A Phase II Study of GVAX Colon Vaccine with Cyclophosphamide and Pembrolizumab in Patients with Mismatch Repair–proficient (Mmr-P) Advanced Colorectal Cancer.

563 Background: Mismatch repair proficient (MMRp) colorectal cancer (CRC) is refractory to single-agent programmed cell death protein 1 (PD1) inhibitors. Cancer vaccines may prime the tumor microenvironment for anti-PD1 therapy. Colon GVAX is an allogeneic, whole-cell, GM-CSF-secreting vaccine that induces T-cell immunity against tumor-associated antigens. GVAX has previously been studied in combination with low-dose cyclophosphamide (Cy) to inhibit regulatory T cells. Methods: We conducted an open label, single-arm, phase 2 study of GVAX/Cy in combination with the PD1 inhibitor pembrolizumab in patients with MMRp CRC who had received at least two prior lines of therapy in the metastatic setting. Patients received pembrolizumab plus Cy on day 1, GVAX on day 2, of a 21 day cycle through 4 cycles, and were then continued on a maintenance regimen of pembolizumab every 3 weeks with cy/GVAX given every 12 weeks. Results: Seventeen patients were enrolled. There were no objective responses, and the disease control rate was 18% by RECIST and 29% by irRC. The median progression free survival was 2.7 months and the median overall survival was 7.0 months. Biochemical responses (≥30% decline in CEA) were observed in 7/17 (41%) of patients. Two patients (12%) had grade 3/4 adverse events that were attributed to study therapy. To test the hypothesis that the induction of a humoral response against CEA protein had resulted in the observed biochemical responses, we measured patient titers of anti-CEA antibodies. Anti-CEA antibody titers increased 13 of 13 patients (100%) with available paired pre- and on-treatment research blood samples, but the change in anti-CEA antibody titers were similar among CEA responders and non-responders. Multiplex immunohistochemistry performed on pre- and post- biopsy specimens will be reported at the conference. Conclusions: GVAX/Cy plus pembrolizumab is well tolerated in advanced MMRp CRC and resulted in CEA responses but not radiographic responses. PFS and OS compare favorably to historical controls in this small cohort. CEA responses were not observed with PD1 monotherapy in MMRp CRC, suggesting GVAX can modulate the antitumor immune response. Clinical trial information: NCT02981524.