CRI-CCTG-0003/IND.240 An immunotherapy platform study in platinum-resistant high grade serous ovarian cancer (IPROC): Sub-studies A and B: Durvalumab (D) + mecbotamab vedotin (BA3011) or ozuriftamab vedotin (BA3021)

Objective IPROC is an ongoing platform trial investigating novel immunotherapy combinations in platinum resistant high grade serous ovarian cancer. Here we report on the combination of durvalumab with two conditionally active biologic antibody drug conjugates linked to monomethyl auristatin E: mecbotamab vedotin (BA3011) targeting AXL and ozuriftamab vedotin (BA3021) targeting ROR2. Methods IPROC is a non-randomized phase 2 platform trial (NCT0491816) with each sub study having a Simon’s 2 stage design. Eligible patients with tumor expression of AXL (sub-study A) or ROR2 (sub-study B) received durvalumab with BA3011 (sub-study A) or BA3021 (sub-study B). The primary endpoint was objective response rate. Tumor biopsies obtained at baseline and pre-cycle 2 were analyzed using whole exome and RNA sequencing (RNA-seq). Digital cytometry (CIBERSORTx) was used to evaluate immune cell populations. Results Ten patients were treated in each sub-study. No response was observed and, following biomarker review, neither sub-study proceeded to second stage accrual. In sub-study A 7 patients had stable disease (SD), median duration 3.6 months (range 2.4 – 3.7) with 6 patients experiencing a G3 treatment related adverse event (TRAE). In sub-study B 2 patients had SD with 1 patient experiencing a G3 TRAE. CIBERSORTx analysis of RNA-seq identified diverse intra-tumoral immune cell populations with no differences in inferred immune cell frequencies between pre- and on-treatment samples. Conclusions Durvalumab combined with neither BA3011 nor BA3021 demonstrated sufficient efficacy to proceed to second stage accrual. No new safety signals were identified. We showed the feasibility of collecting and analyzing tissue in this platform study.