CRC (Colorectal Cancer)
Conditions
Brief summary
Efficacy and safety of retlirafusp alfa combined with bevacizumab and chemotherapy with or without short-course radiotherapy in conversion therapy for advanced colorectal cancer liver metastases: an exploratory study.
Interventions
RADIATIONSCRT
short-course radiotherapy
Retlirafusp alfa :1800 mg via intravenous infusion every 3 weeks (q3w)
DRUGBevacizumab
Bevacizumab: 7.5 mg/kg, D1, IV, Q3W
DRUGCAPOX
CAPOX:oxaliplatin 130 mg/m²,IV, D1 ; Capecitabine: 1000 mg/m² orally twice daily, Days 1-14; Cycle duration: 3 weeks per cycle
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Provide signed written informed consent and voluntarily agree to participate in this study. 2. Age ≥ 18 years and ≤ 75 years. 3. Histologically confirmed colorectal adenocarcinoma. 4. Liver metastasis confirmed by imaging or pathology. 5. Have not received any prior anti-cancer therapy. 6. At least one measurable lesion according to RECIST v1.1. 7. pMMR/MSS status confirmed by a local testing center, or unknown status. 8. Be able to swallow tablets. 9. ECOG PS 0-1 10. Have no contraindications for surgery. 11. Have adequate major organ function.
Exclusion criteria
1. Have a history of allergy to monoclonal antibodies, any component of retlirafusp alfa, bevacizumab, capecitabine, oxaliplatin, or other platinum-based agents. 2. Have previously received or are currently receiving any of the following treatments: 1. Any anti-tumor therapy including surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy. 2. Use of immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes within 2 weeks prior to the first dose of study drug (at a dose \> 10 mg/day prednisone or equivalent). Inhaled or topical corticosteroids, and adrenal replacement therapy at doses \> 10 mg/day prednisone or equivalent, are permitted in the absence of active autoimmune disease. 3. Receipt of live attenuated vaccine within 4 weeks prior to the first dose of study drug. 4. Major surgery or severe trauma within 4 weeks prior to the first dose of study drug. 3. Have any active autoimmune disease or history of autoimmune disease, including but not limited to interstitial pneumonitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism (patients on hormone replacement therapy may be considered for inclusion). Patients with psoriasis or childhood asthma/allergy that has completely resolved and requires no intervention in adulthood may be considered for inclusion, but those requiring medical intervention with bronchodilators are not eligible. 4. Have a history of immunodeficiency, including HIV-positive test, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation. 5. Have poorly controlled cardiac symptoms or diseases, including but not limited to: (1) heart failure of New York Heart Association (NYHA) class ≥ II; (2) unstable angina; (3) myocardial infarction within 1 year; (4) clinically significant supraventricular or ventricular arrhythmias that have not been clinically intervened or remain poorly controlled after intervention. 6. Have experienced a severe infection (CTCAE grade \> 2) within 4 weeks prior to the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, or infectious complications; or have evidence of active pulmonary inflammation on baseline chest imaging, or have signs/symptoms of infection or require oral or intravenous antibiotic therapy within 14 days prior to the first dose of study drug (except for prophylactic antibiotic use). 7. Have active pulmonary tuberculosis infection by history or CT examination, or a history of active pulmonary tuberculosis infection within 1 year prior to enrollment, or a history of active pulmonary tuberculosis infection \> 1 year ago without adequate treatment. 8. Have hepatitis B (HBV DNA ≥ 2000 IU/mL or ≥ 10⁴ copies/mL), or hepatitis C (positive anti-HCV antibody and HCV RNA above the lower limit of detection of the assay). 9. Have been diagnosed with another malignancy within 5 years prior to the first dose of study drug, except for malignancies with a low risk of metastasis or death (5-year survival rate \> 90%), such as adequately treated basal cell carcinoma or squamous cell skin cancer, or cervical carcinoma in situ, which may be considered for inclusion. 10. Are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | Each follow up visit, assessed up to 60 months | Assessed by the investigator using RECIST v1.1, defined as the time from the start of study treatment to disease progression, or relapse after resection of liver metastases, or death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | assessed up to 12 months | Partial response (PR) plus complete response (CR)): assessed by the investigator using RECIST v1.1 criteria |
| R0 Resection Rate | Each follow up visit, assessed up to 12 month | Defined as the proportion of patients who achieve complete resection after treatment |
| Pathological complete response rate (pCR) | 2 years after last patient in study | Pathological complete response rate (pCR) of the resected lesions |
| Overall Survival | Each follow up visit, assessed up to 60 months | Defined as the time from the start of study treatment to death due to any cause |
| Toxicity (AE) | 2 years after last patient in study | Patients will be evaluated for Adverse Events at the start of each treatment cycle according to CTCAE version 6.0. |
Countries
China
Contacts
CONTACTZhenyu Lin, MD
PRINCIPAL_INVESTIGATORTao Zhang, MD
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
PRINCIPAL_INVESTIGATORKaixiong Tao, MD
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed