KN 046 Plus Regorafenib in MSS Metastatic Colorectal Cancer

The study is an interventional Phase II clinical trial aiming to optimize immunotherapy strategies for microsatellite-stable colorectal cancer. We will include three types of metastatic colorectal cancer patients: those without liver metastasis, or carrying BRAF V600E mutation, or unable to tolerate chemotherapy as their initial or second-line treatment. The participants will receive a combination treatment of regorafenib and KN046 which is a PD-L1/CTLA-4 bispecific antibody. Treatment efficacy and safety profile would be evaluated in this study.

Primary Outcome Measures :

1. Overall response rate [ Time Frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose ]

2. Objective response rate (defined as CR+PR) will be reported based on investigator’s evaluation.

Secondary Outcome Measures :

1. Disease control rate [ Time Frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose ]

2. Disease control rate (defined as CR+PR+SD) will be reported based on investigator’s evaluation.

3. Progression free survival [ Time Frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose ]

4. Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) or death due to any cause.

5. Duration of response [ Time Frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose ]

6. Duration of response (DOR) is defined as the time from the date of the first response to the first objective documentation of radiographic progressive disease (PD) or death due to any cause.

7. Overall survival [ Time Frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose ]

8. Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause.

9. treatment-related adverse event [ Time Frame: Informed consent to 30 days after last dose of treatment ]

10. A treatment-related adverse event (TRAE) is defined as any adverse event not present prior to the initiation of drug treatment or any adverse event already present that worsens in intensity or frequency following exposure to the drug treatment. TRAEs were graded using National Cancer Institute (NCI)-CTCAE version 5.0.