Trial Title:
Study of Cadonilimab (AK104) Plus Eribulin vs. Eribulin Monotherapy for Recurrent or Metastatic Triple-negative Breast Cancer
NCT ID:
NCT06202313
Condition:
Triple Negative Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Cadonilimab
Description:
Participants receive Cadonilimab 10mg/kg IV on Day 1 of each 21-day cycle PLUS Eribulin
1.4mg/m^2 IV on Days 1 and 8 of each 21-day cycle.
Arm group label:
Cadonilimab + Eribulin
Other name:
AK104
Intervention type:
Drug
Intervention name:
Eribulin
Description:
Participants receive Eribulin 1.4mg/m^2 IV on Days 1 and 8 of each 21-day cycle.
Arm group label:
Cadonilimab + Eribulin
Arm group label:
Eribulin
Summary:
The purpose of this study is to assess the efficacy and safety of Cadonilimab (AK104)
plus Eribulin compared to the efficacy and safety of Eribulin monotherapy in the
treatment of adult patients with recurrent, or metastatic triple negative breast cancer.
The primary study hypothes is that the combination of Cadonilimab (AK104) plus Eribulin
is superior to Eribulin monotherapy with respect to Progression-free Survival (PFS) per
Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by the
Investigator.
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 metastatic incurable triple negative breast cancer confirmed by
histology and/or cytology.
6. Having received ≤ 2-line systematic treatment for recurrent or metastatic diseases,
including: ① untreated after recurrence or metastasis, but receiving paclitaxel and
anthracycline drugs within 12 months before recurrence or metastasis (including
neoadjuvant treatment stage and adjuvant treatment stage), Or ② After recurrence or
metastasis, the subject has received 1-2 lines of treatment (including at least one
anthracycline and one paclitaxel in the previous adjuvant treatment stage,
neoadjuvant treatment stage, or treatment after recurrence/metastasis).
7. 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.
8. The time interval between the last treatment: (a) If the last treatment is targeted
therapy such as Olaparib, the interval should be ≥ 2 weeks; (b) If the last
treatment is chemotherapy, an interval of ≥ 4 weeks is required.
9. Having good organ function:
1. Blood routine examination (no blood components or cell growth factors were used
to support treatment within the first 2 weeks 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); Serum albumin (ALB) ≥ 28g/L.
4. Coagulation function:
International standardized ratio (INR) and activated partial thromboplastin time
(APTT) ≤ 1.5 × ULN
10. 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. human epidermal growth factor receptor 2 (HER2) is positive and/or hormone receptor
is positive.
2. Previously received treatment with PD-1 monoclonal antibody, PD-L1 monoclonal
antibody, or CTLA-4 monoclonal antibody.
3. Received systematic anti-tumor therapy within the first 4 weeks of randomization,
including chemotherapy, radiation therapy, immunotherapy, targeted therapy (small
molecule targeted therapy within the first 2 weeks of randomization), biological
agent therapy, etc; 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. 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.
6. Have clinical symptoms of pleural effusion, pericardial effusion, or pleural/ascites
that require frequent drainage (≥ once per month).
7. 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.
8. 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. Previous history of myocarditis and cardiomyopathy.
5. Left ventricular ejection fraction (LVEF)<50%.
9. 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. Subjects who have
experienced ≥ 3 levels of immune related toxicity during previous treatment with
immune checkpoint inhibitors are not allowed to be enrolled.
For subjects who experience irreversible toxicity and are expected to not worsen
after administration of the study drug (such as hearing loss), they may be included
in the study after consultation with the medical supervisor. It is known that there
are 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. Subjects with long-term toxicity
that cannot be restored according to the judgment of the researchers may be included
in the study after consultation with medical inspectors.
10. According to the NCICTCAE v5.0 standard, it is defined as ≥ 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. Have clinical active hemoptysis, active diverticulitis, abdominal abscess, and
gastrointestinal obstruction.
16. Clinically significant bleeding symptoms or clear bleeding tendencies within the
first month of randomization, such as gastrointestinal bleeding, hemorrhagic gastric
ulcer, or vasculitis.
17. 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).
18. Individuals with a known history of immune deficiency or HIV testing positive.
19. 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. Received live vaccine within 30 days prior to randomization, or planned to receive
live vaccine during the study period.
22. A history of severe hypersensitivity to other monoclonal antibodies is known.
23. Subjects who have a known history of allergic or hypersensitive reactions to
cardunizumab, iribrin, or any of their components.
Gender:
Female
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shengjing Hospital of China Medical University
Address:
City:
Shenyang
Zip:
110004
Country:
China
Contact:
Last name:
Nan Niu, Phd
Phone:
+8618940256668
Email:
niunannancy@163.com
Start date:
February 10, 2024
Completion date:
December 30, 2028
Lead sponsor:
Agency:
Shengjing Hospital
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/NCT06202313
