Nivolumab/Ipilimumab Earns CHMP Recommendation for Colorectal Cancer

The CHMP recommended for approval nivolumab/ipilimumab for patients with MSI-H and dMMR unresectable or metastatic colorectal cancer.

Approval of nivolumab (Opdivo) plus ipilimumab (Yervoy) as a first-line treatment in adult patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer has been recommended by the European Medicines Agency (EMAs) Committee for Medicinal Products for Human Use (CHMP), according to a press release from Bristol Myers Squibb.¹

The next step includes the European Commission (EC) reviewing the recommendation and deciding if it should be approved for treatment.

“This is the first dual checkpoint inhibitor treatment for first-line metastatic colorectal cancer, delivering a transformative benefit for MSI-H/dMMR patients in this population,” Dana Walker, MD, MSCE, vice president and global program lead at Bristol Myers Squibb said. “We are focused on bringing [nivolumab] and [ipilimumab] to these patients in the European Union and look forward to EC’s upcoming decision.”

Results from the phase 3 randomized, open-label CheckMate-8HW trial (NCT04008030) found a significant and meaningful improvement in progression-free survival (PFS), without adding any new safety signals.

In January 2024, promising results were reported at the 2024 Gastrointestinal Cancers Symposium.² At the median follow-up of 24.3 months, the combination regimen showed a clinically meaningful and statistically significant improvement in PFS (not reached; 95% CI, 38.4-not evaluable) vs the chemotherapy group (5.9 months; 95% CI, 4.4-7.8). There was also reduction in the risk of disease progression or death by 79% (HR, 0.21; 95% CI, 0.14-0.32; P <.0001) compared with chemotherapy.

Additionally, it was announced in October 2024 that nivolumab plus ipilimumab yielded meaningful improvement in PFS per blinded independent central review (BICR) compared with the nivolumab monotherapy group.

A total of 839 patients were randomly assigned in a 2:2:1 fashion and given 240 mg of nivolumab plus 1 mg/kg of ipilimumab every 3 weeks for 4 doses followed by 480 mg of nivolumab every 4 weeks, followed by 240 mg of nivolumab every 4 weeks, then 240 mg of nivolumab every 2 weeks for 6 doses, and 480 mg every 4 weeks. In the comparator arm, patients were given chemotherapy with or without targeted therapies.

Part 1 is open to patients with histologically confirmed recurrent or metastatic colorectal cancer not amenable to surgery, irrespective of prior treatment history with chemotherapy and/or targeted agents. Enrollment for part 2 requires histologically confirmed recurrent or metastatic colorectal cancer but with no prior history of treatment with chemotherapy and/or targeted agents for metastatic disease. Patients in both parts were required to have an ECOG score of 0 or 1.

Regarding participation, an active, known, or suspected autoimmune disease, history of interstitial lung disease or pneumonitis, and history of a positive test for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) were criteria for exclusion.

The safety profile for the nivolumab plus ipilimumab regimen was manageable and consistent with previous data. Treatment-related adverse events (TRAEs) were observed in 160 of 200 patients (80%) in the combination regimen group, with 38 (19%) being serious and 83 of 88 patients (94%) in the chemotherapy group, with 17 (19%) being serious.

Any grade TRAEs that led to discontinuation of study treatment were reported in 33 patients (17%) in the combination regimen group and 28 patients (32%) in the chemotherapy group. Grade 3/4 TRAEs that led to discontinuation occurred for 23 patients (12%) and 9 patients (10%), respectively.

The trial remains ongoing and continues to evaluate additional end points, including overall survival. Further data disclosure is planned for an upcoming medical conference.

References

1. Bristol Myers Squibb receives positive CHMP opinion for Opdivo® (nivolumab) plus Yervoy® (ipilimumab) for the first-line treatment of adult patients with microsatellite instability–high or mismatch repair deficient metastatic colorectal cancer. News Release. Bristol Myers Squibb. November 15, 2024. Accessed November 18, 2024. https://tinyurl.com/434jvfcu
2. Andre T, Elez E, Van Cutsem E, et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): First results of the CheckMate 8HW study. Presented at the 2024 Gastrointestinal Cancers Symposium; San Francisco, CA, January 18-20, 2024. LBA 768.