119TiP - A randomized, controlled, multicenter phase III study of IBI310 (anti-CTLA-4 antibody) plus sintilimab (anti-PD-1 antibody) as neoadjuvant treatment for resectable microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colon cancer

Background

There is a significant unmet clinical need for effective neoadjuvant treatment options for colon cancer, particularly for MSI-H/dMMR tumors, as conventional neoadjuvant chemotherapy has shown limited benefit in this subgroup. PD-1 with or without CTLA-4 inhibitors have shown promising efficacy in metastatic MSI-H/dMMR colorectal cancer, but none of them has yet been approved for localized tumors in the neoadjuvant setting. Our randomized, controlled, phase Ib study has demonstrated a significantly improved pathologic complete response (pCR) rate with neoadjuvant IBI310 plus sintilimab compared to sintilimab alone in MSI-H/dMMR colon cancer (2024 ASCO Annual Meeting, abstract 3505).

Trial design

Here, we present the phase III study (Neoshot), which is ongoing in China to evaluate IBI310 plus sintilimab as neoadjuvant treatment, compared with radical surgery alone for stage IIb-III MSI-H/dMMR colon cancer. A total of 350 patients (pts) will be enrolled and randomized in 1:1 ratio to the experimental and control groups. Stratification factors include baseline imaging risk assessment (high risk: T4 or N2 vs. low risk: T1-3 and N1) and tumor location (left-sided vs. right-sided). The main inclusion criteria are: 1) age ≥18 years; 2) previously untreated colon adenocarcinoma; 3) stage IIb-III (cT4 or cN+ [AJCC 8^th edition]); 4) eligible for R0 resection; 5) MSI-H or dMMR; 6) ECOG PS 0 or 1. In the experimental group, pts receive neoadjuvant treatment with IBI310 1 mg/kg plus sintilimab 200 mg in cycle 1 and sintilimab 200 mg in cycle 2, followed by radical surgery within 36-56 days after the first dose. In the control group, pts undergo radical surgery without neoadjuvant therapy. Use of adjuvant chemotherapy with oxaliplatin plus capecitabine is at the investigator’s discretion according to postoperative pathological evaluation and clinical guidelines. The primary endpoints are pCR rate of the experimental group and event-free survival. The secondary endpoints are R0 resection rate, overall survival, safety, pharmacokinetics and immunogenicity.

Clinical trial identification

NCT05890742.

Legal entity responsible for the study

Innovent Biologics (Suzhou) Co., Ltd.

Funding

Innovent Biologics (Suzhou) Co., Ltd.

Disclosure

X. Lu, Q. Guo, H. Zhou: Financial Interests, Personal and Institutional, Full or part-time Employment: Innovent Biologics (Suzhou) Co., Ltd. All other authors have declared no conflicts of interest.