Clinical Trials /

BNT151 as a Monotherapy and in Combination With Other Anti-cancer Agents in Patients With Solid Tumors

NCT04455620

Description:

This is an open-label, multicenter Phase I/IIa dose escalation, safety, pharmacokinetic (PK) and pharmacodynamic (PD) trial of BNT151 with expansion cohorts in various solid tumor indications. The trial consists of Part 1, Part 2A and Part 2B with adaptive design elements: The monotherapy dose escalation (Part 1) of this clinical trial will enroll patients with various solid tumors that are metastatic (Stage IV) or unresectable for whom there is no available standard therapy likely to confer clinical benefit, or patients who are not candidates for such available therapy. During combination dose escalation (Part 2A), patients of different specific solid tumors (one cohort per indication) will be enrolled and treated with a combination of BNT151 and the respective standard of care (SoC) treatment. Part 2B is the expansion phase where a predefined number of patients in each indication cohort will be treated with the confirmed recommended phase II dose (RP2D) of BNT151 in combination with respective SoC.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: BNT151 as a Monotherapy and in Combination With Other Anti-cancer Agents in Patients With Solid Tumors
  • Official Title: Phase I/IIa, First-in-human, Open-label, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BNT151 as a Monotherapy and in Combination With Other Anti-cancer Agents in Patients With Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BNT151-01
  • SECONDARY ID: 2019-003572-39
  • NCT ID: NCT04455620

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
BNT151Part 1: BNT151

Purpose

This is an open-label, multicenter Phase I/IIa dose escalation, safety, pharmacokinetic (PK) and pharmacodynamic (PD) trial of BNT151 with expansion cohorts in various solid tumor indications. The trial consists of Part 1, Part 2A and Part 2B with adaptive design elements: The monotherapy dose escalation (Part 1) of this clinical trial will enroll patients with various solid tumors that are metastatic (Stage IV) or unresectable for whom there is no available standard therapy likely to confer clinical benefit, or patients who are not candidates for such available therapy. During combination dose escalation (Part 2A), patients of different specific solid tumors (one cohort per indication) will be enrolled and treated with a combination of BNT151 and the respective standard of care (SoC) treatment. Part 2B is the expansion phase where a predefined number of patients in each indication cohort will be treated with the confirmed recommended phase II dose (RP2D) of BNT151 in combination with respective SoC.

Trial Arms

NameTypeDescriptionInterventions
Part 1: BNT151ExperimentalMonotherapy dose escalation in patients with advanced solid malignancies until the maximum tolerated dose (MTD) and/or RP2D
  • BNT151

Eligibility Criteria

        Inclusion Criteria:

          -  Histological documentation of the original primary tumor via a pathology report.

          -  Measurable disease per RECIST1.1.

        For Part 1:

          -  Histologically confirmed solid tumor that is metastatic (Stage IV) or unresectable and
             for whom there is no available standard therapy likely to confer clinical benefit, or
             patient who is not a candidate for such available therapy. If there is no
             contraindication, patients should have exhausted all SoC therapies before entering the
             trial.

        For all Parts:

          -  ≥18 years of age.

          -  Must sign an informed consent form (ICF) indicating that he or she understands the
             purpose and procedures required for the trial and are willing to participate in the
             trial prior to any trial-related assessments or procedures.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          -  Adequate coagulation function at screening as required by the protocol.

          -  Adequate hematologic function at screening as required by the protocol.

          -  Adequate hepatic function at screening as required by the protocol.

          -  Adequate renal function at screening as required by the protocol.

          -  Able and willing to attend trial visits as required by the protocol.

          -  Women of childbearing potential (WOCBP) must have a negative serum (beta-human
             chorionic gonadotropin [beta-hCG]) test/value at screening. Patients who are
             postmenopausal or permanently sterilized can be considered as not having reproductive
             potential.

          -  WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted
             reproduction during the entire trial, until 6 months after last BNT151 treatment.

          -  A man who is sexually active with a woman of childbearing potential and has not had a
             vasectomy must agree to use a barrier method of birth control, e.g. either condom with
             spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
             or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men
             must also not donate sperm during the trial and for 6 months after receiving the last
             dose of BNT151.

        Exclusion Criteria:

          -  Use of any investigational medical product or device within 28 days before
             administration of first dose of trial treatment.

          -  Has been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or
             tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever is longer) of the
             start of trial treatment; immunotherapy/monoclonal antibodies within 3 weeks of the
             start of trial treatment; any live vaccine within 4 weeks of the start of trial
             treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6
             weeks of the start of trial treatment.

          -  Ongoing participation in the active treatment phase of interventional clinical trial.

          -  Receives concurrent systemic (oral or IV) steroid therapy >10 mg prednisone daily or
             its equivalent for an underlying condition.

          -  Has had major surgery within the 4 weeks before the first dose of BNT151.

          -  Ongoing or active infection requiring IV treatment with anti-infective therapy that
             has been administered less than 2 weeks prior to the first dose of BNT151.

