A Clinical Study to Evaluate Injection TQB2102 for the Treatment of Patients With HER2 IHC3+ Advanced Colorectal Cancer Who Progressed After Treatment With Oxaliplatin, Irinotecan and Fluoropyrimidine-Based Drugs

Prior treatment

• Receipt of major surgical treatment, significant traumatic injury within 4 weeks prior to the first dose; or planned major surgery during the study period (excluding surgeries specified in the protocol); or presence of unhealed wounds or fractures for a prolonged period.
• Clinically significant tumor bleeding or perforation within 1 month prior to the first dose; or any bleeding event ≥ Grade 3 per CTCAE v5.0; or subjects with bleeding or coagulation disorders receiving warfarin, aspirin, or other antiplatelet agents (excluding maintenance doses: aspirin ≤ 100 mg/day, clopidogrel ≤ 75 mg/day); or subjects with a history or signs of bleeding deemed ineligible by the investigator.
• A history of thrombotic or embolic events within 6 months prior to the first dose, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis (DVT) \[excluding subjects with isolated calf vein thrombosis ≤ 7 mm in diameter, ≤ 5 cm in length, not involving ≥ 2 veins, and assessed by the investigator as having no risk of thrombus progression\], and pulmonary embolism, etc.
• A history of (non-infectious) pneumonitis/interstitial lung disease requiring corticosteroid therapy; or current diagnosis of non-infectious pneumonitis/interstitial lung disease; or hospitalization for any active infection or receipt of therapeutic antibiotics within 4 weeks prior to the start of study treatment, including but not limited to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
• Prior receipt of anti-HER2 antibody-drug conjugate (ADC) therapy.
• Receipt of any anticancer therapy (including chemotherapy, targeted therapy, immunotherapy, etc.) or any other investigational drug therapy within 4 weeks or 5 half-lives prior to the first dose of this study, whichever is shorter.
• Vaccination with live-attenuated vaccines within 28 days prior to the start of study treatment, or inactivated vaccines within 7 days prior; or planned vaccination during the study period.

Other illness

• A history of other malignant tumors within 3 years prior to the first dose, or concurrent malignant tumors at screening. Subjects are eligible for enrollment if they meet one of the following two conditions:
  • Other malignant tumors treated with curative intent via a single surgical procedure, with disease-free survival (DFS) maintained for 5 consecutive years;
  • A history of cured carcinoma in situ of the cervix, non-melanoma skin cancer, or superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading the basement membrane)\].
• Presence of diseases that affect intravenous injection or venous blood collection, or factors that impair oral drug administration (e.g., dysphagia, chronic diarrhea, intestinal obstruction, etc.).
• Presence of major cardiovascular diseases.
• A history of decompensated liver cirrhosis or hepatic encephalopathy.
• Subjects with active chronic hepatitis B or active chronic hepatitis C. Subjects positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody at screening must undergo additional testing for Hepatitis B Virus (HBV) DNA titer or HCV RNA quantification.
• Active syphilis infection requiring treatment.
• Active or uncontrolled severe infection (≥ Grade 2 infection per CTCAE v5.0).
• A history of psychoactive substance abuse with inability to abstain, or presence of mental disorders.
• A history of immunodeficiency, including HIV positivity, other acquired or congenital immunodeficiency diseases, or a history of organ transplantation.
• Known hypersensitivity or allergic reaction to any study drug or its excipients.
• Any other condition judged by the investigator to pose a serious risk to subject safety or interfere with the subject's completion of the study.

Lab values

• Failure of adverse reactions from prior treatments to resolve to ≤ Grade 1 per CTCAE v5.0, with the following exceptions: Grade 2 alopecia, Grade 2 peripheral neurotoxicity, Grade 2 anemia, non-clinically significant and asymptomatic laboratory abnormalities, type 1 diabetes mellitus and hypothyroidism stabilized with hormone replacement therapy, and other toxicities judged by the investigator to pose no safety risks.

Other

• Tumor-related symptoms and treatments.
• Pregnant or lactating subjects.

• The subject voluntarily participates in this study, signs the informed consent form, and has good compliance.
• Aged 18 to 75 years old (calculated as of the date of signing the informed consent form).
• Subjects with histologically or cytologically confirmed advanced colorectal cancer.
• The subject has confirmed HER2 IHC3+ status in tumor tissue, as determined by the central laboratory designated by the sponsor.
• The subject must provide a sufficient quantity of qualified tumor specimens (fresh or archived samples collected within the past 3 years from primary or metastatic lesions) for central laboratory testing of HER2 status.
• Advanced colorectal cancer that has progressed on or been intolerant to at least 2 prior lines of standard therapy (defined as disease progression or intolerable toxicity during or within 3 months after the last standard therapy).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Expected survival of greater than 12 weeks.
• Presence of at least one measurable lesion as confirmed by RECIST 1.1 criteria.
• Laboratory tests must meet criteria
• Women of childbearing potential must agree to use effective contraception during the study and for 6 months after the study ends, and have a negative serum or urine pregnancy test within 7 days prior to study entry. Men must agree to use effective contraception during the study and for 6 months after the study ends.