640P A phase II, multicenter, open-label study of PolyPEPI1018 in combination with atezolizumab in participants with relapsed or refractory microsatellite-stable metastatic colorectal (MSS mCRC) cancer (Oberto-301): Initial results

The efficacy of checkpoint inhibitor immunotherapy in MSI-H mCRC has not been replicated in MSS mCRC. Therefore, additional interventions are needed to convert immunologically “cold” MSS CRC to “hot” tumors resembling MSI-H tumors. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine containing 12 immunogenic epitopes derived from 7 cancer testis antigens which demonstrated early evidence of clinical activity, in first-line MSS mCRC. Patients with MSS mCRC who have progressed on 2-3 lines of prior chemotherapy regimen received PolyPEPI1018 (1.2 mg, sc) and atezolizumab (1,200 mg, iv) Q3W. The primary endpoint was safety. A Simon 2-stage design was applied; data from the stage 1 of the study will be presented. 18 patients (77% female) were enrolled for stage 1 of the study. At baseline, median age was 55 years (range 38–79), 50% had liver metastases and 61% received at least 3 lines of prior therapies. PD-L1 expression was <1% for 85% of patients. The median number of doses received was 4 (range 2-10). A formal review of safety was performed after the initial 6 participants received 2 cycles of study therapy. The combination was well-tolerated; most common side effect related to treatment was Grade (Gr) 1-2 local skin reaction (n=12). Gr 3 events (n=2) at least possibly related to treatment were nausea and vomiting. There were no Gr 4-5 events or study discontinuation due to treatment AE. The ORR was 0% and the DCR was 68% (n=18). Post-treatment, vaccine-specific T cell responses were detected in the PBMC of 3/4 subjects tested and 3/5 patients had increased density of CD3+ and CD8+ TILs by up to 10-fold. The average PD-L1 expression (IC %) increased significantly after treatment (n=5; p=0.04), consequently 2/5 patients’ tumor converted to high Immunoscore (Veracyte). PolyPEPI1018 in combination with atezolizumab has a manageable safety profile. PolyPEPI1018 induced immunological responses at both peripheral and tumor level, converted “cold” tumor into “hot”, although to date no responses per RECIST have been noted. The study is on-going.