Saint-Antoine Hospital, Paris, France
Thierry Andre , Sara Lonardi , Mark Wong , Heinz-Josef Lenz , Fabio Gelsomino , Massimo Aglietta , Michael Morse , Eric Van Cutsem , Raymond S. McDermott , Andrew G Hill , Michael B. Sawyer , Alain Hendlisz , Bart Neyns , Magali Svrcek , Rebecca Anne Moss , Jean-Marie Ledeine , Z. Alexander Cao , Shital Kamble , Scott Kopetz , Michael J. Overman
Background: Nivolumab (NIVO) provided durable responses (investigator-assessed [INV] ORR, 31%) and disease control (DCR, 69%) in pretreated pts with dMMR/MSI-H mCRC in CheckMate-142 (NCT02060188; Overman et al Lancet Oncol 2017). An interim analysis of the NIVO + ipilimumab (IPI) combination cohort of CheckMate-142 reported a preliminary ORR of 55% and manageable safety profile in a subset of pts (n = 84) with dMMR/MSI-H mCRC and ≥ 6 mo of follow-up (André et al ASCO 2017). Here we report for the first time efficacy and safety from the complete population (N = 119) of the NIVO + IPI cohort of CheckMate-142, which is the largest single-study report of an immunotherapy regimen in pts with dMMR/MSI-H mCRC. Methods: Pts with dMMR/MSI-H mCRC received NIVO 3 mg/kg + IPI 1 mg/kg Q3W for 4 doses followed by NIVO 3 mg/kg Q2W. Primary endpoint was ORR (INV; RECIST 1.1). Other endpoints were DOR, PFS, OS, and safety/tolerability. Results: Of 119 treated pts, 76% had ≥ 2 prior lines of therapy. Median follow-up was 13.4 mo. The ORR was 55% and DCR was 80% (Table). Notably, ORR in pts with a BRAF mutation was 55%. Among all responders, median DOR was not reached (NR), with 94% of responses ongoing at data cutoff. Tumor burden was reduced from baseline in 77% of pts. The 9-mo PFS and OS rates were 76% and 87%, respectively. Gr 3–4 TRAEs occurred in 32% of pts; 13% (any gr) and 10% (gr 3–4) of pts had TRAEs that led to discontinuation. No treatment-related deaths were reported. Results including a similar follow-up of the NIVO arm will also be presented. Conclusions: In the largest cohort of dMMR/MSI-H pts treated with an immunotherapy regimen, NIVO + IPI built on the efficacy reported with NIVO monotherapy, demonstrating enhanced clinical benefit and manageable safety, and may represent a new standard of care in pts with dMMR/MSI-H mCRC. Clinical trial information: NCT02060188
NIVO + IPI (N = 119) | |
---|---|
ORR, n (%) 95% CI | 65 (55) 45.2, 63.8 |
CR | 4 (3) |
PR | 61 (51) |
SD | 37 (31) |
PD | 14 (12) |
Unknown | 3 (3) |
DCR, n (%)a 95% CI | 95 (80) 71.5, 86.6 |
Median DOR [95% CI], mo | NR [NE] |
Median PFS [95% CI], mo 9-mo rate, % | NR [NE] 76 |
Median OS [95% CI], mo 9-mo rate, % | NR [NE] 87 |
NE = not estimable
aCR + PR + SD ≥ 12 wk
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Abstract Disclosures
2023 ASCO Annual Meeting
First Author: Heinz-Josef Lenz
2024 ASCO Gastrointestinal Cancers Symposium
First Author: Thierry Andre
2022 ASCO Annual Meeting
First Author: Michael J. Overman
2023 ASCO Annual Meeting
First Author: Dirk Schadendorf