Nivolumab and ipilimumab improve PFS in newly diagnosed metastatic colorectal cancer

The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) improved progression-free survival (PFS) by blinded independent central review (BICR) compared to the chemotherapy chosen by investigators as front-line treatment for microsatellite patients. resulted in statistically significant and clinically meaningful improvements in Meets one of the two primary endpoints of the Phase 3 CheckMate-8HW study in unstable-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC).¹

As of a prespecified interim analysis, the combination was proven to be safe with no new safety signals, mirroring previously reported data in this regimen. All available data from the trial will be subject to review by Bristol-Myers Squibb, which will work with researchers and share findings at future medical meetings and regulatory health authorities.

“The following benefits [nivolumab] plus [ipilimumab] mCRC was previously established in MSI-H/dMMR. CheckMate-142, dual immunotherapy combination demonstrates potent and sustained antitumor activity “This occurred among patients who had progressed after prior fluoropyrimidine-based combination chemotherapy,” said Dana Walker, M.D., vice president and global program leader for gastrointestinal and genitourinary cancers at Bristol-Myers Squibb. , MSCE said in a news release.

The randomized, open-label, phase 3 CheckMate-8HW study tested nivolumab plus ipilimumab plus nivolumab alone, or mFOLFOX6 or mFOLFOX6 with or without bevacizumab (Avastin) or cetuximab (Erbitux) in patients with MSI-H/dMMR. We are evaluating investigator-selected chemotherapy consisting of FOLFIRI. mCRC.

To be eligible for enrollment in Part 1 of the study, patients were required to have histologically confirmed mCRC that was recurrent or unsuitable for surgery, regardless of prior treatment history with chemotherapy and/or targeted therapy. Part 2 included patients with histologically confirmed mCRC that was recurrent or unsuitable for surgery and had not been treated with chemotherapy and/or targeted agents if metastatic. Known tumor MSI-H/dMMR status according to regional criteria and ECOG performance status of 0 or 1 were also required.²

Patients with active, known, or suspected autoimmune disease, a history of interstitial lung disease or pneumonia, and a known history of HIV-positive or AIDS should be treated with other protocols. were excluded from registration even within the criteria defined in .

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

PFS per BICR for combination therapy and investigator-selected chemotherapy in the first-line setting and combination therapy and nivolumab alone for all treatments will serve as dual primary endpoints for this trial. Key secondary endpoints include overall response rate by BICR, overall survival, and investigator-assessed PFS.²

This study will continue to evaluate the second dual primary endpoint of PFS for combination therapy and nivolumab monotherapy across all treatments, as well as secondary endpoints.¹

“With these positive results from CheckMate-8HW, the randomized data is as follows: [nivolumab] plus [ipilimumab] PFS was significantly improved in the primary care setting for MSI-H/dMMR mCRC patients. These results further support the benefits of dual inhibition of PD-1 and CTLA-4 and extend our continued pursuit of combination strategies that may help improve outcomes in patients with high unmet need. It shows our efforts. ”

References

1. Bristol-Myers Squibb Announces Phase 3 CheckMate -8HW Study Evaluating Opdivo (nivolumab) and Yervoy (ipilimumab) Compared to Chemotherapy in Microsatellite Instability – High or Mismatch Repair-Deficient Metastatic Colon Rectal cancer and primary…News release. Bristol-Myers Squibb Company. 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-Comparated -High instability to chemotherapy in microsatellites or primary metastatic colorectal cancer with failure to repair mismatch/default.aspx
2. Nivolumab, nivolumab plus ipilimumab, or investigator-selected chemistry for the treatment of participants with mismatch repair deficient (dMMR)/microsatellite instability high (MSI-H) metastatic colorectal cancer (mCRC) Therapy Research (CheckMate 8HW). ClinicalTrials.gov. Updated October 27, 2023. Accessed December 7, 2023. https://www.clinicaltrials.gov/study/NCT04008030