QL1101 in Combination With JS001 in Patients With pMMR/MSS Refractory Metastatic Colorectal Cancer

Exclusion Criteria

• •1. Have received any systemic chemotherapy within 28 days before the first study drug, or have received immunotherapy (such as interleukin, interferon, thymosin), hormone therapy, targeted therapy, or any research therapy within 14 days or 5 half-lives before the first study drug, whichever is the shorter, but immune checkpoint inhibitors are allowed to be pretreated
• •2. Received any Chinese herbal medicine or proprietary Chinese medicine for cancer control within 14 days prior to the use of the drug for the first study
• •3. Patients with primary malignancies other than bowel cancer within 5 years before randomization, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical resection,ductal carcinoma in situ after radical resection,and papillary thyroid cancer
• •4. Patients whose toxicity and side effects (due to previous anticancer treatments) have not returned to baseline or stable levels, unless such AE is not considered to pose safety risks (such as hair loss, neuropathy and abnormal results of specific laboratory tests)
• •5. Uncontrolled hypertension after treatment (systolic blood pressure ≥ 140mmHg and / or diastolic blood pressure ≥ 90mmHg). Have a history of hypertensive crisis or hypertensive encephalopathy
• •6. Any unstable systemic diseases: including but not limited to cerebrovascular accidents (transient ischemic attack, cerebral hemorrhage, cerebral infarction, etc. within 6 months before screening), deep vein thrombosis, cardiogenic chest pain (moderate pain in the 28 days before screening leads to instrumental limitation of activities of daily living), myocardial infarction (within 6 months before screening), coronary angioplasty or history of stent placement (within 6 months before screening), congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade III within 6 months before screening), symptomatic pulmonary embolism (within 28 days before screening) ), ventricular arrhythmia events with severity ≥ 2 (within 6 months before screening), syncope, seizures or falls (within 28 days before screening), poorly controlled diabetes or poorly controlled electrolyte disorders
• •7. Clinically significant third space effusion (such as a large amount of pleural effusion, ascites, pericardial effusion that cannot be controlled by pumping or other treatments)
• •8. Symptomatic central nervous system metastasis; patients with asymptomatic brain metastasis or stable symptoms after brain metastasis can participate in this study as long as they meet all the following criteria: there are measurable lesions outside the central nervous system; no midbrain, pons, cerebellum, medulla oblongata or spinal cord metastasis; no previous history of intracranial hemorrhage
• •9. The following medical history within 6 months before screening: peptic ulcer, gastrointestinal perforation, corrosive esophagitis or gastritis, inflammatory bowel disease or diverticulitis, abdominal fistula, or intra-abdominal abscess
• •10. Patients with tracheo-esophageal fistula
• •11. Patients with partial or complete bowel obstruction
• •12. Untreated patients with chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA \> 500IU/mL (or the lower limit of detection) and patients with hepatitis C virus (HCV) RNA positive should be excluded. Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBVDNA \<500IU/mL or the lower limit of detection) and cured hepatitis C patients can be selected
• •13. Human immunodeficiency virus (HIV) antibodies or syphilis testing positive
• •14. Severe chronic or active infections (according to CTCAE version 5.0, ≥ grade 3) require systemic antibacterial, antifungal or antiviral treatment, including tuberculosis j infections. Patients with a history of active tuberculosis infection ≥ 1 year before screening should also be excluded, unless proof can be provided that appropriate treatment has been completed
• •15. Patients with Child - Pugh B or more severe liver cirrhosis
• •16. Severe unhealed wound ulcers or fractures, or major surgery within 6 weeks before enrollment or expected major surgery during the study period; minor surgery within 48 hours before receiving the study drug for the first time (outpatient or inpatient surgery requiring local anesthesia，including central venipuncture catheterization); the current or recent (within 10 days before the first dose of study medication) use of aspirin for 10 days (\> 325 mg/day) or other known to inhibit platelet function of NASIDS;the current or recent (within 10 days before receiving the first study drug) use of full-dose oral or parenteral anticoagulants or thrombolytic agents, but prophylactic use of anticoagulants is allowed; have hereditary bleeding tendencies or coagulation disorders (e.g. hemophilia, coagulopathy, thrombocytopenia, etc.), or a history of thrombosis
• •17. Currently suffering from interstitial lung disease or CT showing active pneumonia during screening
• •18. History of active autoimmune disease or autoimmune disease that may recur
• •NOTE: Patients with the following diseases will not be excluded for the time being, and further screening may be carried out:
• •1. Well-controlled type I diabetes
• •2. HypothyroidismHypothyroidism (only hormone replacement therapy is needed for treatment)
• •3. Well-controlled celiac disease
• •4. Skin diseases that do not require systemic treatment (eg vitiligo, psoriasis, hair loss)
• •5. Any other diseases that are not expected to recur without external triggers
• •19. Patients with a history of allergic disease or allergic constitution
• •20. Suffer from any disease that requires corticosteroids (dose of prednisone or equivalent drugs\> 10 mg/day) or other immunosuppressive drugs for systemic treatment within ≤ 14 days before the first study drug administration
• •NOTE: patients who have used any of the following steroid treatments do not need to be excluded:
• •1. Steroids are used to replace adrenal function (prednisone or equivalent dose ≤ 10mg/ day)
• •2. Local, ocular, intra-articular, intranasal or inhaled corticosteroids with very low systemic absorption
• •3. Short-term (≤ 7 days) prophylactic use of corticosteroids (e.g. for contrast medium allergy) or for the treatment of non-autoimmune diseases (e.g. delayed type hypersensitivity caused by contact allergens)
• •21. History of primary immunodeficiency, or history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation, or history of grade 3 to 4 immune-mediated toxicity caused by other immunotherapy
• •22. Patients with a history of allergy to studied drugs or similar drugs or excipients
• •23. Patients with a history of alcohol or drug abuse who cannot be cured or who have mental disorders
• •24. Vaccination with live attenuated vaccine within 28 days before screening (including but not limited to measles, mumps and rubella vaccines, live attenuated influenza vaccine (nasal), varicella vaccine, oral polio vaccine, rotavirus vaccine, yellow fever vaccine,BCG, typhoid vaccine and typhus vaccine)
• •25. Pregnant or lactating women or women preparing to become pregnant or breastfeeding during the study
• •26. Other conditions that researchers consider inappropriate for inclusion