KEY TAKEAWAYS
- Phase 3 trial CheckMate-142 evaluated the efficacy and safety of NIVO ± IPI in previously treated patients 2L+ and as first-line therapy 1L for MSI-H/dMMR mCRC.
- The primary endpoint was ORR by INV per RECIST v1.1. Critical endpoints were DCR, DOR, PFS, OS, and safety.
- The study was a non-randomized, multicohort study with 74 patients in C1, 119 in C2, and 45 in C3.
- The ORR (95% CI) by INV was 39% (28–51) in C1, 65% (55–73) in C2, and 71% (56–84) in C3. Median DOR was not reached in the 3 cohorts.
- With an extended follow-up of ~5 years, NIVO ± IPI demonstrated durable OS and PFS benefits with no new safety signals.
- These updated data further support the current treatment recommendations for patients for 2L+ NIVO ± IPI and 1L NIVO + IPI.
The phase 2 CheckMate-142 research provided the evidence needed to approve NIVO ± IPI in previously treated patients with MSI-H/dMMR mCRC in the United States, the European Union, and Japan (NCT02060188). Patients diagnosed with MSI-H/dMMR mCRC have NIVO + IPI as an initial treatment choice under NCCN guidelines. Here, researchers presented data from a roughly five-year follow-up of CheckMate-142 Cohorts 1 through 3 (C1-3). Patients with MSI-H/dMMR mCRC were randomized to receive either C1 (2L+; NIVO 3 mg/kg Q2W), C2 (2L+; NIVO 3 mg/kg + IPI 1 mg/kg Q3W [4 doses], followed by NIVO 3 mg/kg Q2W), or C3 (1L; NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W), until disease progression or unacceptable toxicity. The primary outcome measure was the objective response rate (ORR) determined by the investigator using RECIST v1.1. Additional important outcomes included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), and safety as assessed by INV and blinded independent central review.
Median (range) follow-up (time from first dosage to data cutoff) was 70.0 (66.2-88.7) months (mo) in C1 (N = 74), 64.0 months (mo) in C2 (N = 119), and 52.4 months (mo) in C3 (N = 45). Overall response rates (95% CI) by INV were 39% (28-51), 65% (55-73), and 71% (56-84); Table), and PD rates were 26% (12%), 16% (8%), and 16% (0%), respectively. The 3 cohorts did not attain the median DOR. 48-month progression-free survival (PFS) rates for C1, C2, and C3 were 36%, 54%, and 51%, respectively. Extended follow-up of ~5 years showed that the OS and PFS benefits seen with NIVO ± IPI persisted. These newly available results lend even more credence to the established therapy guidelines for patients with MSI-H/dMMR mCRC, which call for 2L+ NIVO ± IPI or 1L NIVO + IPI.
Source: https://meetings.asco.org/abstracts-presentations/208415
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02060188
Michael J. Overman, Heinz-Josef Lenz, Thierry Andre, Massimo Aglietta, Mark Ka Wong, Gabriele Luppi, Eric Van Cutsem, Raymond S. McDermott, Alain Hendlisz, Dana Backlund Cardin, Michael Morse, Bart Neyns, Andrew Graham Hill, M. Luisa Limon, Pilar Garcia-Alfonso, Anuradha Krishnamurthy, Franklin Chen, Sandzhar Abdullaev, Samira Soleymani, Sara Lonardi/Nivolumab (NIVO) ± ipilimumab (IPI) in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Five-year follow-up from CheckMate 142/J Clin Oncol 40, 2022 (suppl 16; abstr 3510) DOI10.1200/JCO.2022.40.16_suppl.3510
