Antibody-drug Conjugates, HER2, mCRC, Targeted Therapy
Conditions
Keywords
SHR-1811, mCRC, second-line
Brief summary
A randomized, controlled, multicenter clinical study of SHR-A1811 combined with bevacizumab for the second-line treatment of metastatic colorectal cancer
Interventions
HER2 ADC
FOLFIRI+BEV
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Intervention model description
SHR-A1811 combined with bevacizumab; chemotherapy combined with bevacizumab
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
-Provide a written informed consent form to voluntarily participate in this study. Male or female subjects aged 18-75 years. * Patients with histologically or cytologically confirmed recurrent or metastatic colorectal adenocarcinoma that is not amenable to curative resection. * Patients who have experienced disease progression following first-line standard therapy with oxaliplatin combined with fluoropyrimidine-based drugs. * Patients with disease progression within 12 months after completion of neoadjuvant or adjuvant therapy are eligible for inclusion. * Patients who have previously received irinotecan as part of first-line therapy may be included if investigators from the leading center determine through discussion that the patient is likely to benefit from treatment in the control group. * HER2 expression status: Includes patients with HER2 overexpression (IHC 3+ / IHC 2+ with FISH positivity) or HER2 low-to-moderate expression (IHC 2+ with FISH negativity or IHC 1+). * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1. * Ability to provide a report documenting RAS/BRAF gene status. * Expected survival time of at least 6 months. * Presence of radiologically assessed measurable lesions at baseline (per RECIST 1.1 criteria). Measurable lesions should not have received prior local therapy such as radiotherapy. Lesions located within previously irradiated areas may be selected as target lesions if disease progression in these lesions is confirmed. * Adequate function of major organs, meeting the following requirements (administration of blood components or cell growth factors for corrective treatment is not allowed within 14 days prior to the first dose of study medication): * Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L Platelet count ≥ 100 × 10⁹/L Hemoglobin ≥ 90 g/L Serum albumin ≥ 30 g/L Total bilirubin ≤ 1.5 × Upper Limit of Normal (ULN) Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 × ULN; for patients with liver metastases, ALT and AST ≤ 5 × ULN Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate \> 60 mL/min (calculated by the Cockcroft-Gault formula) Activated Partial Thromboplastin Time (APTT) and International Normalized Ratio (INR) ≤ 1.5 × ULN. Patients receiving stable-dose anticoagulant therapy (e.g., low-molecular-weight heparin or warfarin) with INR within the expected therapeutic range for anticoagulants are eligible for screening. * For female subjects of childbearing potential: A negative serum pregnancy test result is required within 3 days prior to the first dose, and the subject must not be breastfeeding. Must agree to use effective contraceptive measures during the study period and for at least 7 months after the last dose of SHR-A1811, or for at least 6 months after the last dose of other study medications. -For male subjects whose partners are of childbearing potential: The subject must have undergone surgical sterilization, or agree to use effective contraceptive measures during the study period and for at least 7 months after the last dose of SHR-A1811, or for at least 6 months after the last dose of other study medications. Sperm donation is prohibited during the study period.
Exclusion criteria
* Toxicities from prior anti-tumor therapies have not resolved to ≤ Grade 1 per the CTCAE v5.0 criteria (except for toxicities deemed to pose no safety risk by the investigator, e.g., alopecia) or to the levels specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | The end of cycle 2 (each cycle is 21 days) for SHR-A1811+BEV group and the end of cycle 3 (each cycle is 14 days) for FOLFIRI+BEV group | objective response rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months | progression free survival |
| OS | From data of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months | overall survival |
Outcome results
None listed