▎WuXi AppTec Content Team Report

Colorectal cancer (CRC) is a malignant tumor that occurs in the colon or rectum, both of which are parts of the human digestive system. The dMMR phenotype occurs when proteins responsible for repairing mismatch errors during DNA replication are missing or lose function, leading to MSI-H tumors. Public data shows that approximately 5% to 7% of patients with metastatic colorectal cancer have dMMR or MSI-H tumors. These patients are less likely to benefit from traditional chemotherapy and generally have a poorer prognosis.

Ipilimumab is a CTLA-4 antibody, and nivolumab is a PD-1 inhibitor.In March 2024, the dual immunotherapy combination was included by the CDE as a breakthrough therapy. In the same month, the dual immunotherapy combination was also granted priority review by the CDE forFirst-line treatment for colorectal cancer. This is precisely the indication for which this combination therapy was approved this time.

According to the press release from Bristol-Myers Squibb, this approval is based onCheckMate-8HW Study Results.In January 2024, Bristol-Myers Squibb orally presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.The StudyThe latest data. This is a Phase 3 randomized, open-label study evaluating nivolumab combined with ipilimumab (dual immunotherapy group) compared to nivolumab monotherapy or investigator's choice of chemotherapy regimen (mFOLFOX-6 or FOLFIRI, with or without bevacizumab or cetuximab) for treatment.Patients with MSI-H or dMMR phenotype metastatic colorectal cancerThe efficacy. Approximately 830 patients were randomly assigned to the nivolumab monotherapy group, the nivolumab plus ipilimumab group, or the investigator's choice of chemotherapy regimen.

According to the assessment by the Blinded Independent Central Review (BICR), the dual immunotherapy combination demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS):Compared with chemotherapy, as a first-line treatment for mCRC patients with MSI-H/dMMR phenotype confirmed by central laboratory testing,Reduced the risk of disease progression or death by 79%。

In addition, the dual immunotherapy combination groupPFS improvement began to appear at about three months, and贯穿始终. The median PFS in the combination therapy group has not been reached, while in the chemotherapy group it was 5.9 months. A consistent PFS benefit was observed across all pre-specified subgroups, including those withKRASOrNRASMutationPatients, as well as those with baseline liver, lung, or peritoneal metastases. The safety profile of the combination therapy was consistent with previously reported data, manageable under the established study protocol, with no new safety signals identified.

Currently, the CheckMate-8HW study is still ongoing to evaluate the second dual primary endpoint, which isAll treatment linesPFS in patients receiving dual immunotherapy compared to nivolumab monotherapy in China; secondary endpoints will also be assessed.

References:

[1] World's First! "Immune Twin Stars" Approved in China for First-Line Treatment of MSI-H/dMMR mCRC. Retrieved Oct 14, 2024, from https://mp.weixin.qq.com/s/YaSnWutC6532p3cjLopnkg

[2] 79% Reduction in Risk of Progression or Death! CheckMate-8HW Study Results Stun the World. Retrieved Jan 22, 2024 from https://mp.weixin.qq.com/s/aWWPS3ylaCAyjn50A4qWPQ