Globally, about 10% of new cancers each year are CRC and ∼15% of these are MSI-H. Nivolumab (N), a fully human anti-PD-1 mAb, and ipilimumab (I), a humanized anti-CTLA-4 mAb, are immune checkpoint inhibitors with favorable safety and efficacy profiles in multiple tumor types. This phase 2 study evaluates N ± I in MSI-H and non-MSI-H pts with mCRC.
MSI-H pts received N 3 mg/kg q2 wk (N3) or N 3 mg/kg + I 1 mg/kg q3 wk (N3 + I1) x 4 doses followed by N3 until disease progression (PD) or other discontinuation. Initial evaluation of N + I was also completed in non-MSI-H pts. Primary endpoint was investigator-reported ORR by RECIST 1.1. Other endpoints included safety, OS, PFS, and clinical activity in biomarker-defined subpopulations (KRAS, BRAF status, and PD-L1).
70 (N3) and 30 (N3 + I1) MSI-H pts and 3 (N1 + I1), 10 (N1 + I3), and 10 (N3 + I1) non-MSI-H pts were enrolled. All non-MSI-H pts and 87% (N3) and 93% (N3 + I1) of MSI-H pts had ≥2 prior regimens. 47 (67%; N3) and 18 (60%; N3 + I1) MSI-H pts remain on tx. Efficacy data for MSI-H pts are shown in the Table. Responses were also seen in non-MSI-H pts. Median (95% CI) PFS across all non-MSI-H pts was 1.4 mo (1.2, 1.9). Responses were observed regardless of tumor PD-L1 expression. Treatment-related adverse events (TRAEs) occurred in 41 (59%; N3) and 25 (83%; N3 + I1) MSI-H pts; 10 (14%; N3) and 8 (27%; N3 + I1) pts had Grade 3–4 TRAEs. One pt on N3 had a Grade 5 TRAE (sudden death). Additional biomarker data including MSI assessment and influence of BRAF/KRAS mutations will be presented.