NCT07365592

Neoadjuvant Chemotherapy, Anti-PD-1 Antibody and Sitagliptin for Locally Advanced pMMR CRC

A Phase Ib/II Study of Neoadjuvant Chemotherapy Combined With Anti-PD-1 Antibody and DPP4 Inhibitor Sitagliptin for Locally Advanced pMMR Colorectal Cancer

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 138 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, multicenter, phase Ib/II combined trial of sitagliptin, XELOX chemotherapy regimen, and PD-1 monoclonal antibody in the treatment of proficient mismatch repair locally advanced colorectal cancer.

Detailed description

Most colorectal cancer (CRC) cases are classified as proficient mismatch repair (pMMR) CRC. This subtype is insensitive to single-agent immunotherapy, with chemotherapy remaining the primary pharmacotherapeutic intervention. Approximately 30% of colon cancer patients develop recurrence and metastasis following initial radical resection combined with 6 months of adjuvant chemotherapy. Neoadjuvant chemotherapy (NACT) for tumor downstaging and survival improvement represents a standard approach for locally advanced tumors. However, its application is limited to select rectal cancer populations, and its role in colon cancer remains controversial-primarily due to inadequate tumor regression observed with current regimens. Given that deep tumor regression correlates with improved survival, there is a critical need to enhance NACT efficacy. Neo-CD adopts a combined phase Ib/II study design. Phase Ib Component * Design: Single-center trial utilizing the traditional 3+3 dose-escalation principle. * Objectives: 1. Evaluate the safety of sitagliptin in combination with XELOX (oxaliplatin + capecitabine) and anti-PD-1 monoclonal antibody as neoadjuvant therapy for CRC. 2. Determine the recommended phase II dose (RP2D) of sitagliptin. 3. Explore the combination's potential for significant tumor regression and modulation of the tumor immune microenvironment. Phase II Component * Design: Prospective, multicenter, randomized controlled superiority trial. * Objective: Compare the efficacy of neoadjuvant XELOX + sitagliptin + anti-PD-1 versus standard neoadjuvant XELOX in locally advanced CRC, with a focus on significant tumor regression (TRG 0/1 rate). Study Procedures All participants will receive 2 cycles of the assigned neoadjuvant treatment, followed by radical surgery. Primary Endpoints * Phase Ib: Incidence of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicity (DLT). * Phase II: Proportion of patients achieving tumor regression grade 0/1 (TRG 0/1).

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Oxaliplatin	Oxaliplatin 130mg/m2 for inducing chemotherapy in Day 1 every 3 weeks and repeat for two cycles.
DRUG	Capecitabine	Oral Capecitabine 1000 mg/m2 twice daily combined with oxaliplatin chemotherapy in Day 1 to Day 14 every 3 weeks and repeat for 2 cycles.
DRUG	Anti-PD-1 monoclonal antibody	Anti-PD1 antibody 200mg/m2 in Day 1 after oxaliplatin Chemotherapy. Repeat every 3 weeks for 2 cycles.
DRUG	Sitagliptin (DPP4 inhibitor)	Oral sitagliptin twice daily combined with oxaliplatin chemotherapy in Day 1 to Day 14 every 3 weeks and repeat for 2 cycles. In the phase Ib study, sitagliptin set at three dose groups: 100 mg/day, 200 mg/day, and 400 mg/day, and the primary endpoint of Ib study is to determine the DLT and recommended phase II dose (RP2D). The appropriate dose level of sitagliptin will be set based on the result of Ib study.

Timeline

• Start date: 2026-01-01
• Primary completion: 2029-12-01
• Completion: 2029-12-31
• First posted: 2026-01-26
• Last updated: 2026-01-26

Locations

1 site across 1 country: China