Phase 1b/2 study of batiraxcept alone and in combination with cabozantinib with or without nivolumab for advanced clear cell renal cell carcinoma

Background: Anexelokto (AXL) protein and its ligand, growth arrest specific-6 (GAS6), are important drivers of metastasis in patients with advanced clear cell renal cell carcinoma (ccRCC). Batiraxcept competitively binds GAS6 limiting interaction with AXL and thereby reduces down¬stream signaling. We present the safety and efficacy of batiraxcept alone and in combination with cabozantinib with or without nivolumab in patients with advanced ccRCC. Patients and methods: Phase 1b tested batiraxcept (15 and 20 mg/kg) plus cabozantinib (60 mg, N = 26) to identify the recommended phase 2 dose (RP2D) and evaluate safety. Phase 2 tested the batiraxcept RP2D as monotherapy (N = 10), as doublet therapy with cabozantinib (60 mg, N = 25) in previously treated patients, and as triplet therapy with cabozantinib (40 mg) and nivolumab (240 or 480 mg) in treatment-naïve patients (N = 11), with objective response rate (ORR) as the primary endpoint. Results: During the phase 1b (N = 26) study portion, no dose-limiting treatment-related adverse events (trAEs) were noted and batiraxcept 15 mg/kg plus cabozantinib 60mg was selected as the RP2D. The ORR across all doublet patients (phase 1 and 2, n = 51) was 43%, with median PFS of 9.2 months and grade ³3 trAEs in 73% of patients. Common batiraxcept trAEs were diarrhea (31%), fatigue (31%), and infu¬sion reactions (24%). No new safety signals were noted among the triplet or monotherapy arms, which demonstrated 54% and 0% ORR, respectively. Conclusion: Batiraxcept was well tolerated with promising early efficacy signal when combined with cabozantinib, especially in heavily pre¬treated patients with ccRCC. The trial was discontinued early due to the sponsor's internal decision.