Nivolumab Plus Ipilimumab Improves PFS in Newly Diagnosed Metastatic Colorectal Cancer

The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) per blinded independent central review (BICR) compared with investigator’s choice of chemotherapy as frontline therapy in patients with microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR) metastatic colorectal cancer (mCRC), meeting one of the dual primary end points of the phase 3 CheckMate-8HW trial.¹

At the time of the prespecified interim analysis, the combination also proved safe with no new safety signals, mirroring previously reported data with the regimen. All available data from the trial will be subject to review by Bristol Myers Squibb, who will work with investigators to share the results at a forthcoming medical meeting and with regulatory health authorities.

“The benefits of [nivolumab] plus [ipilimumab] in MSI-H/dMMR mCRC were established previously in CheckMate-142, in which the dual immunotherapy combination demonstrated strong and durable anti-tumor activity among patients who had progressed after prior fluoropyrimidine-based combination chemotherapy,” Dana Walker, MD, MSCE, vice president, global program lead in gastrointestinal and genitourinary cancers at Bristol Myers Squibb, stated in a news release.

The randomized, open-label, phase 3 CheckMate-8HW trial is evaluating nivolumab plus ipilimumab vs nivolumab alone or investigator’s choice chemotherapy consisting of mFOLFOX6 or FOLFIRI with or without bevacizumab (Avastin) or cetuximab (Erbitux) in patients with MSI-H/dMMR mCRC.

To be eligible for enrollment in part 1 of the study, patients had to have histologically confirmed recurrent or mCRC not fit for surgery, regardless of prior treatment exposure to chemotherapy and/or targeted therapy. In part 2, patients had to have histologically confirmed recurrent or mCRC unfit for surgery, with no prior therapy with chemotherapy and/or targeted agents in the metastatic setting. Known tumor MSI-H/dMMR status per local standards and an ECOG performance status of 0 or 1 were also required.²

Patients with active, known, or suspected autoimmune disease, history of interstitial lung disease or pneumonitis, and known history of HIV positivity or AIDS were excluded from enrollment among other protocol-defined criteria.

Approximately 830 patients were randomly assigned to receive 240 mg of nivolumab monotherapy every 2 weeks for 6 weeks, followed by 480 mg every 4 weeks; 240 mg of nivolumab plus 1 mg/kg of ipilimumab every 3 weeks for 4 weeks, followed by 480 mg of nivolumab every 4 weeks, or investigator’s choice of chemotherapy.¹

PFS per BICR for the combination vs investigator’s choice of chemotherapy in the first-line setting as well as for the combination vs nivolumab alone across all lines of therapy serve as the dual primary end points of the trial. Key secondary end points include overall response rate by BICR, overall survival, and investigator-assessed PFS.²

The study will continue to evaluate the second dual primary end point of PFS for the combination vs nivolumab alone across all lines of therapy as well as secondary end points.¹

“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. 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.”

References

1. Bristol Myers Squibb announces phase 3 CheckMate -8HW trial evaluating opdivo (nivolumab) plus yervoy (ipilimumab) compared to chemotherapy in microsatellite instability–high or mismatch repair deficient metastatic colorectal cancer meets primary... News release. Bristol Myers Squibb. December 7, 2023. Accessed December 7, 2023. https://news.bms.com/news/corporate-financial/2023/Bristol-Myers-Squibb-Announces-Phase-3-CheckMate--8HW-Trial-Evaluating-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Compared-to-Chemotherapy-in-Microsatellite-InstabilityHigh-or-Mismatch-Repair-Deficient-Metastatic-Colorectal-Cancer-Meets-Primary/default.aspx
2. A study of nivolumab, nivolumab plus ipilimumab, or investigator's choice chemotherapy for the treatment of participants with deficient mismatch repair (dMMR)/​microsatellite instability high (MSI-H) metastatic colorectal cancer (mCRC) (CheckMate 8HW). ClinicalTrials.gov. Updated October 27, 2023. Accessed December 7, 2023. https://www.clinicaltrials.gov/study/NCT04008030