CXCR2 antagonist navarixin in combination with pembrolizumab in select advanced solid tumors: a phase 2 randomized trial

• DOI: 10.1007/s10637-023-01410-2
• Publication Date: 2024-02-07T12:02:22Z
• Authors: Andrew J. Armstrong; Ravit Geva; Hyun Cheol Chung; Charlotte Lemech; Wilson H. Miller; Aaron R. Hansen; Jong-Seok Lee; Frank Tsai; Benjamin J. Solomon; Tae Min Kim; Christian Rolfo; Vincent Giranda; Yixin Ren; Fang Liu; Bhargava Kandala; Tomoko Freshwater; Judy S. Wang
• Keywords: Male; Adult; 0301 basic medicine; Lung Neoplasms; Research; 610; Antibodies, Monoclonal, Humanized; Prostatic Neoplasms, Castration-Resistant; 03 medical and health sciences; Carcinoma, Non-Small-Cell Lung; Antineoplastic Combined Chemotherapy Protocols; Humans; Immunologic Factors

Summary C-X-C motif chemokine receptor 2 (CXCR2) has a role in tumor progression, lineage plasticity, and reduction of immune checkpoint inhibitor efficacy. Preclinical evidence suggests potential benefit CXCR2 inhibition multiple solid tumors. In this phase study (NCT03473925), adults with previously treated advanced or metastatic castration-resistant prostate cancer (CRPC), microsatellite-stable colorectal (MSS CRC), non–small-cell lung (NSCLC) were randomized 1:1 to the antagonist navarixin 30 100 mg orally once daily plus pembrolizumab 200 intravenously every 3 weeks up 35 cycles. Primary endpoints investigator-assessed objective response rate (RECIST v1.1) safety. Of 105 patients (CRPC, n=40; MSS CRC, NSCLC, n=25), had partial (2 CRPC, 1 CRC) for ORRs 5%, 2.5%, 0%, respectively. Median progression-free survival was 1.8–2.4 months without dose-response relationship, closed at prespecified interim analysis lack Dose-limiting toxicities occurred 2/48 (4%) receiving 3/48 (6%) mg; events included grade 4 neutropenia transaminase elevation, hepatitis, pneumonitis. Treatment-related adverse 70/105 (67%) led treatment discontinuation 7/105 (7%). Maximal reductions from baseline absolute neutrophil count 44.5%−48.2% (cycle 1) 37.5%−44.2% 2) within 6−12 hours postdose both groups. Navarixin did not demonstrate sufficient efficacy study. Safety tolerability combination manageable. ( Trial registration : ClinicalTrials.gov , NCT03473925).