Phase II Study of Pembrolizumab Plus Capecitabine and Bevacizumab for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer.

Abstract

Background: This study evaluated the safety, tolerability and preliminary efficacy of pembrolizumab in combination with capecitabine and bevacizumab in microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

Patients and methods: Patients with MSS/pMMR mCRC with stable or progressive disease on at least 1 prior fluoropyrimidine-based therapy received capecitabine 1000 mg/m² by mouth twice daily days 1 to 14, bevacizumab 7.5 mg/kg day 1, and pembrolizumab 200 mg day 1 every 3 weeks. The primary endpoint was overall response rate by RECIST 1.1. Secondary endpoints were safety, duration of response, progression-free survival (PFS), and overall survival (OS).

Results: Forty-four patients were enrolled between April 2018 and October 2021. Median follow up time was 9.3 months, while median time on treatment was 6 months. Overall response rate for 40 evaluable patients was 5% with median duration of response of 13.5 months. Median PFS was 4.1 months, and median OS was 10.1 months. Grade ≥ 3 treatment related adverse events occurred in 13 patients (30%); none were classified as immune-related. Grade 1 to 2 immune-related adverse events occurred in 8 patients (18%). Dose modifications occurred in 27 patients (61%), most commonly for palmar-plantar erythrodysesthesia. Single cell RNA sequencing on a subset of tumor biopsies demonstrated that the frequency of dendritic cells and tumor-infiltrating activated T cells correlated with time on treatment.

Conclusions: The combination of pembrolizumab with capecitabine and bevacizumab was tolerable with an expected toxicity profile in MSS/pMMR mCRC patients. The overall response rate of 5% did not meet the prespecified target of ≥ 15%; however, 55% patients remained on treatment > 6 months.

Clinicaltrials: gov Identifier: clinicaltrials.gov: NCT03396926.