In a single-arm cohort of a phase II study (cohort 2 of Checkmate-142), nivolumab in combination with ipilimumab was associated with clinically relevant overall response rates in adults with dMMR or MSI-H metastatic colorectal cancer who had received prior fluoropyrimidine-based chemotherapy. The submitting company presented a cost-utility analysis evaluating the use of nivolumab-ipilimumab within its full licensed indication. The analysis compared nivolumab-ipilimumab with BSC, trifluridine-tipiracil, FOLFOX and FOLFIRI through unanchored MAIC. Clinical experts indicated that FOLFOX and FOLFIRI were the most appropriate comparators. There were a number of weaknesses with the analysis: • Median PFS and OS were not reached, and the PFS and OS are therefore uncertain. The extrapolations applied in the model had good statistical and visual fit. The alternative extrapolations were explored in scenarios and did not change the ICER drastically. Further, there were limitations associated with the indirect treatment comparisons upon which the economic evaluation was based; • Health Utility Index HUI values were used to derive the comparator health effects and it may not be appropriate to compare with EQ-5D-3L values for nivolumab-ipilimumab in order to reflect the true difference in health effects; • The on treatment utility for nivolumab-ipilimumab may be unrealistically high, though the impact of the on treatment utility in sensitivity analyses is minimal. The company explored a scenario when applying equal utility values between nivolumab-ipilimumab and comparators. This resulted in a reduced ICER due to the differences in PFS between arms; • Some subsequent treatments included are not available in NHS Scotland, though the impact of these would be minimal based on scenario analyses. Despite these limitations, the economic case was demonstrated.