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Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Breast Cancer, When Given in Combination With Chemotherapy

PHASE2ACTIVE_NOT_RECRUITING

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).

Study details:

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).

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Have given informed consent by signing and dating an informed consent form before initiation of any study-specific procedures.
  2. Male or female, aged ≥18 years at the time of giving informed consent.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. They have had a recurrence-free interval of ≥6 months if they have received treatment with curative intent in the past.
  9. Have provided a tissue sample, archival or fresh, during the screening period (bone biopsies, fine needle aspiration biopsies, and samples from pleural or peritoneal fluid are not acceptable; participants with only one target lesion are not eligible to provide a biopsy). If an archival tumor sample is not available, the participant must undergo a fresh biopsy, if medically feasible to be eligible for the study.
  10. Have at least one measurable lesion as the targeted lesion based on RECIST version 1.1.
  11. Eastern Cooperative Oncology Group performance status of 0 or 1.
  12. Have a minimum life expectancy of >3 months.
  13. Have adequate organ function, as defined below:
  14. Are women of childbearing potential (WOCBP) who have a negative serum beta human chorionic gonadotropin pregnancy test.
  15. Are WOCBP who agree to practice a highly effective form of contraception and to require the use of barrier contraception methods, starting at the time of giving informed consent and continuously until 6 months after receiving the last study treatment.
  16. Are men who are sterile or if they are potentially fertile (i.e., are not surgically [e.g., have had a vasectomy] or congenitally sterile) and sexually active with a partner of childbearing potential, who agree to use condoms and to ask their sexual partners to practice a highly effective form of contraception during the study, starting at the time of giving informed consent and continuously until 6 months after receiving the last dose of IMP.
  17. Agree not to donate germ (ova, oocytes, sperm) for the purposes of assisted reproduction during study, starting at the time of giving informed consent and continuously until 6 months after receiving the last dose of IMP.

Exclusion criteria

  1. 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.
  2. 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.
  3. Have received any of the following therapies or drugs prior to the initiation of study:
  4. Participants who received prior treatment with a PD(L)-1/Vascular Endothelial Growth Factor bispecific antibody.
  5. 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.
  6. 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).
  7. 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.
  8. Have been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of study treatment.
  9. Received broad-spectrum IV antibiotics therapy within 3 weeks prior to initiation of study treatment.
  10. 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.
  11. Have undergone major organ surgery (core needle biopsies are allowed >7 days prior study start), significant trauma, or invasive dental procedures (such as dental implants) within 28 days prior to the initiation of study treatment or plan to undergo elective surgery during the study. Placement of vascular infusion devices is allowed.
  12. Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
  13. Have spinal cord compression or central nervous system metastases that is untreated and symptomatic or requires treatment with corticosteroids or anticonvulsants for associated-symptom control.
  14. Have active autoimmune disease that has required systemic treatment in the past 2 years.
  15. Have had other malignant tumors within 2 years prior to the study treatment are not allowed.
  16. Have any of the following heart conditions within 6 months prior to the study treatment:
  17. Have any of the following hypertension or diabetic conditions prior to initiation of study treatment:
  18. Have serious non-healing wounds, ulcers, or bone fractures.
  19. Participants with evidence of major coagulation disorders or other significant risks of hemorrhage.
  20. Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
  21. Have uncontrolled tumor-related pain requiring analgesic treatment not managed by a stable analgesic regimen.
  22. Have a known or suspected hypersensitivity to the study treatments including any active ingredient or excipients thereof.
  23. Have a known human immunodeficiency virus infection or known acquired immunodeficiency syndrome.
  24. Have a known history/positive serology for hepatitis B requiring active antiviral therapy.
  25. Have active hepatitis C virus infection.
  26. Are subject to exclusion periods from another investigational study.
  27. Are vulnerable individuals, i.e., are individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
  28. Participants with AEs from prior antitumor therapy that have not returned to Grade 1 or below.
  29. Have superior vena cava syndrome or symptoms of spinal cord compression.
  30. Those with active, or a history of, pneumonitis requiring treatment with steroids, or has active, or a history of, interstitial lung disease.
  31. Have active tuberculosis or history of tuberculosis that was not successfully treated.
  32. Have underlying condition(s) that may increase risk of the combination treatment or complicate the interpretation of toxicities and AEs, as judged by the investigator.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE2

trial

Study ID

NCT06449222

Intervention or treatment

DRUG: BNT327 Dose Level 1 (DL1)

DRUG: BNT327 Dose Level 1 (DL2)

DRUG: Nab-placlitaxel

DRUG: Carboplatin

DRUG: Gemcitabine

DRUG: Paclitaxel

DRUG: Eribulin

DRUG: BNT327 Optimized Dose

DRUG: BNT327 Equivalent Q3W Dose

Conditions

  • Locally Advanced Breast Cancer
  • Triple Negative Breast Cancer
  • Metastatic Triple Negative Breast Cancers

  • Condition: Locally Advanced Breast Cancer, Triple Negative Breast Cancer and more

  • DRUG: BNT327 Dose Level 1 (DL1) and other drugs

  • Auchenflower, Australia and more

  • Sponsor: BioNTech SE

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Icon Cancer Care, Wesley Clinic

Select from list below to view details:

  • Icon Cancer Care, Wesley Clinic

    Auchenflower, Australia

  • Peninsula Oncology Centre

    Frankston, Australia

  • Peter MacCallum Cancer Centre

    Melbourne, Australia

  • Mater Hospital Sydney

    Sydney, Australia

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Who is running the clinical trial?

