activity was modest in this group of unselected and heavily pre-treated patients. Q702 as single agent and combination therapies are warranted and under investigation. Citation Format: Devalingam Mahalingam, Angela Alistar, Andrew Hendifar, Jinho Choi, Kiyean Nam, Anthony El-Khoueiry. First in human trial of Q702 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 CT072.