Neoadjuvant therapy with mFOLFOXIRI combined with camrelizumab and bevacizumab for microsatellite stable, locally advanced rectal cancer: A single-arm, open-label phase II study.

e15633 Background: Patients with microsatellite stable (MSS) rectal cancer account for a high proportion with poor response to immunotherapy. The purpose of this study is to investigate the efficacy and safety of the neoadjuvant therapy with mFOLFOXIRI plus camrelizumab (PD-1 antibody) and bevacizumab for MSS locally advanced rectal cancer (LARC) and to explore its possible mechanisms. Methods: neoFOLCAB was a prospective, single-arm, open-label, phase 2 study done at Peking University Shougang Hospital. The trial recruited 32 patients with MSS-LARC aged between 18 and 70 years old. The enrolled patients received intravenous administration of carfilzomib, bevacizumab, and mFOLFOXIRI for 4-6 cycles. The primary endpoint was the rate of pathological and clinical complete response (cCR). Tumor tissues were subjected to NGS. Peripheral blood was collected for circulating tumor DNA (ctDNA) detection. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2100054182). The submission was approved by the Data and Safety Monitoring Committee of Peking University Shougang Hospital. Results: Between February 24, 2022, and August 9, 2024, 32 patients were enrolled, with 3 patients being excluded from the final analysis due to reasons unrelated to the study. Among the patients included, 9 were female (31%) and 20 were male (69%). The median follow-up time was 17.7 months (IQR 3.9 to 32.9 months). cCR was achieved in 10 patients (34.5%; 95% CI 16% to 53%), with 7 of them adopting the watch and wait strategy. Surgical treatment was performed in 58.6% of the patients (17 cases), and 6 patients (35.3%; 95% CI 12% to 68%) achieved pathological complete response (pCR). 13 cases (44.8%; 95% CI 26% to 64%) achieved complete response (CR). The incidence of grade 3 or higher adverse events (AEs) was 37.9%. The number of ctDNA mutations (P < 0.001), mutation abundance (P < 0.001), and mutation level (P < 0.001) all decreased with therapeutic response. Tumors in CR patients showed high infiltration levels of innate immune cells and adaptive immune cells after treatment. Conclusions: The combination of camrelizumab and bevacizumab with chemotherapy showed excellent efficacy as a neoadjuvant therapy for patients with MSS LARC with manageable treatment-related toxicity. The ctDNA indicators can serve as biomarkers for predicting the efficacy and prognosis of neoadjuvant therapy. Clinical trial information: ChiCTR2100054182 . Postoperative pathologic findings. Pathologic Finding Patients Surgical resection margins (R0/R1/R2) N=18 R0R1/R2 18 (100%)0 (0%) Pathologic risk group N=18 Very lowLowIntermediateHighVery high 10 (55.6%)1 (5.6%)0 (0%)0 (0%)7 (38.8%) pTRG Grade N=18 0123 6 (33.3%)3 (16.7%)6 (33.3%)3 (16.7%) Pathologic T stage, n (%) N=18 T0TisT1T2T3T4 6 (33.2%)1 (5.6%)0 (0%)5 (27.8%)5 (27.8%)1 (5.6%) Pathologic N stage, n (%) N=18 N0N1N2 13 (72.2%)3 (16.7%)2 (11.1%)