A Phase II Multi-cohort Clinical Study Evaluating The Efficacy and Safety of KN046 in Combination With Regorafenib for Metastatic Microsatellite-Stable Colorectal Cancer: a Phase II Multi-cohort Study
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.
• I01. Subjects are able to comprehend the informed consent form, voluntarily participate, and sign the informed consent form.
• I02. Subjects are ≥18 years old on the day of signing the informed consent form, with no gender restrictions.
• I03. Histologically confirmed colorectal adenocarcinoma, including signet ring cell carcinoma and mucinous adenocarcinoma.
• I04. According to RECIST 1.1 criteria, there should be at least one measurable or evaluable lesion at baseline. If the subject has only one measurable or evaluable lesion at baseline, the lesion must not have been exposed to radiotherapy previously, or there must be evidence of significant progression after radiotherapy treatment completion.
• I05. ECOG performance status of 0 or 1. I06. Expected survival ≥3 months. I07. Archived tumor tissue samples or freshly obtained tumor tissue samples are available.
• I08. Female subjects of childbearing potential or male subjects with partners of childbearing potential agree to use highly effective contraception from 7 days before the first dose until 120 days after the last dose. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose.
• I09. Subjects have the ability and willingness to comply with the study protocol's visits, treatment plan, laboratory tests, and other study-related procedures.
• I10. Within the first 7 days of initial dosing, subjects should have good organ function:
• HGB ≥ 80g/L NEU ≥ 1.0\*10\^9/L PLT ≥ 75\*10\^9/L Cr≤1.5×ULN or CrCl≥50mL/min（ Cockcroft-Gault method） TBiL ≤ 1.5×ULN ALT and AST ≤3 ×ULN； for patients with liver metastasis ALT and AST ≤5 ×ULN urine protein \<2+；if urine protein ≥ 2+，24 hour urinary protein quantity \<2g； INR， APTT，PT ≤ 1.5 ×ULN
• I11. For each cohort, the previous treatment history must meet the following conditions:
• Cohort A: pMMR/MSS mCRC with no BRAF V600E mutation, who failed fluoropyrimidine, oxaliplatin, and irinotecan treatments, and without definitive active liver metastases at enrollment (judged by the investigator based on medical history and imaging).
• Cohort B: pMMR/MSS mCRC with BRAF V600E mutation, who failed fluoropyrimidine, oxaliplatin, and irinotecan treatments.
• Cohort C: MSS mCRC that has not intolerant or unsuitable for or refuse to receive standard first-line or second-line chemotherapy.