NCT06646445

Neoadjuvant Pembrolizumab With a Watch-and-wait Strategy for dMMR/MSI-H Localized Colon Cancer: PREMICES Study.

Neoadjuvant Pembrolizumab With a Watch-and-wait Strategy for Patients With Mismatch Repair-deficient or Microsatellite Instability-high (dMMR/MSI-H) Localized Colon Cancer: a Randomized GERCOR G-109 PRODIGE 84 PREMICES Phase II Trial

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this investigational, multicenter, open-label randomized, two-stage phase II study is to evaluate neoadjuvant pembrolizumab with a watch-and-wait approach in patients with localized deficient mismatch repair / high microsatellite instability (dMMR/MSI-H) colorectal cancer (CRC). The PREMICES trial is based on the hypothesis that non-operative management is effective for dMMR/MSI-H localized CRC when treated with neoadjuvant pembrolizumab. Eligible patients will be randomized in a 1:1 ratio to receive either pembrolizumab with a watch-and-wait approach (experimental arm A) or the standard strategy of surgical resection ± adjuvant chemotherapy (arm B).

Detailed description

dMMR/MSI-H is a key biomarker for predicting the success of immune checkpoint inhibitors in colorectal cancer (CRC). Pembrolizumab has shown improved outcomes for patients with metastatic CRC, becoming the new standard of care. Neoadjuvant immunotherapy has demonstrated high rates of complete pathological responses in both metastatic and localized CRC, with promising results in non-surgical approaches. Studies support using a "watch-and-wait" strategy after immunotherapy, potentially avoiding surgery. These findings are reshaping treatment strategies for dMMR/MSI-H CRC, particularly regarding organ preservation and non-operative management. The PREMICES study evaluates the efficacy of neoadjuvant pembrolizumab combined with a watch-and-wait approach for treating localized dMMR/MSI-H CRC. It investigates non-operative management as a potential strategy for achieving a complete clinical response in dMMR/MSI-H localized CRC without the need for surgery.

Conditions

• Colon Cancer

Interventions

Type	Name	Description
DRUG	Pembrolizumab Injection [Keytruda]	Pembrolizumab 200 mg via a 30-minute IV infusion q3w on Day 1 of each 21-day cycle; 8 cycles ± 9 additional cycles (17 cycles in total).
PROCEDURE	Watch-and-wait approach	Watch-and-wait strategy: * TAP-CT scan At months 3 and 6 during 8 cycles of treatment, at months 9 and 12, and during additional 9 cycles of treatment if performed, and every 3 months thereafter for up to 2 years, * Colonoscopy with biopsies at months 3, 6, 9, 12, and 24.
PROCEDURE	Surgery	Standard of care surgery performed with a maximal delay of 21 days (3 weeks) from randomization.
DRUG	Adjuvant chemotherapy	Adjuvant chemotherapy (5-fluorouracil/capecitabine ± oxaliplatin 3 months to 6 months) according to the current guidelines, at the investigator's discretion.

Timeline

• Start date: 2025-09-01
• Primary completion: 2027-12-01
• Completion: 2029-12-01
• First posted: 2024-10-17
• Last updated: 2025-06-13

Locations

10 sites across 1 country: France