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 downstream 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 infusion 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 pretreated patients with ccRCC. The trial was discontinued early due to the sponsor's internal decision.

Clinicaltrials.gov Identifier: NCT04300140.