KEY TAKEAWAYS
- CheckMate 8HW is a phase 3, international, multicenter, open-label, randomized trial.
- The study’s primary aim is to compare the efficacy and safety of NIVO+IPI to chemotherapy or NIVO in patients with MSI-H/dMMR mCRC.
- Approximately 748 patients across 23 countries will be randomized to receive NIVO, NIVO+IPI, or investigator’s choice chemotherapy.
- The dual primary endpoints are PFS for NIVO+IPI vs. NIVO across all lines and NIVO+IPI vs. chemotherapy in the first-line setting in patients with centrally confirmed MSI-H/dMMR mCRC. Other critical endpoints include PFS, ORR, OS, and safety.
- The study will assess the efficacy of NIVO+IPI vs. NIVO in the first-line setting and in previously treated patients.
- Recruitment of patients in the first-line setting is ongoing, and the trial is registered under NCT04008030.
Chemotherapy is less effective for patients with MSI-H/dMMR mCRC than those with microsatellite stable/MMR proficient mCRC. In multiple countries, Pembrolizumab monotherapy is approved as first-line therapy for MSI-H/dMMR mCRC. Still, the 24-month progression-free survival (PFS) rate was only 48% despite observed clinical benefit versus chemotherapy (Andre et al. NEJM 2020). Immune checkpoint inhibitors like [anti-programmed death 1 (PD-1)] and [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4)] have different mechanisms that work in tandem. Results from the phase 2, non-randomized, multicohort CheckMate 142 study led to the approval of NIVO±IPI in previously treated patients with MSI-H/dMMR mCRC in the United States, the European Union, and Japan. Indirect comparisons suggest that the benefit-risk profile for previously treated MSI-H/dMMR mCRC is more favorable with NIVO (3 mg/kg) + IPI (1 mg/kg) compared to NIVO alone (INV objective response rate [ORR] 55% vs. 31%; 12-month INV progression-free survival [PFS] rate 71% vs. 50%; 12-month INV overall survival [OS] rate 85% vs. 73%).
(Overman et al. JCO 2018). INV ORR 69%; 24-month INV PFS rate 74%; 24-month OS rate 79%; Lenz et al., JCO 2022; NIVO+IPI demonstrated robust and durable clinical benefit and was well tolerated for the first-line treatment of MSI-H/dMMR mCRC. For patients with MSI-H/dMMR mCRC, CheckMate 8HW (NCT04008030) is an international, multicenter, open-label, randomized, phase 3 study comparing the efficacy and safety of NIVO+IPI to chemotherapy or NIVO.
Roughly 748 patients in 23 countries will be randomly assigned to receive either NIVO, NIVO+IPI, or investigator’s choice chemotherapy (patients in the chemotherapy arm can receive NIVO+IPI upon progression) for their histologically confirmed recurrent or mCRC that is not amenable to surgery, regardless of prior treatment with chemotherapy and/or targeted agents. Primary endpoints include progression-free survival (PFS) by blinded independent central review (BICR) for NIVO+IPI vs. NIVO across all lines and NIVO+IPI vs. chemotherapy in the first-line setting in patients with centrally confirmed MSI-H/dMMR mCRC. Secondary endpoints include PFS by INV, objective response rate (ORR) by BICR, overall survival (OS), and safety. Patient enrollment in the primary care setting is ongoing.
Source:https://www.annalsofoncology.org/article/S0923-7534(22)00794-3/fulltext#secsectitle0020
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT04008030
André, T., Van Cutsem, E., Elez, E., Bennouna, J., de la Fouchardière, C., Yoshino, T., Jensen, L., Mendez, G., Li, J., Goekkurt, E., Abdullaev, S., Chen, T., Lei, M., & Lonardi, S. (2022). P-12 A phase 3 study of nivolumab (NIVO), NIVO + ipilimumab (IPI), or chemotherapy for microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC): CheckMate 8HW. Annals of Oncology, 33, S250. https://doi.org/10.1016/j.annonc.2022.04.104
