Cadonilimab (AK104) Combined With Chemotherapy and Bevacizumab as First-line Treatment for RAS Mutated or Right Sided-metastatic MSS Colorectal Cancer

NCT06566755 | Recruiting Phase 3

• 1 other identifier: AK104-IIT-C-M-0020
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator

  PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator will be presented.

  Up to approximately 1 year

Secondary Outcomes (7)

• Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator

  Up to approximately 1years

• Disease control Rate (DCR) Per RECIST 1.1 as Assessed by Investigator

  Up to approximately 1 year

• Duration of Response (DoR) Per RECIST 1.1 as Assessed by Investigator

  Up to approximately 1 year

• Time to response（TTR）

  Up to approximately 6 months

• Overall Survival (OS)

  From randomization through 90 days after last dose of study treatment

Study Arms (1)

Cadonilimab (AK104) combined with chemotherapy and bevacizumab

EXPERIMENTAL

Participants receive Cadonilimab PLUS chemotherapy and bevacizumab of each 21-day cycle. Treatment period (4-8 cycles)： * Cadonilimab: 10mg/kg, intravenous infusion, D1, Q3W; * CapeOx chemotherapy regimen Q3W+ bevacizumab, Q3W: oxaliplatin: 130 mg/m2 intravenous infusion, D1, Q3W capecitabine: 850 mg/m2 orally, D1-14, Q3W, twice daily; bevacizumab injection: 7.5mg/kg, IV, D1, Q3W. Maintenance treatment period： * Cadonilimab: 10mg/kg, administered D1, Q3W; * capecitabine: 1000 mg/m2 orally, D1-14, Q3W, twice daily; * bevacizumab injection: 7.5mg/kg, IV, D1, Q3W.

Drug: Cadonilimab (AK104) combined with chemotherapy and bevacizumab

Interventions

Cadonilimab (AK104) combined with chemotherapy and bevacizumab DRUG

Participants receive Cadonilimab PLUS chemotherapy and bevacizumab of each 21-day cycle. Treatment period (4-8 cycles)： * Cadonilimab: 10mg/kg, intravenous infusion, D1, Q3W; * CapeOx chemotherapy regimen Q3W+ bevacizumab, Q3W: oxaliplatin: 130 mg/m2 intravenous infusion, D1, Q3W; capecitabine: 850 mg/m2 orally, D1-14, Q3W, twice daily; bevacizumab injection: 7.5mg/kg, IV, D1, Q3W. Maintenance treatment period： * Cadonilimab: 10mg/kg, administered D1, Q3W; * capecitabine: 1000 mg/m2 orally, D1-14, Q3W, twice daily; * bevacizumab injection: 7.5mg/kg, IV, D1, Q3W.

Cadonilimab (AK104) combined with chemotherapy and bevacizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L;
• Platelet count ≥ 100 × 10\^9/L;
• Hemoglobin ≥ 9.0g/dL.
• Kidney:

You may not qualify if:

• 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:
• Skin diseases that do not require systematic treatment (such as vitiligo, alopecia, psoriasis, or eczema);
• Hypothyroidism caused by autoimmune thyroiditis requires only stable doses of hormone replacement therapy;
• Type I diabetes requiring only a stable dose of insulin replacement therapy;
• Childhood asthma has completely relieved, and no intervention is required in adulthood;
• Researchers have determined that the disease will not recur without external triggering factors.
• Any of the following cardiovascular or cerebrovascular diseases or risk factors:
• Myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, acute or persistent myocardial ischemia, symptomatic heart failure (grade 2 or above according to the New York Heart Association functional classification), symptomatic or poorly controlled arrhythmia, or any arterial thromboembolism event occurred within the first 6 months of randomization.

Sponsors & Collaborators

• Caigang Liu: lead

Study Sites (1)

Shengjing Hospital of China Medical University

Shenyang, Liaoning, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Drug Therapy; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Nan Niu, MD

CONTACT

86+18940256668; niunannancy@163.com

Caigang Liu, MD

CONTACT

86+18940256668; niunannancy@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: August 21, 2024
• First Posted: August 22, 2024
• Study Start: February 1, 2024
• Primary Completion: February 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: August 22, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)