<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04455620</url>
  </required_header>
  <id_info>
    <org_study_id>BNT151-01</org_study_id>
    <secondary_id>2019-003572-39</secondary_id>
    <nct_id>NCT04455620</nct_id>
  </id_info>
  <brief_title>BNT151 as a Monotherapy and in Combination With Other Anti-cancer Agents in Patients With Solid Tumors</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BioNTech SE</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BioNTech SE</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, multicenter Phase I/IIa dose escalation, safety, pharmacokinetic (PK)&#xD;
      and pharmacodynamic (PD) trial of BNT151 with expansion cohorts in various solid tumor&#xD;
      indications. The trial consists of Part 1, Part 2A and Part 2B with adaptive design elements:&#xD;
&#xD;
      The monotherapy dose escalation, (Part 1) of this clinical trial will enroll patients with&#xD;
      various solid tumors that are metastatic or of advanced unresectable stage for whom there is&#xD;
      no available standard therapy likely to confer clinical benefit, or patients who are not&#xD;
      candidates for such available therapy. The Part 1 of the trial also plans to implement a&#xD;
      dedicated biomarker cohort in BNT151 monotherapy: The Biomarker Cohort will recruit patients&#xD;
      at selected sites in the US only. The objective of the cohort is to observe PD activity and&#xD;
      drug-induced changes in the blood and tumor.&#xD;
&#xD;
      During combination dose escalation (Part 2A), patients of different specific solid tumors&#xD;
      (one cohort per indication) will be enrolled and treated with a combination of BNT151 and the&#xD;
      respective standard of care (SoC) treatment.&#xD;
&#xD;
      Part 2B is the expansion phase where a predefined number of patients in each indication&#xD;
      cohort will be treated with the confirmed recommended phase II dose (RP2D) of BNT151 in&#xD;
      combination with respective SoC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 26, 2021</start_date>
  <completion_date type="Anticipated">June 2026</completion_date>
  <primary_completion_date type="Anticipated">February 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of dose limiting toxicities (DLTs) within a patient during the DLT evaluation period in Part 1.</measure>
    <time_frame>up to 21 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of treatment emergent adverse event (TEAE) within a patient including Grade ≥3, serious, fatal TEAE by relationship.</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <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).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of dose reduction and discontinuation of investigational medicinal product (IMP) within a patient due to TEAE.</measure>
    <time_frame>through treatment completion, an average of 4 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective 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.</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <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.</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) is defined as the time from first objective 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.</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">84</enrollment>
  <condition>Solid Tumor</condition>
  <arm_group>
    <arm_group_label>Part 1: BNT151</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Monotherapy dose escalation in patients with advanced solid malignancies until the maximum tolerated dose (MTD) and/or RP2D</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BNT151</intervention_name>
    <description>intravenous</description>
    <arm_group_label>Part 1: BNT151</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological documentation of the original primary tumor via a pathology report.&#xD;
&#xD;
          -  Measurable disease per RECIST1.1.&#xD;
&#xD;
        For Part 1:&#xD;
&#xD;
          -  Histologically confirmed solid tumor that is metastatic or of advanced unresectable&#xD;
             stage and for whom there is no available standard therapy likely to confer clinical&#xD;
             benefit, or patient who is not a candidate for such available therapy. If there is no&#xD;
             contraindication, patients should have exhausted all SoC therapies before entering the&#xD;
             trial, if possible.&#xD;
&#xD;
        For all Parts:&#xD;
&#xD;
          -  ≥18 years of age.&#xD;
&#xD;
          -  Must sign an informed consent form (ICF) indicating that he or she understands the&#xD;
             purpose and procedures required for the trial and are willing to participate in the&#xD;
             trial prior to any trial-related assessments or procedures.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.&#xD;
&#xD;
          -  Adequate coagulation function at screening as required by the protocol.&#xD;
&#xD;
          -  Adequate hematologic function at screening as required by the protocol.&#xD;
&#xD;
          -  Adequate hepatic function at screening as required by the protocol.&#xD;
&#xD;
          -  Adequate renal function at screening as required by the protocol.&#xD;
&#xD;
          -  Able and willing to attend trial visits as required by the protocol.&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP) must have a negative serum (beta-human&#xD;
             chorionic gonadotropin [beta-hCG]) test/value at screening. Patients who are&#xD;
             postmenopausal or permanently sterilized can be considered as not having reproductive&#xD;
             potential.&#xD;
&#xD;
          -  WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted&#xD;
