Trial Title:
Cadonilimab (AK104) Combined With Chemotherapy and Bevacizumab as First-line Treatment for RAS Mutated or Right Sided-metastatic MSS Colorectal Cancer
NCT ID:
NCT06566755
Condition:
Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Bevacizumab
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cadonilimab (AK104) combined with chemotherapy and bevacizumab
Description:
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.
Arm group label:
Cadonilimab (AK104) combined with chemotherapy and bevacizumab
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
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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.
2. Age at the time of signing the Informed Consent Form (ICF) is ≥ 18 years old and ≤
75 years old, both male and female.
3. The Eastern Cancer Collaborative Organization (ECOG) has a physical fitness score of
0 or 1.
4. The expected survival period is ≥ 3 months.
5. Recurrent or incurable metastatic colorectal adenocarcinoma confirmed by
Histopathology.(UICC/AJCC colorectal TNM stage System (8th edition 2017))
6. 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).
7. Did not receive systemic treatment for recurrent or metastatic disease.
8. 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.
9. The time interval between the end of adjuvant therapy was >12 months.
10. Having good organ function:
1. 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.
2. 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.
3. 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);
4. Coagulation function:
International standardized ratio (INR) and activated partial thromboplastin
time (APTT) ≤ 1.5 × ULN
5. Thyroid function: thyroid stimulating hormone (TSH) ≤ ULN; If abnormal, T3 and
T4 levels should be investigated, and normal levels Can be selected
11. 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.
1. Women with fertility refer to those who have not undergone surgical
sterilization (i.e. bilateral fallopian tube ligation, bilateral oophorectomy,
or total hysterectomy) or those who have not undergone menopause (defined as
those who have ceased menstruation for at least 12 consecutive months without
alternative medical reasons, and whose serum follicle stimulating hormone
levels are within the laboratory reference range of postmenopausal women);
2. An efficient contraceptive method refers to a contraceptive method with a low
failure rate (such as less than 1% per year) under continuous and correct use.
Not all contraceptive methods are efficient. In addition to barrier
contraception, female subjects with fertility can also use hormonal
contraception (such as birth control pills), intrauterine device contraception,
etc. to ensure that pregnancy does not occur.
Exclusion Criteria:
1. Previously received treatment with PD-1 monoclonal antibody, PD-L1 monoclonal
antibody, or CTLA-4 monoclonal antibody.
2. The tumor tissue was found to be dMMR or MSI-H
3. 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.
4. Currently participating in another clinical study, unless it is an observational,
non-interventional clinical study, or a follow-up period of an intervention study.
5. 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)].
6. 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.
7. Have clinical symptoms of pleural effusion, pericardial effusion, or pleural/ascites
that require frequent drainage (≥ once per month).
8. 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:
1. Skin diseases that do not require systematic treatment (such as vitiligo,
alopecia, psoriasis, or eczema);
2. Hypothyroidism caused by autoimmune thyroiditis requires only stable doses of
hormone replacement therapy;
3. Type I diabetes requiring only a stable dose of insulin replacement therapy;
4. Childhood asthma has completely relieved, and no intervention is required in
adulthood;
5. Researchers have determined that the disease will not recur without external
triggering factors.
9. Any of the following cardiovascular or cerebrovascular diseases or risk factors:
1. 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.
2. A history of deep vein thrombosis, pulmonary embolism, or other severe
thromboembolism within the first 3 months of randomization.
3. Have major vascular diseases such as aortic aneurysm, aortic dissection
aneurysm, internal carotid artery stenosis that may endanger life or require
surgery within 6 months.
4. Uncontrolled hypertension (systolic blood pressure ≥150mmHg or diastolic blood
pressure ≥100mmHg after standard antihypertensive therapy)
5. Previous history of myocarditis and cardiomyopathy.
6. Left ventricular ejection fraction (LVEF)<50%.
10. 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).
11. 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.
12. 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.
13. Received systemic anti infective therapy (excluding antiviral therapy for hepatitis
B or C) within the first 2 weeks of randomization.
14. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation.
15. Imaging (CT or MRI) shows that the tumor has invaded the large blood vessels or is
not clearly delimited from the blood vessels.
16. Have clinical active diverticulitis, abdominal abscess, and gastrointestinal
obstruction, unhealed wounds, ulcers, or fractures.
17. 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.
18. Received major surgical treatment, open biopsy, or significant traumatic injury
(except needle biopsy or gastroenteroscopic tissue biopsy) within the first 28 days
of randomization.
19. Individuals with a known history of immune deficiency or HIV testing positive,Known
active syphilis infection.
20. 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:
1. If there is no active autoimmune disease, it is allowed to use inhaled,
ophthalmic, or topical corticosteroids or other corticosteroids with a dose ≤
10mg/day of prednisone or equivalent.
2. The dosage of systemic glucocorticoids in physiological doses is ≤ 10mg/day of
prednisone or equivalent doses of other glucocorticoids.
3. Glucocorticoids are used as pretreatment for infusion related reactions or
allergic reactions (such as medication before CT examination).
21. 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).
22. Received live vaccine within 30 days prior to randomization, or planned to receive
live vaccine during the study period.
23. 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.
24. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shengjing Hospital of China Medical University
Address:
City:
Shenyang
Country:
China
Status:
Recruiting
Contact:
Last name:
Caigang Liu, MD
Phone:
86+18940256668
Email:
liucg@sj-hospital.org
Start date:
February 1, 2024
Completion date:
February 1, 2027
Lead sponsor:
Agency:
Caigang Liu
Agency class:
Other
Source:
Shengjing Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06566755