          -  Has ongoing side effects to any prior therapy or procedures for any medical condition
             not recovered to National Cancer Institute Common Terminology Criteria for Adverse
             Events (NCI CTCAE) v5.0 Grade ≤1.

        Medical conditions:

          -  Current evidence of new or growing brain or leptomeningeal metastases during
             screening. Patients with known brain metastases may be eligible if they:

          -  had radiotherapy, surgery or stereotactic surgery for the brain metastases;

          -  have no neurological symptoms (excluding Grade ≤2 neuropathy);

          -  have stable brain metastasis on the computed tomography (CT) or magnetic resonance
             imaging (MRI) scan within 4 weeks before signing the informed consent;

          -  are not undergoing acute corticosteroid therapy or steroid taper.

          -  Has a history of a cerebrovascular accident or transient ischemic attack less than 6
             months ago.

          -  Effusions (pleural, pericardial, or ascites) requiring drainage.

          -  History of autoimmune disease active or past including but not limited to inflammatory
             bowel disease, systemic lupus erythematosus (SLE), ankylosing spondylitis,
             scleroderma, or multiple sclerosis. Has any active immunologic disorder requiring
             immunosuppression with steroids or other immunosuppressive agents (e.g., azathioprine,
             cyclosporine A) with the exception of patients with isolated vitiligo, resolved
             childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism,
             and patients with a history of Grave's disease with stable thyroid function. Patients
             with controlled hyperthyroidism must be negative for thyroglobulin, thyroid peroxidase
             antibodies, and thyroid stimulating immunoglobulin prior to administration of trial
             treatment.

          -  Known history of seropositivity for human immunodeficiency virus (HIV) with CD4+
             T˗cell (CD4+) counts <350 cells/uL and with a history of acquired immunodeficiency
             syndrome (AIDS)-defining opportunistic infections.

          -  Known history/positive serology for hepatitis B requiring active antiviral therapy
             (unless immune due to vaccination or resolved natural infection or unless passive
             immunization due to immunoglobulin therapy). Patients with positive serology must have
             HBV viral load below the limit of quantification.

          -  Active HCV infection; patients who have completed curative antiviral treatment with
             HCV viral load below the limit of quantification are allowed.

          -  Known hypersensitivity to a component of any trial treatment.

          -  Any contraindication to the combination therapies as per United States Prescribing
             Information (USPI) or Summary of Product Characteristics (SmPC) for patients receiving
             BNT151 in combination with other systemic anticancer agent(s).

          -  Another primary malignancy that has not been in remission for at least 2 years, with
             the exception of those with a negligible risk of metastasis or death (including but
             not limited to adequately treated carcinoma in situ of the cervix, basal or squamous
             cell skin cancer, localized prostate cancer, or ductal carcinoma in situ).

        Other comorbidities:

          -  Abnormal ECGs that are clinically significant, such as Fridericia-corrected QT
             prolongation >480 ms.

          -  In the opinion of the treating investigator, has any concurrent conditions that could
             pose an undue medical hazard or interfere with the interpretation of the trial
             results; these conditions include, but are not limited to:

          -  Ongoing or active infection requiring antibiotic/antiviral/antifungal therapy

          -  Concurrent congestive heart failure (New York Heart Association [NYHA] Functional
             Classification Class III or IV)

          -  Concurrent unstable angina

          -  Concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial
             fibrillation)

          -  Acute coronary syndrome within the previous 6 months

          -  Pulmonary embolism within the previous 3 months

          -  Significant pulmonary disease (shortness of breath at rest or on mild exertion) for
             example due concurrent severe obstructive pulmonary disease.

          -  Cognitive, psychological or psychosocial impediment that would impair the ability of
             the patient to receive therapy according to the protocol or adversely affect the
             ability of the patient to comply with the informed consent process, protocol, or
             protocol-required visits and procedures.

          -  Is pregnant or breastfeeding.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Occurrence of dose limiting toxicities (DLTs) within a patient during the DLT evaluation period.
Time Frame:up to 21 days
Safety Issue:
Description:The intensity of an TEAE will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v.5.0).

Secondary Outcome Measures

Measure:Overall response rate (ORR) is defined as the proportion of patients in whom a complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors [RECIST 1.1]) is observed as best overall response.
Time Frame:through study completion, an average of 6 months
Safety Issue:
Description:
Measure:Disease control rate (DCR) is defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1, SD assessed at least 6 weeks after first dose) is observed as best overall response.
Time Frame:through study completion, an average of 6 months
Safety Issue:
Description:
Measure:Duration of response (DOR) is defined as the time from first overall response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (Progressive disease (PD) per RECIST 1.1) or death from any cause, whichever occurs first.
Time Frame:through study completion, an average of 6 months
Safety Issue:
Description:
Measure:Time to progression (TPP) is defined as the time from first dose of IMP to objective tumor progression (PD per RECIST 1.1).
Time Frame:through study completion, an average of 6 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BioNTech SE

Last Updated

February 23, 2021