BS

BioNTech SE

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Cohort 1 Arm 1 - BNT327 DL1 + Nab-paclitaxel
  • Not Specified
Drug: BNT327 Dose Level 1 (DL1), Drug: Nab-placlitaxel
    EXPERIMENTAL: Cohort 1 Arm 2 - BNT327 DL2 + Nab-paclitaxel
    • Not Specified
    Drug: BNT327 Dose Level 1 (DL2), Drug: Nab-placlitaxel
      EXPERIMENTAL: Cohort 2 Arm 1 - BNT327 Optimized dose + Paclitaxel
      • Not Specified
      Drug: Paclitaxel, Drug: BNT327 Optimized Dose
        EXPERIMENTAL: Cohort 2 Arm 2 - BNT327 Equivalent Q3W dose + Gemcitabine + Carboplatin
        • Not Specified
        Drug: Carboplatin, Drug: Gemcitabine, Drug: BNT327 Equivalent Q3W Dose
          EXPERIMENTAL: Cohort 2 Arm 3 - BNT327 Equivalent Q3W dose + Eribulin
          • Not Specified
          Drug: Eribulin, Drug: BNT327 Equivalent Q3W Dose

            What is the study measuring?

            Primary Outcome

            MeasureDescriptionTime Frame
            Occurrence of treatment emergent adverse events (TEAEs), adverse events of special interest (AESIs), treatment emergent serious adverse events (SAEs)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.up to 100 days after the last dose of treatment
            Occurrence of dose interruption, dose reduction, and discontinuation of study treatment due to adverse events (AEs)By treatment arm and overall.up to 100 days after the last dose of treatment
            Objective Response Rate (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 treatment arm.Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment
            Best percentage change from baseline in the tumor sizeBased 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.Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment
            Proportion of participants who have achieved early tumor shrinkageDefined as ≥10% decrease in the pretreatment sum of diameters at first post-treatment tumor scan in target lesions. By treatment arm.up to 4 months after first dose of treatment

            Secondary Outcome

            MeasureDescriptionTime Frame
            PK assessment: Maximum concentration (Cmax) derived from serum concentration of BNT327By treatment arm for Cohort 1, Arm 1 and 2, and Cohort 2, Arm 1from pre-dose to 15 days after study treatment
            PK assessment: Area Under the Curve During the Dosing Interval (AUCtau) derived from serum concentration of BNT327If data permits. By treatment arm for Cohort 1, Arm 1 and 2, and Cohort 2, Arm 1from pre-dose to 15 days after study treatment
            Incidence of detectable BNT327 antidrug antibodies in serumNot Specifiedfrom pre-dose to 100 days after last dose of study treatment
            ORR as assessed by the investigatorAs assessed by the investigator (Cohort 2)Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment
            Duration of Response (DOR)Defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression or death from any cause, whichever occurs first based on investigator's reviewUntil end-of-treatment visit, i.e., up to 24 months after the first dose of treatment
            Disease Control Rate (DCR)Defined as the proportion of participants in whom a confirmed CR or PR or stable disease (per RECIST 1.1, stable disease assessed at least 6 weeks after first dose) is observed as best overall response based on the investigator's review.Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment
            Time to Response (TTR)Defined as the time from randomization/assignment to first objective response (CR or PR per RECIST 1.1) based on the investigator's review.Until end-of-treatment visit, i.e., up to 24 months after the first dose of treatment
            Progression-Free Survival (PFS)Based on investigator's review tumor assessment according to RECIST 1.1 is defined as the time from randomization/assignment to first confirmed objective tumor progression (progressive disease per RECIST 1.1), or death from any cause, whichever occurs first.up to 24 months after completion of study treatment of the last participant
            PFS rateAs measured at 6, 12, 18, and 24 monthsup to 24 months after completion of study treatment of the last participant
            Overall Survival (OS)Defined as the time from randomization/assignment to death from any causeup to 24 months after completion of study treatment of the last participant
            OS rateAs measured at 6, 12, 18, and 24 monthsup to 24 months after completion of study treatment of the last participant
            Are you running this trial?If you're a clinic or sponsor, you can claim this study.
            Claim this trial

            References

            Clinical Trials Gov: Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Breast Cancer, When Given in Combination With Chemotherapy

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