Pembrolizumab with Capox Bevacizumab in patients with microsatellite stable metastatic colorectal cancer and a high immune infiltrate: The FFCD 1703-POCHI trial

• DOI: 10.1016/j.dld.2021.06.009
• Publication Date: 2021-06-30T07:36:38Z
• Authors: Claire Gallois; Jean-François Emile; Stefano Kim; Carole Monterymard; Marine Gilabert; Jérémie Bez; Astrid Lièvre; Laetitia Dahan; Pierre Laurent-Puig; Laurent Mineur; Romain Coriat; Jean-Louis Legoux; Vincent Hautefeuille; Jean-Marc Phelip; Thierry Lecomte; Harry Sokol; Claude Capron; Violaine Randrian; Come Lepage; Nicolas Lomenie; Camille Kurtz; Julien Taieb; David Tougeron
• Keywords: Tumour-infiltrating lymphocytes; [SDV.CAN]Life Sciences [q-bio]/Cancer; [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology; Antibodies, Monoclonal, Humanized; Colorectal cancer; DNA Mismatch Repair; [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology; 3. Good health; Clinical trial; Bevacizumab; 03 medical and health sciences; Antineoplastic Agents, Immunological; Clinical Trials, Phase II as Topic; 0302 clinical medicine; [SDV.CAN] Life Sciences [q-bio]/Cancer; Checkpoint blockade; Antineoplastic Combined Chemotherapy Protocols; Humans; Microsatellite Instability; Colorectal Neoplasms; Immune Checkpoint Inhibitors

Pembrolizumab, a PD1 immune checkpoint inhibitor (ICI), was recently reported to be very effective in patients with microsatellite instable/deficient mismatch repair metastatic colorectal cancer (MSI/dMMR mCRC), unlike patients with microsatellite stable/proficient MMR (MSS/pMMR) mCRC, in whom ICIs are generally ineffective. However, about 15% of MSS/pMMR CRCs are highly infiltrated by tumour infiltrating lymphocytes. In addition, both oxaliplatin and bevacizumab have been shown to have immunomodulatory properties that may increase the efficacy of an ICI. We formulated the hypothesis that patients with MSS/pMMR mCRC with a high immune infiltrate can be sensitive to ICI plus oxalipatin and bevacizumab-based chemotherapy. POCHI is a multicenter, open-label, single-arm phase II trial to evaluate efficacy of Pembrolizumab with Capox Bevacizumab as first-line treatment of MSS/pMMR mCRC with a high immune infiltrate for which we plan to enrol 55 patients. Primary endpoint is progression-free survival (PFS) at 10 months, which is expected greater than 50%, but a 70% rate is hoped for. Main secondary objectives are overall survival, secondary resection rate and depth of response. Patients must have been resected of their primary tumour so as to evaluate two different immune scores (Immunoscore® and TuLIS) and are eligible if one score is "high". The first patient was included on April 20, 2021.