Safety, Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Small-cell Lung Cancer in Combination With Chemotherapy
NCT ID: NCT06449209
Last Updated: 2025-11-13
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
ACTIVE_NOT_RECRUITING
Clinical Phase
PHASE2
Total Enrollment
110 participants
Study Classification
INTERVENTIONAL
Study Start Date
2024-08-05
Study Completion Date
2028-05-31
Brief Summary
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This is a Phase II, multi-site, open-label, parallel group study in participants with untreated extended-stage small-cell lung cancer (ES-SCLC) (Cohort 1) or small-cell lung cancer (SCLC) which has progressed on first- or second-line treatment (Cohort 2 and Cohort 3). This study will assess the safety, efficacy, and pharmacokinetics (PK) of BNT327.
Detailed Description
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In Cohort 1 of this study, two dose levels of BNT327 will be studied in combination with etoposide and carboplatin to identify an optimized dose for future clinical investigation.
Cohort 2 and Cohort 3 will explore the combination of two dose levels of BNT327 with paclitaxel, or topotecan in the second- or third-line setting.
Patients will be treated until disease progression, intolerable toxicity, patient withdrawal, study termination or up to 2 years (whichever occurs first).
Participants will be assigned to either Cohort 1 or Cohort 2/Cohort 3 based on their disease type (i.e., untreated ES-SCLC for Cohort 1 and SCLC which has progressed on first- or second-line treatment for Cohort 2 and Cohort 3). Assignment to either Cohort 2 or Cohort 3 will be the investigator's choice.
Participants will be randomized to each arm within each cohort:
* Participants enrolled to Cohort 1 and Cohort 3 will be randomized in a 1:1 ratio to Arm 1 or Arm 2.
* Participants enrolled to Cohort 2 will be randomized in a 2:1 ratio to Arm 1 or Arm 2.
Cohort 2 and Cohort 3 will explore the combination of two dose levels of BNT327 with paclitaxel, or topotecan in the second- or third-line setting.
Patients will be treated until disease progression, intolerable toxicity, patient withdrawal, study termination or up to 2 years (whichever occurs first).
Participants will be assigned to either Cohort 1 or Cohort 2/Cohort 3 based on their disease type (i.e., untreated ES-SCLC for Cohort 1 and SCLC which has progressed on first- or second-line treatment for Cohort 2 and Cohort 3). Assignment to either Cohort 2 or Cohort 3 will be the investigator's choice.
Participants will be randomized to each arm within each cohort:
* Participants enrolled to Cohort 1 and Cohort 3 will be randomized in a 1:1 ratio to Arm 1 or Arm 2.
* Participants enrolled to Cohort 2 will be randomized in a 2:1 ratio to Arm 1 or Arm 2.
Conditions
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Extensive-stage Small-cell Lung Cancer
Small-cell Lung Cancer
Keywords
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Programmed Death-1 (PD-1)
Programmed Death Ligand-1 (PD-L1)
Programmed Death-1 monoclonal antibodies
Combination chemotherapy
Anti vascular endothelial growth factor (VEGF)
Previously treated small-cell lung cancer
Untreated extensive-stage small-cell lung cancer
Dose optimization
Time to progression
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Cohort 1 Arm 1 - BNT327 DL1 + carboplatin + etoposide
Participants with ES-SCLC without prior systemic anticancer therapy received in the ES setting
Group Type
EXPERIMENTAL
BNT327 Dose Level 1 (DL1)
Intervention Type
DRUG
Intravenous (IV) infusion
Etoposide
Intervention Type
DRUG
IV infusion
Carboplatin
Intervention Type
DRUG
IV infusion
Cohort 1 Arm 2 - BNT327 DL2 + carboplatin + etoposide
Participants with ES-SCLC without prior systemic anticancer therapy received in the ES setting
Group Type
EXPERIMENTAL
BNT327 Dose Level 2 (DL2)
Intervention Type
DRUG
IV infusion
Etoposide
Intervention Type
DRUG
IV infusion
Carboplatin
