A phase 1b/2, open-label study of selective Axl, Mer and CSF1R inhibitor adrixetinib (Q702) in combination with intravenous pembrolizumab in patients with selected advanced solid tumors: Results of a phase 1 study (QRNT-008).

2606 Background: Adrixetinib (Q702) is an orally administrated novel Axl/Mer/CSF1R tyrosine kinase inhibitor for which the primary mechanism of action of tumor regression is through immune-stimulating effects. The safety profile, pharmacokinetics (PK) and efficacy data for Q702 in combination with pembrolizumab are presented. Methods: QRNT-008 (NCT05438420) is an ongoing Phase 1b/2 multicenter, open-label, dose escalation and expansion study in patients with advanced esophageal, gastric/GEJ, hepatocellular, and cervical cancers who have progressed on prior anti-PD-1/PD-L1 treatment. The Part 1 dose escalation was guided by a mTPI design to determine the Part 2 dose of Q702 in combination with pembrolizumab. Patients received Q702 (week on/off dosing regimen) orally at 100 mg or 120 mg doses in combination with pembrolizumab (200 mg Q3W) intravenously in 42-day cycles. Results: As of the data cutoff (December 19th, 2024), 29 patients received Q702 plus pembrolizumab across 2 dose levels: 7 patients at 100 mg and 22 patients at 120 mg. The median number of prior lines of systemic therapy was 4 (range 1-7). Of the 29 patients (3 esophageal; 11 gastric; 2 GEJ; 9 hepatocellular; 4 cervical) who received Q702 across all doses, there were no treatment discontinuations due to the treatment-related AEs (TRAEs). Most common TRAEs ≥10% were AST increase (51.7%), ALT increase (41.3%), CPK increase (37.8%) and LDH increase (34.5%). One patient dosed at 120 mg experienced 1 DLT (G3 skin rash and G3 diarrhea). Adrixetinib PK analyses showed dose dependent increase of AUC 0-last and C max . Overall response assessment (RECIST 1.1) included 1 confirmed complete response (CR) in a patient with metastatic gastric cancer (GC) and 6 patients with stable disease (SD) across multiple tumor types. Among 6 SD patients, 1 GC and 1 hepatocellular cancer (HCC) patient continued treatment for ≥24 weeks. Conclusions: Preliminary data from QRNT-008 study showed that selective Axl/Mer/CSF1R inhibitor Q702 plus pembrolizumab has a manageable safety profile. The Part 2 dose of Adrixetinib is confirmed at 120 mg. Preliminary anti-tumor activity in patients previously treated with anti-PD-1 supports further development of the combination. Clinical trial information: NCT05438420 .