First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient...

Area of Science:

• Oncology
• Immunotherapy
• Gastrointestinal Oncology

Background:

• Microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) has limited treatment options after progression on standard chemotherapy.
• Nivolumab, a PD-1 inhibitor, is approved for MSI-H/dMMR mCRC post-progression, often in combination with ipilimumab.

Purpose of the Study:

• To evaluate the efficacy and safety of first-line nivolumab plus low-dose ipilimumab in patients with MSI-H/dMMR mCRC.
• To assess objective response rate (ORR) as the primary endpoint in this cohort.

Main Methods:

• Phase II CheckMate 142 study, first-line therapy cohort.
• 45 patients with previously untreated MSI-H/dMMR mCRC received nivolumab (2 weeks) + ipilimumab (6 weeks) until progression.
• Primary endpoint: ORR by investigator assessment (RECIST v1.1).

Main Results:

• Median follow-up: 29.0 months. ORR: 69% (95% CI, 53-82), Complete Response (CR): 13%.
• Median duration of response not reached; 74% ongoing at data cutoff.
• Median progression-free survival (PFS) and overall survival (OS) not reached; 24-month PFS: 74%, 24-month OS: 79%.

Conclusions:

• Nivolumab plus low-dose ipilimumab demonstrates robust and durable clinical benefit as first-line treatment for MSI-H/dMMR mCRC.
• The combination was well-tolerated, with 22% Grade 3-4 treatment-related adverse events.
• Randomized studies are warranted to confirm these promising findings.