53O Results from a phase II part I trial of mecbotamab vedotin (BA3011), a CAB-AXL-ADC, in patients with advanced refractory sarcoma
S. Pollack, A.P. Conley, William D. Tap, Yen Cc, John A. Charlson, Lara E. Davis, A. Chalmers, Mihaela Druta, Elizabeth T. Loggers, Jaspreet Singh Grewal, Gerald S. Falchook, Brian Schulte, Thomas Yau, Angela Kim, Herbert H. Loong, Sophia George, Bhuvana A. Setty, Leo Mascarenhas, Gregory M. Coté, B. Wilky
Abstract
AXL is a cell-surface receptor tyrosine kinase highly expressed in several sarcoma subtypes that has been associated with tumor resistance to chemotherapy. Mecbotamab vedotin (BA3011) is a conditionally active biologic anti-AXL antibody-drug conjugate (CAB-AXL-ADC) that conditionally and reversibly binds AXL under tumor-specific, low-pH conditions, which reduces off-tumor toxicity and immunogenicity, avoids tissue-mediated drug deposition, and improves pharmacokinetics. This phase 2 part 1 open-label study evaluated BA3011 in adult and adolescent patients (pts) with AXL-expressing (tumor membrane percent score ≥50%) advanced refractory sarcoma who received either BA3011 monotherapy 1.8 mg/kg every 2 weeks (Q2W) or BA3011 1.8 mg/kg Q2W + nivolumab. Efficacy endpoints were disease control rate (DCR; objective response or stable disease for ≥12 weeks), number of responders (complete or partial), and progression-free survival (PFS) rate at week 12, while safety was assessed via treatment-emergent adverse events (TEAEs). Eighty-seven pts received BA3011 monotherapy and 26 received BA3011 + nivolumab. The median (range) duration of BA3011 treatment was 56.0 (11-315) and 56.5 (9-476) days in the monotherapy and combination therapy cohorts, respectively. The most common TEAEs of special interest among monotherapy pts were peripheral neuropathy (32.2%), neutropenia (25.3%), and abnormal liver function tests (20.7%). Grade 3+ TEAEs occurring in ≥5% of monotherapy pts included neutropenia (18.4%), decreased lymphocyte count (9.2%), and abdominal pain (5.7%). BA3011, with or without nivolumab, achieved a PFS rate of 39.9% and DCR of 41.1%, and 5 pts responded (Table). Table: 53OEfficacy of BA3011 monotherapy and BA3011 + nivolumab in patients with advanced refractory sarcomaBA3011 monotherapy (n=87)*BA3011 monotherapy and BA3011 + nivolumab (n=113)*Prior lines of treatment, n (%)≤243 (49.4)59 (52.2)3+41 (47.1)51 (45.1)Missing3 (3.4)3 (2.7)PFS rate at week 12, % (95% CI)40.7 (29.9-51.3)39.9 (30.5-49.1)Response rate (CR/PR), n (%) (95% CI)3 (3.5) (0.7-9.9)5 (4.5) (1.5-10.1)DCR, n (%) (95% CI)37 (43.0) (32.4-54.2)46 (41.1) (31.9-50.8)*One patient lost to follow-up was not evaluable for response rate and DCR. Abbreviations: CR, complete response; DCR, disease control rate; PFS, progression-free survival; PR, partial response. Open table in a new tab *One patient lost to follow-up was not evaluable for response rate and DCR. Abbreviations: CR, complete response; DCR, disease control rate; PFS, progression-free survival; PR, partial response. Promising disease control with acceptable tolerability justifies further evaluation of BA3011 ± nivolumab in a randomized controlled trial among pts with heavily pretreated metastatic bone and soft tissue sarcomas.