GAS6/AXL-Blocking Batiraxcept + Cabozantinib Yields 43% ORR in Heavily Pretreated ccRCC

Batiraxcept—a recombinant Fc fusion that soaks up GAS6 to shut down AXL signaling—was paired with cabozantinib in the phase 1b/2 NCT04300140 study. Among 51 previously treated clear-cell RCC patients given the doublet, investigator-assessed ORR hit 43% and median PFS reached 9.2 mo; grade ≥3 treatment-related AEs appeared in 73% (diarrhea 8%, fatigue 6%, hypertension 6%). A small first-line triplet cohort (batiraxcept + cabozantinib + nivolumab, n = 11) showed 54% ORR, while batiraxcept monotherapy (n = 10) produced none. For comparison, post-TKI cabozantinib alone delivers ~21% ORR and 7.4 mo PFS, and the approved first-line nivo + cabo combo posts 56% ORR and 16.6 mo PFS. The study was terminated early for business reasons, so OS and durability remain unclear.