Immunotherapy has limited efficacy in metastatic colorectal cancer (mCRC). Understanding mechanisms mediating immune resistance in microsatellite stable (MSS) colorectal tumors remains an ongoing challenge. Novel combination immunotherapy-based approaches have been developed under the rationale of overcoming immune resistance and developing effective immune response against colorectal tumor cells. Preclinical studies have demonstrated that cetuximab may modulate immune response to cancer cells. In this scenario, the inhibition of PD-L1 with IgG1 MAb avelumab in combination with anti-EGFR IgG1 monoclonal antibody cetuximab could be a strategy for potentiating antitumor activity. The CAVE phase II single-arm clinical trial provided the first evidence of clinical activity of combining cetuximab plus avelumab in 77 patients with RAS wild-type (WT) mCRC. This combination had a good toxicity profile, with a low rate of common grade 3 adverse events.

CAVE-2 (Cetuximab-AVElumab) mCRC: A Phase II Randomized Clinical Study of the Combination of Avelumab Plus Cetuximab as a Rechallenge Strategy in Pre-Treated RAS/BRAF Wild-Type mCRC Patients

Napolitano, Stefania;Martini, Giulia;Ciardiello, Davide;Martinelli, Erika;Troiani, Teresa;Ciardiello, Fortunato
2022

Abstract

Immunotherapy has limited efficacy in metastatic colorectal cancer (mCRC). Understanding mechanisms mediating immune resistance in microsatellite stable (MSS) colorectal tumors remains an ongoing challenge. Novel combination immunotherapy-based approaches have been developed under the rationale of overcoming immune resistance and developing effective immune response against colorectal tumor cells. Preclinical studies have demonstrated that cetuximab may modulate immune response to cancer cells. In this scenario, the inhibition of PD-L1 with IgG1 MAb avelumab in combination with anti-EGFR IgG1 monoclonal antibody cetuximab could be a strategy for potentiating antitumor activity. The CAVE phase II single-arm clinical trial provided the first evidence of clinical activity of combining cetuximab plus avelumab in 77 patients with RAS wild-type (WT) mCRC. This combination had a good toxicity profile, with a low rate of common grade 3 adverse events.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11591/475471
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