A dual primary end point of progression-free survival in the phase 3 CheckMate-8HW trial evaluating nivolumab and ipilimumab in metastatic colorectal cancer has been met.
The combination of nivolumab (Opdivo) with ipilimumab (Yervoy) as a first-line treatment for patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer showed statistically significant and clinically meaningful improvements in progression-free survival (PFS) vs investigator’s choice of chemotherapy in the phase 3 CheckMate-8HW trial (NCT04008030).1
With these data, a dual primary end point of the phase 3 CheckMate-8HW trial has been met. Additionally, the safety profile of the combination was consistent with prior data. The combination was manageable with established protocols and no new safety signals identified.
A full evaluation of the available data from CheckMate-8HW will be completed by Bristol Myers Squibb, and the company plans to share the results with the at an upcoming medical conference, as well as with health authorities.1
“The benefits of [nivolumab] plus [ipilimumab] in MSI-H/dMMR mCRC were established previously in CheckMate-142 [NCT02060188], in which the dual immunotherapy combination demonstrated strong and durable antitumor activity among patients who had progressed after prior fluoropyrimidine-based combination chemotherapy,” said Dana Walker, MD, MSCE, vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb, in a press release. “Now, with these positive results from CheckMate-8HW, we have randomized data showing [nivolumab] plus [ipilimumab] significantly improved PFS in the first-line setting for patients with MSI-H/dMMR mCRC.
In the randomized, open-label, phase 3 CheckMate-8HW trial, the combination of nivolumab with ipilimumab is being compared with either nivolumab as a monotherapy or investigator’s choice of chemotherapy in patients with MSI-H or dMMR mCRC.2
Enrollment in the study is open to patients with known tumor MSI-H or dMMR status per local standard of practice and an ECOG performance status of 0 or 1. In part 1, patients must have histologically confirmed recurrent or metastatic CRC not amenable to surgery, irrespective of prior treatment history with chemotherapy and/or targeted agents. In part 2, patients must have histologically confirmed recurrent or metastatic CRC not amenable to surgery with no prior treatment history with chemotherapy and/or targeted agents for metastatic disease.
Investigators are evaluating the dual primary end points of PFS per blinded independent central review (BICR) for the experimental combination vs investigator’s choice of chemotherapy in the first-line setting and PFS per BICR for the combination compared with nivolumab alone across all lines of therapy. The study is ongoing and evaluating the dual primary end point of PFS in patients receiving the combination vs nivolumab alone, as well as secondary end points of overall response rate, overall survival, disease control rate, and time to response.
“These results further support the benefits of dual PD-1 and CTLA-4 inhibition, and demonstrate our continued commitment to pursue combination strategies that may help improve outcomes for patients with high unmet need,” said Walker in a press release.