Triple Negative Breast Cancer(TNBC)
Conditions
Brief summary
This multicenter, randomized, double-blind study will evaluate the safety and efficacy of PM8002 in combination with Nab-Paclitaxel compared with placebo combined with Nab-Paclitaxel as first-line treatment in inoperable locally advanced/metastatic triple-negative breast cancer(TNBC)
Interventions
DRUGPM8002
PM8002 20 mg/kg via intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle
DRUGNab-Paclitaxel
Nab-Paclitaxel 100mg/m2 via IV infusion on Days 1, 8, and 15 of each 28-day cycle
DRUGPlacebo
Placebo 20 mg/kg via IV infusion on Days 1 and 15 of each 28-day cycle
Sponsors
Biotheus Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Ability to understand and willing to provide written informed consent and to comply with scheduled visits and study procedures; * Female, aged 18 to 70 years (inclusive); * Histologically confirmed unresectable locally advanced or metastatic breast cancer with negative status for ER, PR, and HER-2. Testing results for all three markers conducted within 24 months prior to the initiation of the study by a local facility accredited by clinical research center are acceptable. If deemed necessary by the investigator during screening, subjects may provide additional biopsy to confirm the latest pathological; * Subjects who have not received prior systemic treatment（except endocrine therapy） for advanced breast cancer are eligible for the study. Subjects who have received Taxane-based chemotherapy during the neoadjuvant and/or adjuvant treatment phase are eligible, as long as the occurrence of relapse or metastasis is at least 12 months after the end of treatment; * Performance status as assessed by the Eastern Cooperative Oncology Group (ECOG) is 0-1; * Life expectancy of 12 weeks or more; * According to RECIST 1.1, the subject has at least 1 measurable lesion as the targeted lesion (the only bone metastasis or the only central nervous system metastasis should not be considered as a measurable lesion. A measurable lesion located at the previously irradiated radiation field or other local treatment area should not be selected as targeted lesion, unless the lesion shows unequivocal radiographic progression).
Exclusion criteria
* Previous treatment with immune checkpoint agonists (such as CD137 agonists) or immune checkpoint inhibitors (such as CTLA-4, PD-1, PD-L1, LAG3 monoclonal antibody, etc.) or anti-vascular endothelial growth factor (VEGF) target drugs; * Has uncontrolled or symptomatic brain or spine cord metastases; * Those who have had other active malignant tumors within 5 years prior to the study treatment, except for those that can be treated locally and have been cured ; * Poorly controlled hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg); * With a history of hypertensive crisis or hypertensive encephalopathy; * With a history of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess within the last 6 months prior to the start of the study treatment; * Adverse events resulting from prior anti-tumor therapies should be assessed and graded according to the CTCAE 5.0 criteria, subjects whose AEs have not returned to Grade 1 or below; * Has uncontrollable pleural, pericardial, or abdominal effusions; * Has received allogeneic hematopoietic stem cell transplantation or organ transplantation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) assessed by Blinded Independent Review Committee (BIRC) | Up to approximately 37 months from first patient in | Progression-free survival is defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on assessments by Blinded Independent Review Committee (BIRC) 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. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. |
| Overall Survival (OS) | Up to approximately 37 months from first patient in | Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis are censored at the date of the last follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) assessed by BIRC or investigators | Up to approximately 37 months from first patient in | DCR is defined as the sum rate of CR, PR and Stable Disease (SD), as determined by BIRC or investigators using RECIST v1.1 |
| Duration of response (DoR) assessed by BIRC or investigators | Up to approximately 37 months from first patient in | DoR is defined as the time period from the date of initial CR or PR until the date of PD or death due to any cause, whichever occurs first. |
| PFS assessed by investigator | Up to approximately 37 months from first patient in | Progression-free survival is defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by investigator 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. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. |
| Differences in the scores of health-related quality of life (HRQol) evaluated by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) | Up to 30 days after last treatment | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions How would you rate your overall health during the past week? (Item 29) and How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented. |
| Differences in the scores of health-related quality of life (HRQol) evaluated by EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR42) | Up to 30 days after last treatment | Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. |
| Incidence and severity of Adverse Event (AE) according to CTCAE 5.0 | Up to 30 days after last treatment | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Objective response rate (ORR) assessed by BIRC or investigators | Up to approximately 37 months from first patient in | ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced a CR or PR as assessed by BIRC or investigators based on RECIST 1.1 is presented. |
Countries
China
Contacts
Primary ContactYanqing Cao
Backup ContactLinlin Fan
Outcome results
None listed