A Study of ABT-301 Plus Tislelizumab With Bevacizumab in pMMR/​Non-MSI-H Locally Advanced or mCRC

• Drug: ABT-301
• Drug: Tislelizumab
• Drug: Bevacizumab (Avastin)

Inclusion Criteria

• Participant must be ≥18 years at the time of signing the informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..
• Participant with pMMR/non-MSI-H advancedat a late stage, far along/recurrent histologically confirmed CRC with at least one measurable lesion, per RECIST version 1.1.
• Participant must have received ≥2 lines of prior systemic therapy (including but not limited to chemotherapeutic agents of 5-fluorouracil, oxaliplatin, irinotecan; participant may or may not have received biologic agents such as cetuximab, panitumumab, aflibercept, ramucirumab, bevacizumab; tyrosine kinase inhibitors of regorafenib, fruquintinib).
  • NOTE: Participants with BRAF V600E, HER2 amplification/ mutation, KRAS G12C mutation, NTRK gene fusion, RET fusion, may or may not have received relevant targeted therapymedication that targets specific molecular features of cancer cells and failed.

• Participant must submit an archival formalin-fixed, paraffin-embedded tumor specimena sample for investigating (e.g. blood, stools, urine, sputum etc.) collected within 5 years before screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening. If archival specimens are unavailable, alternative samples, such as colonthe longest portion of the large bowel that absorbs water and salts from ingested food endoscopya procedure that involves inserting a long, flexible tube with a light and small camera (endoscope) into the body to view internal organs biopsyremoval of a section of tissue to analyse for cancer cells, are acceptable.
  • NOTE: For participants who consent to join the exploratory biomarker study, a fresh biopsy sample is required during the screening and treatment periods. Exceptions may be granted if tumor tissuea group of cells that work together to perform a function cannot be obtained due to specific circumstances.
• Tumor tissues were identified as pMMR by immunohistochemistry (IHC) method or nonMSI-H by polymerase chain reaction (PCR) (Appendix 13).
• ECOG Performance Status of 0 or 1.
• Adequate hematologic and end-organ function, defined by laboratory data obtained within 7 days prior to the first dose of study intervention:
  1. Absolute neutrophil count ≥1.5 × 109/L (1500/μL) without granulocyte colony-stimulating factor support.
  2. Lymphocyte count >0.5 × 109/L (500/µL).
  3. Platelet count >100 × 109/L (100,000/μL), without transfusion.
  4. Hemoglobin >90 g/L (9 g/dL), participants may be transfused to meet this criterion.
  5. AST, ALT, and ALP <2.5 × ULN (must be ≤5 × ULN for participants with liver metastases).
  6. Total serum bilirubin <1.5 × ULN (<3 × ULN in the presence of documented Gilbert’s syndrome [unconjugated hyperbilirubinemia] or liver metastases at baseline).
  7. Creatinine clearance >60 mL/min.
  8. Serum albumin ≥30 g/L (3 g/dL).
  9. International normalized ratio (INR) or activated partial thromboplastic time (aPTT) <1.5 × ULN.
  10. Urine dipstick for proteinuriaexcess protien in urine ≤2+ (within seven days prior to the first dose of study intervention).
• Resolution of any acutenew, recent, comes with an urgent or significant sense, is sudden, sharp, clinically significant treatment-related toxicity from prior therapy to Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells ≤1 prior to study entry, with the exception of Grade ≤2 chemotherapy-related peripheral neuropathy or any Grade alopeciathe partial or complete absence of hair from areas of the body where it normally grows; baldness.
• Participant must have a negative test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibodya protein made by the immune system to fight against harmful substances (antigens), such as bacteria or viruses, or human immunodeficiency virus (HIV) antibody.
  • NOTE: Participants with active hepatitis B virus (HBV) infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body are eligible for the study if the following applies: HBV deoxyribonucleic acid (DNA) <500 IU/mL within 28 days prior to initiation of study intervention, and anti-HBV treatment (per local standard of care, e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study. Participants with positive hepatitis C virus (HCV) test are eligible for the study if they complete their antiviral therapy prior to study entry.

• Contraceptive use by participants or participant partners must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • NOTE: The reliability of sexual abstinence for male and/or female enrollment eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception.
• Male Participants:
  • A male participant must agree to use a highly effective contraception as detailed in Appendix 4 of this protocol during the intervention period and for at least 90 days after the last dose of study intervention and refrain from donating sperm during this period.
• Female Participants:
  • A female participant is eligible to participate if she is not pregnant (see Appendix 4), not breastfeeding, and at least one of the following conditions applies:
    • Not a CBP participant as defined in Appendix 4 and below: surgically sterile (documented hysterectomycomplete or partial removal of the uterus, bilateralaffecting both sides salpingectomyremoval of one (unilateral) or both (bilateral) fallopian tubes, or bilateral oophorectomyremoval of one (unilateral) or both (bilateral) ovaries as confirmed by review of the participant’s medical records, medical examination, or medical history interview), or postmenopausal (defined as no menses for 12 months) without an alternative medical cause with follicle-stimulating hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body (FSH) level in the postmenopausal range ≥1 year.

      OR

    • A CBP participant who agrees to follow the contraceptive guidance in Appendix 4 during the intervention period and for at least 180 days after the last dose of study intervention.
• Participant is capable of giving signed informed consent as described in Appendix 1, Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.