Intervention Type
DRUG
IV infusion
Cohort 2 Arm 1 - BNT327 DL1 + paclitaxel
Participants with SCLC who have disease progression/relapse
Group Type
EXPERIMENTAL
BNT327 Dose Level 1 (DL1)
Intervention Type
DRUG
Intravenous (IV) infusion
Paclitaxel
Intervention Type
DRUG
IV infusion
Cohort 2 Arm 2 - BNT327 DL2 + paclitaxel
Participants with SCLC who have disease progression/relapse
Group Type
EXPERIMENTAL
BNT327 Dose Level 2 (DL2)
Intervention Type
DRUG
IV infusion
Paclitaxel
Intervention Type
DRUG
IV infusion
Cohort 3 Arm 1 - BNT327 DL1 + topotecan
Participants with SCLC who have disease progression/relapse
Group Type
EXPERIMENTAL
BNT327 Dose Level 1 (DL1)
Intervention Type
DRUG
Intravenous (IV) infusion
Topotecan
Intervention Type
DRUG
IV infusion or oral capsules
Cohort 3 Arm 2 - BNT327 DL2 + topotecan
Participants with SCLC who have disease progression/relapse
Group Type
EXPERIMENTAL
BNT327 Dose Level 2 (DL2)
Intervention Type
DRUG
IV infusion
Topotecan
Intervention Type
DRUG
IV infusion or oral capsules
Interventions
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BNT327 Dose Level 1 (DL1)
Intravenous (IV) infusion
Intervention Type
DRUG
BNT327 Dose Level 2 (DL2)
IV infusion
Intervention Type
DRUG
Etoposide
IV infusion
Intervention Type
DRUG
Carboplatin
IV infusion
Intervention Type
DRUG
Paclitaxel
IV infusion
Intervention Type
DRUG
Topotecan
IV infusion or oral capsules
Intervention Type
DRUG
Eligibility Criteria
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Inclusion Criteria
* Cohort 1 only: Have histologically or cytologically confirmed ES-SCLC (using the American Joint Committee on Cancer \[AJCC\]) tumor node metastasis \[TNM\] staging system combined with Veterans Administration Lung Study Group two-stage classification scheme). For AJCC TNM staging system: AJCC 8th edition stage IV (T any, N any, M1a/b/c), or T3\~4 for multiple lung nodules or tumor/nodule volume that cannot be encompassed in a tolerable radiotherapy plan.
* Cohort 1 only: Participants who have not received systemic therapy for ES-SCLC for various reasons including potential intolerance of the standard-of-care per the patient's treating physician's judgment. However, participants with prior chemoradiotherapy for Limited-Stage Small-Cell Lung Cancer (LS-SCLC) must have been treated with curative intent and had a treatment-free interval of at least 6 months since the last systemic anticancer treatment including chemotherapy, radiotherapy, or chemoradiotherapy before the diagnosis of ES-SCLC to be eligible.
* Cohort 2 and Cohort 3 only: Participants with SCLC who have disease progression/relapse after first-line platinum-based chemotherapy with or without immunotherapy, or after first-line platinum-based chemotherapy and one second-line of chemotherapy (not the same chemotherapy agent in the specific arm to be enrolled to) with time to progression ≥3 months during second-line treatment.
* Have given informed consent by signing and dating an informed consent form before initiation of any study-specific procedures.
* Male or female, aged ≥18 years at the time of giving informed consent.
* Are willing and able to comply with scheduled visits, treatment schedule, the planned study assessments, laboratory tests, lifestyle restrictions, and other requirements of the study. This includes that they are able to understand and follow study-related instructions.
* Have at least one measurable lesion as the targeted lesion based on RECIST 1.1. Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures, etc.) are generally not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system metastasis should not be considered as a measurable lesion).
* Eastern Cooperative Oncology Group performance status of 0 or 1.
* Have a minimum life expectancy of \>3 months.
* Have adequate organ function, as defined below:
* Hematology:
* Absolute neutrophil count ≥1.5 × 10\^9/L.
* Platelet count ≥100 × 10\^9/L.
* Hemoglobin ≥90 g/L or 5.6 mmol/L.
