Introduction IPROC is a platform trial testing novel immunotherapies in PltnR-HGSC. We report sub-studies A and B, testing durvalumab + BA3011 or BA3021 which are conditionally active humanized monoclonal antibodies (IgG1) conjugated to monomethyl auristatin E targeting AXL (BA3011) and ROR2 (BA3021) in AXL+ or ROR2+ HGSC respectively. AXL and ROR are linked to immunotherapy resistance.

Methods Eligible patients (pts) had ≤1 prior line of chemotherapy for PltnR-HGSC, ECOG 0/1, and archival tumors AXL+ (sub-study A) or ROR2+ (sub-study B) received durvalumab Q4W 1500 mg + Q2W 1.8mg/kg BA3011 or BA3021. Primary endpoint was RECIST1.1 response rate (ORR). Secondary endpoints: iRECIST ORR, RECIST/iRECIST PFS, OS and safety. Serial blood and tumor samples were collected. Sub-studies had a Simon 2-stage design with 10 pts enrolled per stage.

Results Pts screened/AXL+/ROR2+ were 62/19/41. 20 pts, 10/sub-study, were treated. Sub-study A: Best response was SD (N=7/10pts) median duration and range (MD/R) 3.6 mo/2.4 – 3.7. 6pts had G3 related AE: infusion reaction to BA3011 (N=1) and thromboembolus (N=2). G3/4 laboratory AEs included: neutropenia (N=4); lymphopenia (N=3), elevated creatinine (N=1), ALT (N=1), AST (N=1). Sub-study B: Best response, SD (N=2/9pts; duration 3.6 and 5.3 mo). 1 pt had G3 related fatigue. Grade 3 laboratory AEs included: neutropenia (N=1) and elevated ALT (N=1).

Conclusion/Implications Responses durvalumab + BA3011 (AXL) and durvalumab + BA3021 (ROR2) at these doses/schedules were not sufficient to proceed to stage 2. No new safety signals were identified. Whole exome sequencing and immune profiling of tumor and blood samples are ongoing.