A Phase II, Multi-site, Randomized, Open-label Clinical Trial to Evaluate the Safety, Efficacy, and Pharmacokinetics of BNT327 at Two Dose Levels in Combination With Chemotherapeutic Agents as First- and Second-line Treatment in Triple-negative Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- BNT327 Dose Level 1 (DL1)
- Conditions
- Locally Advanced Breast Cancer
- Sponsor
- BioNTech SE
- Enrollment
- 83
- Locations
- 93
- Primary Endpoint
- Occurrence of treatment emergent adverse events (TEAEs), adverse events of special interest (AESIs), treatment emergent serious adverse events (SAEs)
- Status
- Active, Not Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
This study is a Phase II, multi-site, randomized, open-label clinical study to evaluate the safety, efficacy, and pharmacokinetics (PK) of BNT327 at two dose levels in combination with chemotherapeutic agents in the first- and second-line treatment of participants with locally advanced/metastatic triple-negative breast cancer (mTNBC).
Detailed Description
Participants will be treated until disease progression, intolerable toxicity, participant withdrawal, death, study termination or up to 2 years (whichever occurs first). The study plans to randomize or assign eligible participants into two cohorts, i.e., Cohort 1 and Cohort 2. In Cohort 1, participants will be randomized to two treatment arms investigating two dose levels of BNT327 in combination with Nab-paclitaxel. Participants in Cohort 2 will be assigned to one of three treatment arms by their clinician. Cohort 2 will not begin until the appropriate dose to move forward has been determined from Cohort 1. After this, the arms in Cohort 2 exploring different chemotherapy combinations will begin to enroll. Participants in Cohort 2, Arm 1 will receive the optimal dose of BNT327 in combination with paclitaxel. Participants in Cohort 2, Arms 2 and 3, will receive the equivalent dose of BNT327 administered once every 3 weeks (Q3W) in combination with gemcitabine plus carboplatin (Arm 2), or eribulin (Arm 3).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have given informed consent by signing and dating an informed consent form before initiation of any study-specific procedures.
- •Male or female, aged ≥18 years at the time of giving informed consent.
- •Are willing and able to comply with scheduled visits, the treatment schedule, the planned study assessments (including participant completed diaries) and other requirements of the study. This includes that they are able to understand and follow study-related instructions.
- •Have confirmed locally recurrent inoperable or mTNBC as defined by the most recent American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines. Note, participants initially diagnosed with hormone receptor-positive and/or HER2-positive breast cancer must have histological confirmation of TNBC in a tumor biopsy obtained from a local recurrence or distant metastasis site.
- •Systemic treatment naïve locally advanced/metastatic participants are eligible if:
- •They have received no prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, immunotherapy, or investigational agents.
- •They have completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months has elapsed between the completion of treatment with curative intent (e.g., date of primary breast tumor surgery or date of last adjuvant chemotherapy administration, or date of last radiation therapy, whichever occurred last) and first documented local or distant disease recurrence. This also includes participants initially diagnosed with hormone receptor-positive and/or HER2-positive breast cancer prior to TNBC diagnosis.
- •Participants who received one prior systemic therapy in the locally advanced/metastatic setting are eligible if:
- •They have received one systemic chemotherapy in the metastatic setting and have progressed on first line therapy. Radiographic progression must have been documented. Radiographic progression is defined as unequivocal progression of existing tumor lesions or developing new tumor lesions as assessed by the investigator.
- •They have had a recurrence-free interval of ≥6 months if they have received treatment with curative intent in the past. A recurrence-free interval of ≥6 months is required for all participants (both first- and second-line treatment settings) who have received prior treatment for breast cancer with curative intent.
Exclusion Criteria
- •Are pregnant or breastfeeding or are planning pregnancy or planning to father children during the study or within 6 months after the last dose of IMP.
- •Have a medical, psychological, or social condition which, in the opinion of the investigator, could compromise their wellbeing if they participate in the study, or that could prevent, limit, or confound the protocol-specified assessments or procedures, or that could impact adherence to protocol described requirements.
- •Have received any of the following therapies or drugs prior to the initiation of study:
- •Participants who received prior treatment with a PD(L)-1/Vascular Endothelial Growth Factor bispecific antibody.
- •Have received a systemic anticancer regimen within 4 weeks prior to the initiation of study treatment or have received palliative radiotherapy within 7 days prior to the initiation of study treatment, or have received any other chemotherapy, curative/palliative radiotherapy, biologic therapy (including tumor vaccines, cytokines, or growth factors for tumor control) or any experimental antitumor drugs within 4 weeks prior to the initiation of study treatment.
