Abstract 510TiP
Background
CRC is an aggressive disease which accounts for a third of cancer-related death. Compared with the microsatellite instability-high phenotype, the effect of the BRAF mutation in the MSS-CRC on the prognosis seems to be more obvious. Regorafenib and furquintinib are small-molecule multikinase inhibitors that target signaling pathways implicated in tumor angiogenesis, oncogenesis and the tumor microenvironment. Camrelizumab, an anti-PD-1 monoclonal antibody, has shown preliminary results in advanced CRC. Thus, this trial was designed to investigate the efficacy and safety of camrelizumab plus fruquintinib or regorafenib in BRAF positive-mutation advanced MSS-CRC.
Trial design
This is a phase II, single-arm, prospective trial. Eligible patients are histologically or cytologically confirmed advanced CRC with metastatic disease. Patients have to be adults (18-75 years) with ECOG PS ≤1 and BRAF V600E mutated CRC that is resistant/refractory/intolerant to ≥1 prior lines of therapy. Patients could not participate if they have bone metastases with spinal cord compression. Patients are treated with camrelizumab (200mg, iv, q2w) combined with fruquintinib (4 mg/d) or regorafenib (80 mg/d) medication for 3 weeks, 1 week apart, until disease progression or intolerance toxicity occurs. For patients, blood samples at baseline, at the time of best response and after disease progression, will undergo NGS testing, which detects a panel of gene mutations, including single nucleotide variants, insertions/deletions, copy number amplifications, and gene rearrangements. The NGS testing is needed to identify better biomarkers of response to immunotherapy in CRC. The primary endpoint is progress-free survival (PFS) assessed by researcher according to RECIST v1.1. Secondary endpoints are objective response rate, disease control rate, overall survival and safety. On the basis of a threshold PFS of 3 months, targeting an expected PFS of 5 months and assuming 12 months follow-up, 80% power and a one-sided α=0.05, this design requires 37 evaluable patients to be accrued over 2 years.
Clinical trial identification
ChiCTR2100043066.
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.