A Clinical Study to Find the Optimal Dose of an Investigational Treatment Called BNT323 When Used in Combination With Another Investigational Treatment, BNT327, and to Test if That Combination Treatment is Safe and Beneficial for Patients With Advanced Breast Cancer
- Conditions
- Advanced Breast CancerMetastatic Breast Cancer
- Interventions
- Registration Number
- NCT06827236
- Lead Sponsor
- BioNTech SE
- Brief Summary
This is a Phase I/II, multi-site, open-label, two-part study designed to evaluate the efficacy, safety, optimized dose and contribution of components of BNT323 in combination with BNT327 in participants with hormone receptor-positive (HR+) or hormone receptor-negative (HR-), Human epidermal growth factor receptor (HER)2-low (immunohistochemistry \[IHC\] 1+ or IHC 2+/in situ hybridization -), HER2-ultralow (IHC 0, with membrane staining), or HER2-null breast cancer (BC).
- Detailed Description
The study consists of two parts:
* Part 1 - Dose escalation: In Part 1 of the study, participants with histologically confirmed, chemotherapy-pretreated advanced HR+, HER2-low or HER2-ultralow BC will receive BNT323 in combination with BNT327 (BNT323 + BNT327) in a dose escalation design. This will define the recommended Phase 2 dose (RP2D) for the BNT323 + BNT327 combination therapy.
* Part 2 - Dose optimization and exploratory cohorts: Part 2 will be an expansion phase, aiming to evaluate the efficacy and safety of the optimal dose combination and providing a more robust comparison against the other treatments. It will start once the enrollment in Part 1 is completed and the sponsor in conjunction with the Safety Review Committee has assessed available Part 1 efficacy and safety data. Part 2 of the study will have three cohorts, i.e., Cohorts 1 (dose optimization cohort), and Cohorts 2 and 3 (exploratory cohorts).
Randomization is planned for Cohort 1 in Part 2, i.e., participants will be randomized in 2:2:1:1 ratio into one of the four arms (RP2D of BNT323 + BNT327, lower dose of RP2D of BNT323 + BNT327, BNT323 monotherapy, and BNT327 monotherapy). No randomization is planned for any other cohort in Part 2.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 320
Not provided
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Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
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Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.
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Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
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Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
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Had prior treatment with topoisomerase I inhibitors, including ADCs with exatecans.
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Have received any of the following therapies or drugs prior to the initiation of the study:
- Participants who have previously been randomized to or received treatment in a previous study with BNT323, regardless of treatment assignment.
- Participants who received prior treatment with a PD-L1/VEGF bispecific antibody.
- Have received other systemic immunostimulatory agents or immunosuppressive therapies (such as interferon-α, interleukin-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.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part1 - BNT323 + BNT327 combination therapy BNT327 Escalating dose levels (DLs) of BNT323 and BNT327 to define RP2D. Six DLs are planned, i.e., DL0-1, DL1-1, DL2-1, DL0-0, DL1-0, DL2-0, a combination of three different DLs for BNT323 (DL0, DL1, and DL2) and two DLs for BNT327 (DL0 and DL1). Part 2 Cohort 1 - RP2D of BNT323 + BNT327 BNT323 - Part 2 Cohort 1 - RP2D of BNT323 + BNT327 BNT327 - Part 2 Cohort 1 - Lower dose or RP2D of BNT323 + BNT327 BNT323 - Part 2 Cohort 1 - Lower dose or RP2D of BNT323 + BNT327 BNT327 - Part 2 Cohort 1 - BNT327 monotherapy BNT327 BNT327 monotherapy at a fixed dose Part 2 Cohort 2 - Selected dose level of BNT323 + BNT327 BNT327 - Part 2 Cohort 1 - BNT323 monotherapy BNT323 BNT323 monotherapy at a fixed dose Part 2 Cohort 2 - Selected dose level of BNT323 + BNT327 BNT323 - Part 2 Cohort 3 - Selected dose level of BNT323 + BNT327 BNT323 - Part1 - BNT323 + BNT327 combination therapy BNT323 Escalating dose levels (DLs) of BNT323 and BNT327 to define RP2D. Six DLs are planned, i.e., DL0-1, DL1-1, DL2-1, DL0-0, DL1-0, DL2-0, a combination of three different DLs for BNT323 (DL0, DL1, and DL2) and two DLs for BNT327 (DL0 and DL1). Part 2 Cohort 3 - Selected dose level of BNT323 + BNT327 BNT327 -
- Primary Outcome Measures
Name Time Method Part 1 - Occurrence of dose limiting toxicities (DLTs) During the DLT evaluation period (Cycle 1), i.e., the time of initiation of the first dose of investigational medicinal product (IMP) up to 21 days By dose level.
Occurrence of Treatment-emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious adverse events (SAEs), treatment-related TEAEs, treatment-related Grade ≥3 TEAEs, and treatment-related SAEs From the time of initiation of the first dose of IMP to 90 days after the last IMP dose In Part 1 by dose level. In Part 2 by cohort and arm.
Occurrence of dose interruption, reduction, and discontinuation due to TEAEs From the time of initiation of the first dose of IMP to 90 days after the last IMP dose In Part 1 by dose level. In Part 2 by cohort and arm.
Part 2 - Objective response rate (ORR) From the time of initiation of the first dose of IMP to end of study, i.e., up to 54 months ORR 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 cohort and arm.
- Secondary Outcome Measures
Name Time Method Part 1 - ORR From the time of initiation of the first dose of IMP to end of study, i.e., up to 54 months ORR defined as the proportion of participants in whom a confirmed CR or PR (per RECIST 1.1 based on the investigator's assessment) is observed as best overall response.
By dose level.Part 2 - Duration of response (DoR) From the time of initiation of the first dose of IMP to end of study, i.e., up to 54 months DoR defined as the time from first objective response (CR or PR per RECIST 1.1 based on the investigator's assessment) to first occurrence of objective tumor progression (progressive disease \[PD\], per RECIST 1.1 based on the investigator's assessment) or death from any cause, whichever occurs first.
By cohort and arm.Part 2 - Disease control rate (DCR) From the time of initiation of the first dose of IMP to end of study, i.e., up to 54 months DCR defined as the proportion of participants with confirmed CR, PR, or stable disease (per RECIST 1.1 based on the investigator's assessment) as best overall response.
By cohort and arm.Part 2 - Time to response (TTR) From the time of initiation of the first dose of IMP to end of study, i.e., up to 54 months TTR defined as the time from first dose of IMP to first objective response (CR or PR per RECIST 1.1 based on the investigator's assessment).
By cohort and arm.Part 2 Cohort 1 only - Progression free survival (PFS) From the time of initiation of the first dose of IMP to end of study, i.e., up to 54 months PFS based on the investigator's assessment defined as the time from first dose of IMP to the first objective tumor progression (PD per RECIST 1.1) or death from any cause, whichever occurs first.
By arm.
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Trial Locations
- Locations (2)
Hematology - Oncology Associates of the Treasure Coast
🇺🇸Port Saint Lucie, Florida, United States
Institute of Oncology Arensia Exploratory Medicine
🇲🇩Chisinau, Moldova, Republic of