NCT07281716

Combination Immunotherapy for the Treatment of Chemotherapy-refractory Metastatic MSS CRC

A Phase 1b/2 Study of Combination Immunotherapy for the Treatment of Chemotherapy-refractory Metastatic Microsatellite Stable (MSS) Colorectal Cancer (CRC)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Dan Feng · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Phase 1b/2 open-label study evaluates the safety, tolerability, and efficacy of combination immunotherapy with nadunolimab (anti-IL-1RAP) and toripalimab (anti-PD-1) in patients with chemotherapy-refractory metastatic microsatellite stable (MSS) colorectal cancer. Phase 1b will assess dose-limiting toxicity (DLT), while Phase 2 will evaluate objective response rate (ORR), including progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response (DOR). Exploratory analyses will investigate immunomodulatory effects through tumor and peripheral blood studies, and treatment will continue every 3 weeks for up to 1 year or until disease progression.

Detailed description

This is a Phase 1b/2, open-label study evaluating the safety, tolerability, and efficacy of nadunolimab (anti-IL-1RAP) in combination with toripalimab (anti-PD-1) in adults with chemotherapy-refractory metastatic microsatellite stable (MSS) colorectal cancer. The Phase 1b portion serves as a safety run-in with up to 6 subjects to assess the safety of a single dose of the combination therapy. Following this, Phase 2 will enroll up to 21 subjects, with the first 6 from Phase 1b included in the Phase 2 analysis to assess the primary efficacy endpoint. Eligible participants must have biopsy-confirmed MSS colorectal cancer (non-MSI-high or pMMR), whose disease has progressed during or following 5-FU, oxaliplatin and/or irinotecan-based chemotherapy with or without a biological agent. Subjects must have have measurable disease and tumor accessible for core needle biopsy. Participants will receive nadunolimab 5 mg/kg and toripalimab 240 mg intravenously every three weeks, continuing for up to one year or until disease progression. Primary objectives: For Phase 1/b, to determine the safety and tolerability of combination immunotherapy in subjects with chemotherapy-refractory metastatic non-MSI-high/pMMR CRC. For Phase 2, to determine the efficacy of combination immunotherapy in subjects with chemotherapy-refractory metastatic non-MSI-high/pMMR CRC as measured by the objective response rate (ORR) achieved. Subjects will undergo core needle biopsies, blood collection, and repeat imaging throughout the study. This study is conducted at Mount Sinai Hospital under IRB and PRMC oversight. The results will provide important information on the safety and potential efficacy of combining nadunolimab and toripalimab in a population with limited treatment options.

Conditions

• Metastatic Microsatellite Stable Colorectal Carcinoma

Interventions

Type	Name	Description
DRUG	Nadunolimab	5 mg/kg intravenously (IV) every 3 weeks (Q3W)
DRUG	Toripalimab	240 mg IV every 3 weeks (Q3W)

Timeline

• Start date: 2025-12-01
• Primary completion: 2028-12-15
• Completion: 2028-12-15
• First posted: 2025-12-15
• Last updated: 2026-02-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study