* Liver function:
* Total bilirubin ≤1.5 × upper limit of normal (ULN).
* With Gilbert's syndrome total bilirubin \<3 mg/dL and direct bilirubin ≤ULN. Note, Gilbert's syndrome must be documented appropriately as past medical history.
* Participants without liver metastasis alanine aminotransferase and aspartate aminotransferase ≤2 × ULN.
* Participants with liver metastasis alanine aminotransferase and aspartate aminotransferase ≤5 × ULN.
* Albumin ≥3.0 g/dL.
* Renal function: Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min. Cockcroft-Gault formula.
* Qualitative urine protein ≤1+. If qualitative urine protein ≥2+, a 24-hour urine protein quantitative test is required. If the 24-hour urine protein result is \<1 g, the participant can be enrolled.
* Coagulation function: International normalized ratio or prothrombin time and activated partial thromboplastin time ≤1.5 × ULN unless the participant is receiving anticoagulation therapy as long as prothrombin or activated partial thromboplastin is within therapeutic range of intended use of anticoagulant.
* Are women of childbearing potential (WOCBP) who have a negative serum beta-human chorionic gonadotropin test at screening and before each IMP dose. Women born female that are postmenopausal (defined as 12 months with no menses without an alternative medical cause) or permanently sterilized (verified by medical records) will not be considered WOCBP and therefore will not be required to undergo pregnancy testing.
* Are WOCBP who agree to practice a highly effective form of contraception and to require their male sexual partners to use barrier contraception methods (preferably condoms), starting at Screening and continuously until 6 months after receiving the last study treatment.
* Are men who are sexually active with a partner born female and have not had a vasectomy 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 Screening Period and continuously until 6 months after receiving the last dose of IMP.
* Are WOCBP who agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study, starting at the Screening Period and continuously 6 months after receiving the last dose of IMP.
* Are men who are willing to refrain from sperm donation, starting at the Screening Period and continuously until 6 months after the last dose of IMP.
* Cohort 1 only: Participants who have not received systemic therapy for ES-SCLC for various reasons including potential intolerance of the standard-of-care per the patient's treating physician's judgment. However, participants with prior chemoradiotherapy for Limited-Stage Small-Cell Lung Cancer (LS-SCLC) must have been treated with curative intent and had a treatment-free interval of at least 6 months since the last systemic anticancer treatment including chemotherapy, radiotherapy, or chemoradiotherapy before the diagnosis of ES-SCLC to be eligible.
* Cohort 2 and Cohort 3 only: Participants with SCLC who have disease progression/relapse after first-line platinum-based chemotherapy with or without immunotherapy, or after first-line platinum-based chemotherapy and one second-line of chemotherapy (not the same chemotherapy agent in the specific arm to be enrolled to) with time to progression ≥3 months during second-line treatment.
* Have given informed consent by signing and dating an informed consent form before initiation of any study-specific procedures.
* Male or female, aged ≥18 years at the time of giving informed consent.
* Are willing and able to comply with scheduled visits, treatment schedule, the planned study assessments, laboratory tests, lifestyle restrictions, and other requirements of the study. This includes that they are able to understand and follow study-related instructions.
* Have at least one measurable lesion as the targeted lesion based on RECIST 1.1. Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures, etc.) are generally not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system metastasis should not be considered as a measurable lesion).
* Eastern Cooperative Oncology Group performance status of 0 or 1.
* Have a minimum life expectancy of \>3 months.
* Have adequate organ function, as defined below:
* Hematology:
* Absolute neutrophil count ≥1.5 × 10\^9/L.
* Platelet count ≥100 × 10\^9/L.
* Hemoglobin ≥90 g/L or 5.6 mmol/L.
* Liver function:
* Total bilirubin ≤1.5 × upper limit of normal (ULN).
* With Gilbert's syndrome total bilirubin \<3 mg/dL and direct bilirubin ≤ULN. Note, Gilbert's syndrome must be documented appropriately as past medical history.
* Participants without liver metastasis alanine aminotransferase and aspartate aminotransferase ≤2 × ULN.