             reproduction during the entire trial, until 6 months after last BNT151 treatment.&#xD;
&#xD;
          -  A man who is sexually active with a woman of childbearing potential and has not had a&#xD;
             vasectomy must agree to use a barrier method of birth control, e.g. either condom with&#xD;
             spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm&#xD;
             or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men&#xD;
             must also not donate sperm during the trial and for 6 months after receiving the last&#xD;
             dose of BNT151.&#xD;
&#xD;
          -  WOCBP must agree to use highly effective contraception during the trial and for 6&#xD;
             months after receiving the last dose of BNT151. Birth control methods are considered&#xD;
             highly effective if they have a failure rate of less than 1% per year, when used&#xD;
             consistently and correctly.&#xD;
&#xD;
          -  Biomarker Cohort: At selected US sites only: at enrollment patients must agree to have&#xD;
             one pre-dose biopsy and lesion that is deemed accessible by the investigator. If&#xD;
             possible, at least one on-treatment biopsy should be accessible from same tumor&#xD;
             lesion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of any investigational medical product or device within 28 days before&#xD;
             administration of first dose of trial treatment.&#xD;
&#xD;
          -  Has been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or&#xD;
             tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever is longer) of the&#xD;
             start of trial treatment; immunotherapy/monoclonal antibodies within 3 weeks of the&#xD;
             start of trial treatment; any live vaccine within 4 weeks of the start of trial&#xD;
             treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6&#xD;
             weeks of the start of trial treatment.&#xD;
&#xD;
          -  Ongoing participation in the active treatment phase of interventional clinical trial.&#xD;
&#xD;
          -  Receives concurrent systemic (oral or IV) steroid therapy &gt;10 mg prednisone daily or&#xD;
             its equivalent for an underlying condition.&#xD;
&#xD;
          -  Has had major surgery within the 4 weeks before the first dose of BNT151.&#xD;
&#xD;
          -  Ongoing or active infection requiring IV treatment with anti-infective therapy that&#xD;
             has been administered less than 2 weeks prior to the first dose of BNT151.&#xD;
&#xD;
          -  Has ongoing side effects to any prior therapy or procedures for any medical condition&#xD;
             not recovered to National Cancer Institute Common Terminology Criteria for Adverse&#xD;
             Events (NCI CTCAE) v5.0 Grade ≤1.&#xD;
&#xD;
        Medical conditions:&#xD;
&#xD;
          -  Current evidence of new or growing brain or leptomeningeal metastases during&#xD;
             screening. Patients with known brain metastases may be eligible if they:&#xD;
&#xD;
          -  had radiotherapy, surgery or stereotactic surgery for the brain metastases;&#xD;
&#xD;
          -  have no neurological symptoms (excluding Grade ≤2 neuropathy);&#xD;
&#xD;
          -  have stable brain metastasis on the computed tomography (CT) or magnetic resonance&#xD;
             imaging (MRI) scan within 4 weeks before signing the informed consent;&#xD;
&#xD;
          -  are not undergoing acute corticosteroid therapy or steroid taper.&#xD;
&#xD;
          -  Has a history of a cerebrovascular accident or transient ischemic attack less than 6&#xD;
             months ago.&#xD;
&#xD;
          -  Effusions (pleural, pericardial, or ascites) requiring drainage.&#xD;
&#xD;
          -  History of autoimmune disease active or past including but not limited to inflammatory&#xD;
             bowel disease, systemic lupus erythematosus (SLE), ankylosing spondylitis,&#xD;
             scleroderma, or multiple sclerosis. Has any active immunologic disorder requiring&#xD;
             immunosuppression with steroids or other immunosuppressive agents (e.g., azathioprine,&#xD;
             cyclosporine A) with the exception of patients with isolated vitiligo, resolved&#xD;
             childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism,&#xD;
             and patients with a history of Grave's disease with stable thyroid function. Patients&#xD;
             with controlled hyperthyroidism must be negative for thyroglobulin, thyroid peroxidase&#xD;
             antibodies, and thyroid stimulating immunoglobulin prior to administration of trial&#xD;
             treatment.&#xD;
&#xD;
          -  Known history of seropositivity for human immunodeficiency virus (HIV) with CD4+&#xD;
             T˗cell (CD4+) counts &lt;350 cells/µL and with a history of acquired immunodeficiency&#xD;
             syndrome (AIDS)-defining opportunistic infections.&#xD;
&#xD;
          -  Known history/positive serology for hepatitis B requiring active antiviral therapy&#xD;
             (unless immune due to vaccination or resolved natural infection or unless passive&#xD;
             immunization due to immunoglobulin therapy). Patients with positive serology must have&#xD;
             HBV viral load below the limit of quantification.&#xD;
&#xD;
          -  Active HCV infection; patients who have completed curative antiviral treatment with&#xD;
             HCV viral load below the limit of quantification are allowed.&#xD;
&#xD;
          -  Known hypersensitivity to a component of any trial treatment.&#xD;
&#xD;
