Triple Negative Breast Cancer
Conditions
Brief 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.
Interventions
BIOLOGICALCadonilimab
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.
DRUGEribulin
Participants receive Eribulin 1.4mg/m\^2 IV on Days 1 and 8 of each 21-day cycle.
Sponsors
Shengjing Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator | Up to approximately 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator | Up to approximately 1 year | ORR is defined as the percentage of the participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters). |
| Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator | Up to approximately 1 year | For participants who demonstrate CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR per RECIST 1.1 as assessed by Investigator will be presented. |
| Overall Survival (OS) | Up to approximately 2 years | OS is defined as the time from randomization to death due to any cause. |
| Number of Participants Who Experience a Serious AE (SAE) | From randomization through 90 days after last dose of study treatment | An SAE is defined as any untoward medical occurrence that, at any dose: a.) Results in death; b.) Is life-threatening; c.) Requires inpatient hospitalization or prolongation of existing hospitalization; d.) Results in persistent or significant disability/incapacity; e.) Is a congenital anomaly/birth defect; f.) Other important medical events; h.) Is a new cancer (that is not a condition of the study) or i.) Is associated with an overdose. The number of participants who experience an SAE will be presented. |
| Number of Participants Who Experience an Immune-related AE (irAE) | From randomization through 90 days after last dose of study treatment for serious irAEs | AEs associated with Cadonilimab exposure may be a result of an immune response. These irAEs may occur shortly after the first dose or several months after the last dose of Cadonilimab treatment and may affect more than one body system simultaneously. For this study irAEs include, but are not limited to: Pneumonitis; Diarrhea/Colitis; Aspartate transaminase (AST)/Alanine transaminase (ALT) elevation or Increased bilirubin; Type 1 diabetes mellitus or Hyperglycemia; Hypophysitis; Hyperthyroidism; Hypothyroidism; Nephritis and Renal dysfunction; and Myocarditis. The number of participants who experience an irAE will be presented. |
| Number of Participants Who Experience an Adverse Event (AE) | From randomization through 30 days after last dose of study treatment | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be presented. |
Countries
China
Contacts
Primary ContactNan Niu
Outcome results
None listed