A Phase Ib/II Clinical Study on AK112 Combined or Not Combined With AK119 in pMMR/MSS Colorectal Cancer

Prior treatment

• Palliative local treatment for non-target lesions within 2 weeks before the first administration; Have received systemic non-specific immunomodulation therapy (such as interleukin, interferon, thymosin, etc.) within 2 weeks before the first administration; Received Chinese herbal medicine or traditional Chinese patent medicines and simple preparations with anti-tumor indications within 2 weeks before the first administration。
• Had been treated with anti-CD73 inhibitors, immune checkpoint inhibitors (such as anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists (such as antibodies against ICOS, CD40, CD137, GITR, OX40 targets, etc.), immune cell therapy (such as CAR-T) and other therapies aimed at tumor immune mechanism.
• There is a history of gastrointestinal perforation and fistula within 6 months before the first administration. If the perforation or fistula has been removed or repaired, and the researcher judges that the disease has recovered or alleviated, it can be admitted into the group.
• Active or inactive Inflammatory bowel disease (such as Crohn's disease or ulcerative colitis) previously recorded. Inability to swallow, malabsorption syndrome, or uncontrollable nausea, vomiting, diarrhea or other gastrointestinal diseases that seriously affect the use and absorption of drugs.
• Except for the tumor that the subject had at the time of enrollment, there was active malignant tumor in the previous five years. However, the tumors participating in the study and cured local tumors are excluded, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ, localized prostate cancer, etc.
• Receive the last systemic anti-tumor treatment within 3 weeks before the first administration; Received small molecular TKI treatment within 2 weeks before the first administration

Other

• Pathological examination confirmed other pathological types, such as squamous cell carcinoma, sarcoma or undifferentiated carcinoma, gastrointestinal stromal tumor, etc.
• At the same time, another interventional clinical study was enrolled.

• Be able to understand and voluntarily sign the written informed consent, which must be signed before the specified research procedure required by the research is implemented.
• Age ≥ 18 when signing the informed consent form (ICF), both male and female。
• Microsatellite stable colorectal cancer confirmed by histopathology; Microsatellite stability was defined as the expression of four common MMR proteins (MLH1, MSH2, MSH6 and PMS2) detected by immunohistochemistry, and all four proteins were positive for pMMR. Or PCR method was used to detect sites (BAT25, BAT26, D5S346, D2S123 and D17S250), and the detection results showed that the stability was microsatellite stability or microsatellite low degree instability.
• The first and second cohorts: recurrent or metastatic colorectal cancer that has failed to undergo at least the second-line standard treatment in the past; The chemotherapy of at least one of the treatment lines is the combination chemotherapy of at least two cytotoxic drugs based on platinum or irinotecan; Definition of treatment failure: disease progression occurs during or after treatment. All patients who change the treatment plan due to drug intolerance are not considered as treatment failure; For subjects who have received induction chemotherapy, concurrent radiotherapy and chemotherapy or adjuvant chemotherapy in the past, if relapse/metastasis occurs within 6 months after the last treatment, the original treatment plan is defined as the first-line treatment plan for the subject.
• The third and fourth cohorts: for patients with advanced colorectal cancer who have not undergone systematic treatment, the recurrence time should be at least 6 months from the end of the last treatment for those who have previously received induction chemotherapy, concurrent radiotherapy and chemotherapy or adjuvant/neoadjuvant chemotherapy.
• Agree to provide archived or freshly obtained tumor tissue samples within 2 years before the first administration (preferably newly obtained tumor tissue samples) About 20 unstained FFPE pathological sections (if the sample size is not enough, only 10 unstained FFPE pathological sections can be provided with the approval of medical inspectors FFPE pathological section).
• According to RECIST v1.1 standard, subjects have at least one measurable target lesion; The focus that has received radiotherapy is not selected as the target lesion, unless the radiotherapy focus is the only measurable focus and the progress is determined according to the imaging, it can be considered as the target lesion.
• The Eastern Cancer Cooperation Organization (ECOG) physical state score is 0 or 1.
• The expected survival period is ≥ 3 months.