Study design and statistical hypothesis
colorectal MSI disease, colorectal MSS, MSS disease, colorectal MSS disease
DISEASE, SECONDARY
This was a multicenter, single-arm, open-label, phase 1/2 study. The study was performed in two steps (Extended Data Fig. The primary objective of step 2 was to determine efficacy of the combination of durvalumab (anti-PD-L1) + tremelimumab (anti-CTLA-4) + mFOLFOX6 in terms of PFS in patients with colorectal MSS disease. The secondary objectives were:to determine efficacy of the combination of durvalumab (anti-PDL1) + tremelimumab (anti-CTLA-4) + mFOLFOX6 in terms of response to treatment and OS in patients with colorectal MSS disease.to determine efficacy of the combination of durvalumab (anti-PD-L1) + tremelimumab (anti-CTLA-4) + mFOLFOX6 in terms of PFS, response to treatment and OS in patients with colorectal MSI disease.Sample size calculation was performed using PASSV13 (NCSS statistical software), using the following null and alternative hypothesis for primary objective of step 2: H0: 50% of PFS at 3 months; H1: 70.7% PFS at 3 months (equivalent to 50% of PFS at 6 months). According to Simon’s design, with α = 10% and β = 10% (90% power), 43 patients with MSS disease are needed for the primary endpoint analysis. Accounting for 20% of non-evaluable patients, 52 patients with MSS disease will be included. Among these 52 patients, the first nine patients were used for the safety population analysis. The prevalence of MSS disease being around 90–95%, five additional patients will be included, leading to 57 patients in the overall study.