Concordance of DNA mismatch repair deficient (dMMR)/microsatellite instability (MSI) assessment by local and central testing in patients with metastatic CRC (mCRC) receiving nivolumab (nivo) in CheckMate 142 study.

Background: MMR or MSI testing is recommended for mCRC pts and is often done locally by IHC or PCR testing, respectively (NCCN V1.2017) Nivo, a fully human anti-PD-1 mAb, demonstrated durable responses and a 12-mo OS rate of 73.8% in pts with mCRC locally assessed for dMMR/MSI-H status in the CheckMate 142 study (NCT02060188; Overman M, et al. 2017). Here we describe the results of local and central testing with respect to MMR/MSI status and clinical outcomes in the CheckMate 142 study. Methods: MMR/MSI status was assessed locally on archival tumor using IHC/PCR at screening and confirmed centrally by PCR (modified Bethesda panel) testing of tumor biopsy at enrollment. dMMR was defined by IHC as a loss of expression in ≥1 mismatch repair proteins. Stable microsatellite (MSS), low MSI (MSI-L), and high MSI (MSI-H), were defined as instability in 0, 1, or ≥2 markers, respectively. Pts with dMMR/MSI-H mCRC who progressed on or were intolerant of ≥1 prior line of therapy received nivo 3 mg/kg Q2W. Results: 74 pts were dMMR/MSI-H by local testing. Of these pts, 53 (72%) were centrally confirmed as MSI-H, 7 pts had insufficient tissue sample for PCR testing, and 14 pts had a central test that did not match local test results. Of the 14 pts, 3 pts with a clinical history of LS were identified locally as dMMR but centrally as MSS (Table). INV-reported ORR was 31.1% in 74 pts locally determined as dMMR/MSI-H, 35.8% in 53 pts locally and centrally confirmed as MSI-H, and 21.4% in 14 pts not centrally confirmed as MSI-H. Conclusions: The similar clinical activity between pts locally confirmed as MSI-H and pts who were centrally confirmed as MSI-H suggest local testing is appropriate for identifying the dMMR/MSI-H pts who may benefit from nivo monotherapy. Clinical trial information: NCT02060188.

Pt Local Testing
Central Testing Clinical History of LS
Method Result
1 IHC dMMR MSS NA
2 IHC dMMR MSS No
3 IHC dMMR MSS Yes
4 IHC dMMR MSS Yes
5 IHC/PCR dMMR (IHC)/MSI-H (PCR) MSS NA
6 IHC dMMR MSS Yes
7 IHC dMMR MSS No
8 PCR MSI-H MSS NA
9 IHC/PCR dMMR (IHC)/MSI-H (PCR) MSS NA
10 IHC dMMR MSS No
11 IHC dMMR MSS NA
12 PCR MSI-H MSS NA
13 IHC dMMR MSI-L NA
14 IHC dMMR MSS NA
NA = not available.