74MO - mFOLFOX6 + bevacizumab + PD-1 monoclonal antibody in locally advanced MSS CRC (BASKETⅡ): A prospective, single-arm, open-label, phase II study

Background

The efficacy of PD-1 monoclonal antibody treatment has been poor in colorectal cancer (CRC) patients with microsatellite stable (MSS) CRC, with most data derived from stage IV patients with distant metastasis. For T4NxM0 CRC patients, achieving R0 resection is challenging, often leading to recurrence and a decrease in patient survival. This study aims to assess the efficacy and safety of mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody treatment in patients with T4NxM0 MSS CRC.

Methods

This study aims to recruit a total of 38 patients with T4NxM0 MSS CRC. Main inclusion criteria include histologically confirmed colon and upper rectum MSS adenocarcinoma. All enrolled patients receive six doses of intravenous sintilimab (200 mg/dose), mFOLFOX6 and bevacizumab (5 mg/kg for 5 doses to avoid delaying surgery) every 2 weeks. Surgery is performed 2 weeks after the final dose of chemotherapy. The primary endpoint is the pathological complete response (pCR) rate, with secondary endpoints including the incidence of immunotherapy-related adverse events (irAEs), chemotherapy-related adverse events (crAEs), R0 resection rate.

Results

Between June 2021 and May 2024, 38 (20 males and 18 females) T4NxM0 MSS CRC patients were enrolled. The median age was 57 years (22-74). Fifteen patients had right-sided colon cancer, 19 had left-sided colon cancer and 4 had upper rectal cancer. Thirty-four patients underwent surgery, 20.6% (7/34) of patients achieved pCR who were all with colon cancer, 64.7% (22/34) achieved a major pathological response (MPR). Tumor regression grades (TRG) were distributed as follows: TRG 0 (23.5%), TRG 1 (23.5%), TRG 2 (41.2%), and TRG 3 (11.8%). With a median follow-up of 14.2 (0.7-34.3) months, no recurrences were observed. The most common crAEs being grades 1-2 vomiting (42.9%) and acro-numbness (57.1%). One patient (3.0%) experienced grade 3 irAEs (hypothyroidism). The remaining 4 patients are undergoing neoadjuvant therapy.

Conclusions

Patients with T4NxM0 MSS CRC treated with mFOLFOX6 + Bevacizumab + PD-1 monoclonal antibody as first-line therapy demonstrated a promising improvement in pCR rate with acceptable side effects. Further data will be reported in subsequent analyses.

Clinical trial identification

NCT04895137.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.