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).
Year: 2025
Type: conference-abstract
Abstract: 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 .
Source: Journal of Clinical Oncology
Institutions: CHA University Bundang Medical Center, CHA University, Samsung Medical Center, Sungkyunkwan University, Yonsei University, Yonsei Cancer Hospital, Asan Medical Center, University of Ulsan, University of Southern California, USC Norris Comprehensive Cancer Center, Seoul National University, Seoul National University Hospital, Norton Healthcare, Qurient (South Korea)
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410805213