1889P Phase Ib/II study of batiraxcept (BT, AVB-S6-500, an AXL pathway inhibitor) in combination with cabozantinib (cabo) in patients with advanced clear cell renal cell carcinoma (ccRCC) who failed first-line (1L) therapy

BT is a recombinant fusion protein containing an extracellular region of AXL combined with human immunoglobulin G1 heavy chain (Fc), demonstrating potent and specific AXL inhibition through competitive binding of its ligand GAS6. In a prior phase (P)1 study, BT RP2D was identified as 15 mg/kg IV every 2 weeks (q2w) in combination with cabo 60 mg oral daily (QD). P1b and P2 data was analyzed for BT 15 mg/kg (n=41), 20 mg/kg (n=10), q2w + cabo 60 mg QD in advanced ccRCC pts who received at least 1 prior systemic therapy. Primary endpoint was investigator-assessed objective response rate (ORR) by RECIST v1.1; key secondary endpoints were safety, progression free survival (PFS), and overall survival. As of April 21, 2023, 51 pts received at least one dose of BT with cabo with median (m) follow-up of 11.4 months (mo) (range 3.7-23.7). All pts had received prior immune-oncology therapy (IO). 51% of pts had prior VEGF-tyrosine kinase inhibitor (TKI). The ORR for the entire cohort and prior-VEGF-TKI pts was 43.1% and 53.8%, receptively. The mPFS for the entire cohort and prior-VEFG-TKI pts was 9.2 and 11.4 mo, respectively. Table presents results. Table: 1889PBatiraxcept + Cabo N=51 (%)Prior VEGF-TKIYes N=26 (%)No N=25 (%)Median age (range)62 (40-81)61 (40-76)62 (42-81)Sex (male)36 (71)18 (69)18 (72)IMDC Intermediate/poor risk40 (79)20 (77)20 (80)1, 2, 3+ Prior lines of therapy27 (53), 12 (24), 12 (24)6 (23), 8 (31), 12 (46)21 (84), 4 (16), 0ORR (CR + PR), n [95% CI]22 (43.1) [29.3, 57.8]14 (53.8) [33.4, 73.4]8 (32.0) [14.9, 53.5]mPFS mo [95% CI] Censor (n), Events (n)9.2 [7.29, 11.4] 21, 3011.4 [7.16, 16.76] 12, 149.2 [6.44, 9.33] 9, 16BT related AEs, n*43 (84)23 (89)20 (80)Grade ≥ 3 BT related AEs, n13 (26)8 (31)5 (20)*BT related AE in ≥ 20%: diarrhea (31%), fatigue (31%), and infusion-related reactions (IRR) (24%) with 10% discontinuing BT. Cabo dose reduced in 45% and discontinued in 16% pts. Open table in a new tab *BT related AE in ≥ 20%: diarrhea (31%), fatigue (31%), and infusion-related reactions (IRR) (24%) with 10% discontinuing BT. Cabo dose reduced in 45% and discontinued in 16% pts. BT + cabo demonstrated acceptable tolerability and promising efficacy in treatment-refractory ccRCC pts. BT + cabo will be further studied in a P3 trial of 2L+ ccRCC patients whose disease has progressed following IO and VEGF-TKI therapies.