          -  Any contraindication to the combination therapies as per United States Prescribing&#xD;
             Information (USPI) or Summary of Product Characteristics (SmPC) for patients receiving&#xD;
             BNT151 in combination with other systemic anticancer agent(s).&#xD;
&#xD;
          -  Another primary malignancy that has not been in remission for at least 2 years, with&#xD;
             the exception of those with a negligible risk of metastasis or death (including but&#xD;
             not limited to adequately treated carcinoma in situ of the cervix, basal or squamous&#xD;
             cell skin cancer, localized prostate cancer, or ductal carcinoma in situ).&#xD;
&#xD;
        Other comorbidities:&#xD;
&#xD;
          -  Abnormal ECGs that are clinically significant, such as Fridericia-corrected QT&#xD;
             prolongation &gt;480 ms.&#xD;
&#xD;
          -  In the opinion of the treating investigator, has any concurrent conditions that could&#xD;
             pose an undue medical hazard or interfere with the interpretation of the trial&#xD;
             results; these conditions include, but are not limited to:&#xD;
&#xD;
          -  Ongoing or active infection requiring antibiotic/antiviral/antifungal therapy&#xD;
&#xD;
          -  Concurrent congestive heart failure (New York Heart Association [NYHA] Functional&#xD;
             Classification Class III or IV)&#xD;
&#xD;
          -  Concurrent unstable angina&#xD;
&#xD;
          -  Concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial&#xD;
             fibrillation)&#xD;
&#xD;
          -  Acute coronary syndrome within the previous 6 months&#xD;
&#xD;
          -  Pulmonary embolism within the previous 3 months&#xD;
&#xD;
          -  Significant pulmonary disease (shortness of breath at rest or on mild exertion) for&#xD;
             example due concurrent severe obstructive pulmonary disease.&#xD;
&#xD;
          -  Cognitive, psychological or psychosocial impediment that would impair the ability of&#xD;
             the patient to receive therapy according to the protocol or adversely affect the&#xD;
             ability of the patient to comply with the informed consent process, protocol, or&#xD;
             protocol-required visits and procedures.&#xD;
&#xD;
          -  Is pregnant or breastfeeding.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>BioNTech Responsible Person</last_name>
    <role>Study Director</role>
    <affiliation>BioNTech SE</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>BioNTech clinical trials patient information</last_name>
    <phone>+49 6131 9084</phone>
    <phone_ext>0</phone_ext>
    <email>patients@biontech.de</email>
  </overall_contact>
  <location>
    <facility>
      <name>Yale Cancer Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute at Tennessee Oncology</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>NEXT Oncology</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Vall d´Hebron Institute of Oncology (VHIO)</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>START Madrid - HM CIOCC</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>United Kingdom</country>
  </removed_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>September 4, 2023</last_update_submitted>
  <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Solid Tumors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04455620
org study id: BNT151-01
secondary id: 2019-003572-39
nct id: NCT04455620
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
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 or of advanced unresectable stage for whom there is
      no available standard therapy likely to confer clinical benefit, or patients who are not
      candidates for such available therapy. The Part 1 of the trial also plans to implement a
      dedicated biomarker cohort in BNT151 monotherapy: The Biomarker Cohort will recruit patients
      at selected sites in the US only. The objective of the cohort is to observe PD activity and
      drug-induced changes in the blood and tumor.

      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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of dose limiting toxicities (DLTs) within a patient during the DLT evaluation period in Part 1.
time frame: up to 21 days
measure: Occurrence of treatment emergent adverse event (TEAE) within a patient including Grade ≥3, serious, fatal TEAE by relationship.
time frame: through study completion, an average of 6 months
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).
measure: Occurrence of dose reduction and discontinuation of investigational medicinal product (IMP) within a patient due to TEAE.
time frame: through treatment completion, an average of 4 months
measure: Objective 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
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
measure: Duration of response (DOR) is defined as the time from first objective 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
arm group label: Part 1: BNT151
arm group type: Experimental
description: Monotherapy dose escalation in patients with advanced solid malignancies until the maximum tolerated dose (MTD) and/or RP2D
intervention type: Biological
intervention name: BNT151
description: intravenous
arm group label: Part 1: BNT151
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: BioNTech Responsible Person
role: Study Director
affiliation: BioNTech SE
last name: BioNTech clinical trials patient information
phone: +49 6131 9084
phone ext: 0
email: patients@biontech.de
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: Spain
country: United States
country: United Kingdom
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No