Status and phase
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About
The purpose of this study is to assess the efficacy and safety of Cadonilimab (AK104) combined with chemotherapy and bevacizumab as first-line treatment for patients with RAS mutated or right sided-metastatic MSS colorectal cancer
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Able to understand and voluntarily sign a written informed consent form, which must be signed before the designated research procedures required for the study are carried out.
Age at the time of signing the Informed Consent Form (ICF) is ≥ 18 years old and ≤ 75 years old, both male and female.
The Eastern Cancer Collaborative Organization (ECOG) has a physical fitness score of 0 or 1.
The expected survival period is ≥ 3 months.
Recurrent or incurable metastatic colorectal adenocarcinoma confirmed by Histopathology.(UICC/AJCC colorectal TNM stage System (8th edition 2017))
Genetic testing revealed RAS (including KRAS and NRAS) mutations, or primary sites located in the right half of the colon (including cecum, rising Colon and proximal 2/3 transverse colon).
Did not receive systemic treatment for recurrent or metastatic disease.
According to the RECIST v1.1 standard, there is at least one measurable tumor lesion. Agree to provide archived or freshly obtained tumor tissue samples (formalin fixed paraffin embedded [FFPE] tissue wax blocks or at least 5 unstained tumor tissue slice samples) to confirm PD-L1 expression.
The time interval between the end of adjuvant therapy was >12 months.
Having good organ function:
Blood routine examination (no blood components or cell growth factors were used to support treatment within the first 7 days of randomization):
Kidney:
Creatinine<1.5 × ULN, or creatinine clearance rate * (CrCl) calculated value ≥ 50mL/min;
*The Cockcroft Fault formula will be used to calculate CrCl: CrCL (mL/min)={(140 age) × Body weight (kg) × F} /(SCr (mg/dL) × 72) Among them: F=1 for males and F=0.85 for females; SCr=serum creatinine. Urinary protein<2+or 24-hour urine protein quantification<1.0g.
Liver:
Serum total bilirubin (TBiL) ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN (AST and ALT ≤ 5 for subjects with liver metastasis) × ULN, but not accompanied by elevated bilirubin);
Coagulation function:
International standardized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN
Thyroid function: thyroid stimulating hormone (TSH) ≤ ULN; If abnormal, T3 and T4 levels should be investigated, and normal levels Can be selected
Female subjects with fertility must undergo a serum pregnancy test within 72 hours before the first medication, and the result should be negative. If a female subject with fertility engages in sexual activity with an unsterilized male partner, the subject must adopt an acceptable contraceptive method starting from screening and must agree to continue using the contraceptive method for 120 days after the last dose of the study drug; Periodic abstinence and safe period contraception are unacceptable contraceptive methods. Whether to stop contraception after this time point should be discussed with researchers.
Exclusion criteria
Previously received treatment with PD-1 monoclonal antibody, PD-L1 monoclonal antibody, or CTLA-4 monoclonal antibody.
The tumor tissue was found to be dMMR or MSI-H
Received palliative local treatment within the first 2 weeks of randomization; Received systemic non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, etc.) within the first 2 weeks of randomization; In the first 2 weeks of randomization, they received Chinese herbal medicine or traditional Chinese patent medicines and simple preparations with anti-tumor indications.
Currently participating in another clinical study, unless it is an observational, non-interventional clinical study, or a follow-up period of an intervention study.
Had or was currently present with other malignancies within the first 3 years of randomization. The following conditions can be included: cured uterus cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (cancer in situ) and T1 (tumor infiltrating basal membrane)].
Have active or untreated brain metastases, meningeal metastases, spinal cord compression, or leptomeningeal diseases. However, participants who meet the following requirements and have measurable lesions outside the central nervous system are allowed to be enrolled: asymptomatic after treatment, imageologically stable for at least 4 weeks before the start of study treatment (if there are no new or expanded brain metastases), and have stopped systemic glucocorticoid and anticonvulsant drug treatment for at least 2 weeks.
Have clinical symptoms of pleural effusion, pericardial effusion, or pleural/ascites that require frequent drainage (≥ once per month).
Active autoimmune diseases that require systematic treatment within the first 2 years of randomization, or autoimmune diseases that the researcher determines may recur or plan treatment. Except for the following:
Any of the following cardiovascular or cerebrovascular diseases or risk factors:
Toxicity that has not been alleviated by previous anti-tumor therapy is defined as failure to regress to the National Cancer Institute Adverse Event General Terminology Standard ((NCICTCAE v5.0) level 0 or 1, or the level specified in the inclusion/exclusion criteria, except for hair loss/pigmentation, ≥ Level 2 peripheral nerve disease).
The presence of interstitial lung disease or non infectious pneumonia is known, and the disease is currently symptomatic or requires systemic glucocorticoid treatment in the past. Researchers have determined that it may affect the toxicity assessment or management related to the study treatment.
Active pulmonary tuberculosis is known to exist. Subjects suspected of active pulmonary tuberculosis need to undergo chest X-ray examination, sputum examination, and elimination through clinical symptoms and signs.
Received systemic anti infective therapy (excluding antiviral therapy for hepatitis B or C) within the first 2 weeks of randomization.
Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
Imaging (CT or MRI) shows that the tumor has invaded the large blood vessels or is not clearly delimited from the blood vessels.
Have clinical active diverticulitis, abdominal abscess, and gastrointestinal obstruction, unhealed wounds, ulcers, or fractures.
Clinically significant bleeding symptoms or bleeding tendencies within the first month of randomization, such as gastrointestinal bleeding, active hemoptysis, or bleeding, clotting disease are taking warfarin, aspirin, or other antiplatelet drugs (except maintenance doses: aspirin ≤100mg/ day, clopidogrel ≤75mg/ day), or regardless of severity，Subjects with any signs of bleeding or medical history that the investigator has determined are not suitable for enrollment.
Received major surgical treatment, open biopsy, or significant traumatic injury (except needle biopsy or gastroenteroscopic tissue biopsy) within the first 28 days of randomization.
Individuals with a known history of immune deficiency or HIV testing positive,Known active syphilis infection.
Subjects who require systemic treatment with glucocorticoids (>10mg/day prednisone or equivalent dose) or other immunosuppressive drugs within the first 14 days of randomization. Except for the following:
For untreated active hepatitis B subjects (HBsAg positive and HBV-DNA more than 1000 copies/ml [200IU/ml] or higher than the lower detection limit), patients with hepatitis B are required to receive anti hepatitis B virus treatment during the study treatment period; Active hepatitis C subjects (with positive HCV antibodies and HCV-RNA levels above the detection limit).
Received live vaccine within 30 days prior to randomization, or planned to receive live vaccine during the study period.
Subjects who have a known history of allergic or hypersensitive reactions to Cadonilimab, bevacizumab, capecitabine, oxaliplatin or any of their components. A history of severe hypersensitivity to other monoclonal antibodies is known.
In the judgment of the investigator, there is a concomitant disease that seriously endangers the safety of the subjects or interferes with the completion of the study, or subjects who were not suitable for inclusion for other reasons.
Primary purpose
Allocation
Interventional model
Masking
30 participants in 1 patient group
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Central trial contact
Caigang Liu, MD; Nan Niu, MD
Data sourced from clinicaltrials.gov
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