A Phase I/II, Multi-site, Open-label, Two-part Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of BNT323 in Combination With BNT327 in Participants With Advanced Breast Cancer

Plain English Summary

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 is a Phase 2 clinical trial sponsored by BioNTech SE studying Locally Advanced Breast Cancer, Unresectable Breast Carcinoma, Metastatic Breast Cancer. This trial is testing a new combination of two investigational drugs, BNT323 and BNT327, to see if it's safe and effective for advanced breast cancer. It is for patients with advanced, unresectable, or metastatic breast cancer, including various HER2 statuses and triple-negative breast cancer. Participation involves receiving the investigational drugs intravenously and undergoing regular medical assessments and tests. Alternative treatments may include standard chemotherapy, hormone therapy, targeted therapy, or immunotherapy, depending on the specific type and stage of breast cancer. The trial aims to enroll 380 participants.

Official 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-positive, HER2-low (immunohistochemistry \[IHC\] 1+ or IHC 2+/in situ hybridization -), HER2-ultralow (IHC 0, with membrane staining) or HER2-null breast cancer (BC), or triple-negative breast cancer (TNBC).

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with pathologically confirmed breast cancer that is locally advanced, cannot be removed by surgery, or has spread to other parts of the body. Individuals with a confirmed HER2 status (including HER2-positive, HER2-low, HER2-ultralow, HER2-null) or triple-negative breast cancer. Patients must have measurable disease and adequate heart function (left ventricular ejection fraction of at least 55%). Individuals who have had certain prior treatments (like other topoisomerase I inhibitors or specific bispecific antibodies) or have uncontrolled medical conditions may not be eligible. This trial is studying Locally Advanced Breast Cancer, Unresectable Breast Carcinoma, Metastatic Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures will determine if the combination treatment is safe, if the optimal dose can be found, and how well it shrinks tumors or controls the cancer's growth. The specific primary outcome measures are: 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); 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); 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); Part 2 - Objective response rate (ORR) (From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a significant need for new treatment options for patients with advanced breast cancer, particularly those with difficult-to-treat subtypes or who have not responded to existing th Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Locally Advanced Breast Cancer, Unresectable Breast Carcinoma, Metastatic Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial represents an investment in novel combination therapies for a large market of breast cancer patients, with potential for significant impact if successful, though early-phase trials carry in Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of BNT323 and BNT327, and how this combination might fit with your specific cancer type and previous treatments. Participation involves regular visits for drug infusions, blood tests, imaging scans to check tumor response, and monitoring for side effects. Be prepared to report any new or worsening symptoms promptly to the study team. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 380 participants

Interventions

• DRUG: BNT323 — Intravenous infusion
• DRUG: BNT327 — Intravenous infusion

Primary Outcomes

• 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)
• 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)
• 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)
• Part 2 - Objective response rate (ORR) (From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.)

Secondary Outcomes

• Part 1 - ORR (From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.)
• Part 2 - Duration of response (DoR) (From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.)
• Part 2 - Disease control rate (DCR) (From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.)
• Part 2 - Time to response (TTR) (From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.)
• Part 2 Cohort 1 only - Progression free survival (PFS) (From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.)

Full Eligibility Criteria

Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):

* Have pathologically documented BC that:

  * Is locally advanced, unresectable or metastatic.
  * Has a confirmed HER2 status as determined by the local laboratory (Part 1, Part 2 Cohorts 2 and 4) or the central laboratory (Part 2, Cohorts 1 and 3) from the most recently collected pre-randomization tumor sample.
  * Has a documented history of HER2 expression consistent with the subgroup definitions (i.e., HER2-low, HER2-ultralow, HER2-null, HER2-positive, or TNBC) as per current American Society of Clinical Oncology/College of American Pathologists guidelines.
* Have measurable disease defined by RECIST v1.1.
* Has left ventricular ejection fraction ≥55% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.

Key Exclusion Criteria:

* Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
* Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.
* 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.
* 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.
* Had prior treatment with topoisomerase I inhibitors, including ADCs with topoisomerase I inhibitor payloads such as trastuzumab deruxtecan.
* 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. Note: Prior treatment with PD-1/VEGF bispecific antibodies, PD-1/PD-L1 inhibitors or anti-VEGF therapies are permitted.
  * 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.

Trial Locations

• Beverly Hills Cancer Center, Beverly Hills, California, United States
• Hematology - Oncology Associates of the Treasure Coast, Port Saint Lucie, Florida, United States
• Winship Cancer Institute of Emory University, Atlanta, Georgia, United States
• START Midwest, LLC, Grand Rapids, Michigan, United States
• Saint Luke's Hospital of Kansas City, Kansas City, Missouri, United States
• Washington University School of Medicine, St Louis, Missouri, United States
• Summit Medical Group, Florham Park, New Jersey, United States
• Memorial Sloan Kettering Hospital, New York, New York, United States
• South Texas Accelerated Research Therapeutics (START), LLC, San Antonio, Texas, United States
• Sunnybrook Health Sciences Centre, Toronto, Canada
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Metastatic Breast Cancer
• Locally Advanced Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• Hormone Receptor-Negative Breast Cancer
• HER2-Positive Breast Cancer
• HER2-Low Breast Cancer
• Triple-Negative Breast Cancer
• Oncology
• Cancer Therapeutics

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