- •Have received other systemic immunostimulatory agents or immunosuppressive therapies (such as interferon-alpha \[IFN-α\], interleukin-2 \[IL-2\], or methotrexate) within 4 weeks prior to the initiation of study treatment or are within five half-lives of the treatment drug (whichever is longer). Exception: Excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short-term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).
- •Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 3 weeks prior to the initiation of study treatment.
- •Have been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of study treatment.
- •Received broad-spectrum IV antibiotics therapy within 3 weeks prior to initiation of study treatment.
- •Use of any non-study investigational medicinal product within five half-lives of first dose or within 4 weeks, whichever is longer, before initiation of study treatment in this study or ongoing participation in the active treatment phase of another interventional clinical study.
Arms & Interventions
Cohort 1 Arm 1 - BNT327 DL1 + Nab-paclitaxel
Intervention: BNT327 Dose Level 1 (DL1)
Cohort 1 Arm 1 - BNT327 DL1 + Nab-paclitaxel
Intervention: Nab-placlitaxel
Cohort 1 Arm 2 - BNT327 DL2 + Nab-paclitaxel
Intervention: BNT327 Dose Level 1 (DL2)
Cohort 1 Arm 2 - BNT327 DL2 + Nab-paclitaxel
Intervention: Nab-placlitaxel
Cohort 2 Arm 1 - BNT327 Optimized dose + Paclitaxel
Intervention: Paclitaxel
Cohort 2 Arm 1 - BNT327 Optimized dose + Paclitaxel
Intervention: BNT327 Optimized Dose
Cohort 2 Arm 2 - BNT327 Equivalent Q3W dose + Gemcitabine + Carboplatin
Intervention: Carboplatin
Cohort 2 Arm 2 - BNT327 Equivalent Q3W dose + Gemcitabine + Carboplatin
Intervention: Gemcitabine
Cohort 2 Arm 2 - BNT327 Equivalent Q3W dose + Gemcitabine + Carboplatin
Intervention: BNT327 Equivalent Q3W Dose
Cohort 2 Arm 3 - BNT327 Equivalent Q3W dose + Eribulin
Intervention: Eribulin
Cohort 2 Arm 3 - BNT327 Equivalent Q3W dose + Eribulin
Intervention: BNT327 Equivalent Q3W Dose
Outcomes
Primary Outcomes
Occurrence of treatment emergent adverse events (TEAEs), adverse events of special interest (AESIs), treatment emergent serious adverse events (SAEs)
Time Frame: up to 100 days after the last dose of treatment
In the combination treatment regimen according to the (US) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE version 5.0). By treatment arm and overall.
Occurrence of dose interruption, dose reduction, and discontinuation of study treatment due to adverse events (AEs)
Time Frame: up to 100 days after the last dose of treatment
By treatment arm and overall.
Objective Response Rate (ORR)
Time Frame: Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment
Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\] based on the investigator's assessment) is observed as best overall response. By treatment arm.
Best percentage change from baseline in the tumor size
Time Frame: Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment
Based on the investigator's tumor assessment according to RECIST 1.1. Defined as the change from baseline in percent to the minimal tumor size until tumor progression/recurrence or death (whichever occurs first). By treatment arm.
Proportion of participants who have achieved early tumor shrinkage
Time Frame: up to 4 months after first dose of treatment
Defined as ≥10% decrease in the pretreatment sum of diameters at first post-treatment tumor scan in target lesions. By treatment arm.
Secondary Outcomes
- Time to Response (TTR)(Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment)
- PK assessment: Maximum concentration (Cmax) derived from serum concentration of BNT327(from pre-dose to 15 days after study treatment)
- PK assessment: Area Under the Curve During the Dosing Interval (AUCtau) derived from serum concentration of BNT327(from pre-dose to 15 days after study treatment)
- ORR as assessed by the investigator(Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment)
- Duration of Response (DOR)(Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment)
- Overall Survival (OS)(up to 24 months after completion of study treatment of the last participant)
- OS rate(up to 24 months after completion of study treatment of the last participant)
- Incidence of detectable BNT327 antidrug antibodies in serum(from pre-dose to 100 days after last dose of study treatment)
- Disease Control Rate (DCR)(Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment)
- Progression-Free Survival (PFS)(up to 24 months after completion of study treatment of the last participant)
- PFS rate(up to 24 months after completion of study treatment of the last participant)