Nivolumab demonstrates encouraging activity in metastatic colorectal cancer

CHICAGO — Nivolumab, with or without ipilimumab, appeared tolerable and demonstrated clinical activity for patients with microsatellite instability-high metastatic colorectal cancer, according to early results from the CheckMate 142 phase 2 study presented at the ASCO Annual Meeting.

“Nivolumab [Opdivo, Bristol-Myers Squibb] monotherapy demonstrated encouraging activity in patients with microsatellite instability-high status at this interim analysis and the combination of nivolumab plus ipilimumab [Yervoy, Bristol-Myers Squibb] also demonstrated promising preliminary activity,” Michael J. Overman, MD, associate professor in the department of gastrointestinal medical oncology in the cancer medicine division of The University of Texas MD Anderson Cancer Center, said during his presentation.

Because a combination of nivolumab and ipilimumab has shown promise for other solid tumor types, Overman and colleagues evaluated treatment with nivolumab with or without ipilimumab in patients with metastatic colorectal cancer who had high microsatellite instability (MSI-H; n = 56) or non–MSI-H tumors (n = 23).

Patients had an ECOG performance status of 0 to 1 and intolerance of or progression with one or more previous treatments.

Patients with MSI-H metastatic colorectal cancer received 3 mg/kg nivolumab twice per week alone (n = 33) or with 1 mg/kg ipilimumab three times per week (n = 26) for four treatment cycles. These patients then received 3 mg/kg nivolumab until disease progression.

Among patients with non–MSI-H metastatic colorectal cancer, 10 received 3 mg/kg nivolumab with 1 mg/kg of ipilimumab, 10 received 1 mg/kg nivolumab with 3 mg/kg of ipilimumab, and three received 1 mg/kg of each drug.

Eighty-two percent of patients with MSI-H colorectal cancer in the nivolumab-alone group and 92% of the nivolumab–ipilimumab group had received two or more prior regimens. All patients with non–MSI-H metastatic colorectal cancer had received at least two prior regimens.

Fifteen percent of patients with MSI-H metastatic colorectal cancer in the nivolumab-alone group and 25% of the nivolumab–ipilimumab group had known BRAF V600E mutations.

In the MSI-H cohort, 17 (52%) patients assigned nivolumab alone and 19 (73%) patients assigned nivolumab–ipilimumab remain on treatment at the time of the analysis.

Overall response rate served as the study’s primary endpoint. Secondary endpoints included OS, PFS and safety.

Among patients with non–MSI-H disease, pooled initial data for nivolumab plus ipilimumab at all three doses showed a median PFS of 1.4 months (95% CI, 1.2-1.9).

For patients with MSI-H metastatic colorectal cancer, ORR was 27% (n = 9) in the nivolumab-alone group and 15% (n = 4) in the nivolumab–ipilimumab group. No patient in either treatment cohort achieved complete response.

A greater proportion of patients in the nivolumab–ipilimumab group than the nivolumab-alone group achieved 4-month PFS (80% vs. 55%) and 5-month OS (100% vs. 75%).

Median OS was 16.3 months (95% CI, 8.3-not estimable) for the nivolumab-alone group and not reached for the combination arm. Median PFS was 5.3 months (95% CI, 1.4-not estimable) for the nivolumab-alone group and not reached for the combination group.

Treatment-related adverse events occurred in 79% (n = 26) of MSI-H patients in the nivolumab-alone group, the most common of which were diarrhea and fatigue (27% each). In the combination arm, 85% (n = 22) of patients experienced treatment-related adverse events, the most common of which was diarrhea (46%).

Seven patients in the nivolumab-alone group and eight patients in the combination arm experienced grade 3 to grade 4 treatment-related adverse events. One patient in the nivolumab-alone group experienced a grade 5 event (sudden death).

“These results support continued evaluation of nivolumab monotherapy and nivolumab plus ipilimumab in patients with MSI-H metastatic colorectal cancer and potentially other tumors with mismatch repair defects,” Overman said. – by Nick Andrews

References:

Overman MJ, et al. Abstract 3501. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclos ure: Overman reports consultant/advisory roles with Merrimack and Sirtex Medical and research funding from Amgen, Bristol-Myers Squibb, Celgene, MedImmune, Merck and Roche. Please see the abstract for a full list of all other researchers’ relevant financial disclosures.