53O Results from a phase II part I trial of mecbotamab vedotin (BA3011), a CAB-AXL-ADC, in patients with advanced refractory sarcoma

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.