* Participants with liver metastasis alanine aminotransferase and aspartate aminotransferase ≤5 × ULN.
* Albumin ≥3.0 g/dL.
* Renal function: Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min. Cockcroft-Gault formula.
* Qualitative urine protein ≤1+. If qualitative urine protein ≥2+, a 24-hour urine protein quantitative test is required. If the 24-hour urine protein result is \<1 g, the participant can be enrolled.
* Coagulation function: International normalized ratio or prothrombin time and activated partial thromboplastin time ≤1.5 × ULN unless the participant is receiving anticoagulation therapy as long as prothrombin or activated partial thromboplastin is within therapeutic range of intended use of anticoagulant.
* Are women of childbearing potential (WOCBP) who have a negative serum beta-human chorionic gonadotropin test at screening and before each IMP dose. Women born female that are postmenopausal (defined as 12 months with no menses without an alternative medical cause) or permanently sterilized (verified by medical records) will not be considered WOCBP and therefore will not be required to undergo pregnancy testing.
* Are WOCBP who agree to practice a highly effective form of contraception and to require their male sexual partners to use barrier contraception methods (preferably condoms), starting at Screening and continuously until 6 months after receiving the last study treatment.
* Are men who are sexually active with a partner born female and have not had a vasectomy 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 Screening Period and continuously until 6 months after receiving the last dose of IMP.
* Are WOCBP who agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study, starting at the Screening Period and continuously 6 months after receiving the last dose of IMP.
* Are men who are willing to refrain from sperm donation, starting at the Screening Period and continuously until 6 months after the last dose of IMP.
Exclusion Criteria
* 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.
* 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.
* Have histologically or cytologically confirmed SCLC with combined histologies.
* Have received any of the following therapies or drugs within the noted time intervals prior to the initiation of study treatment:
* Within 2 weeks: small molecule targeted agents with half-life of \<7 days; or radiation not involving the thoracic cavity; local radiation for brain lesion is allowed; local radiation for bone lesions is allowed.
* Within 4 weeks: radiation involving the thoracic cavity; small molecule targeted agents with half-life of ≥7 days; monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies.
* Participants who received prior treatment with a PDL-1/VEGF bispecific antibody.
* Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 10 days prior to the initiation of study treatment. Note: The following are allowed: 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 been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of the study treatment.
* Received broad-spectrum intravenous antibiotics therapy within 2 weeks prior to initiation of study treatment.
* Use of any non-study IMP within 3 weeks before initiation of study treatment in this study or ongoing participation in the active treatment phase of another interventional clinical study.
* 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.
* Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
* Have the following central nervous system metastases:
* Participants with untreated brain metastases that are symptomatic or large (e.g., \>2 cm).
* Participants who received treatment for central nervous system metastases are not neurologically stable or still on steroids 10 days before initiating IMP of this study.
* Participants with known leptomeningeal metastases.
* Have active autoimmune disease or history of autoimmune diseases with anticipated relapse (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for those with clinically stable autoimmune thyroid disease or type 1 diabetes.
* Have had other malignant tumors within 2 years prior to the study treatment are not allowed. Except for those: who have been cured with local treatment (such as basal cell or squamous cell carcinoma of the skin, superficial or non-invasive bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, papillary carcinoma of thyroid and early stage prostate cancer).
* Have any of the following heart conditions within 6 months prior to the study treatment:
* Acute coronary syndrome, coronary artery bypass grafting, congestive heart failure, aortic dissection, stroke, or other Grade 3 and above cardiovascular and cerebrovascular events.
* New York Heart Association functional classification ≥II heart failure or left ventricular ejection fraction \<50%.
* Those who have ventricular arrhythmias requiring clinical intervention, second- to third-degree atrioventricular block, or congenital long QT syndrome. Participants with treated cardiac arrythmia/atrial fibrillation are allowed.
* Mean QT interval corrected by Fridericia's method \>480 ms (the electrocardiogram can be repeated at the discretion of the investigator).
* Use of cardiac pacemaker.
* Cardiac troponin I or T \>2 x ULN.
* Have any of the following hypertension or diabetic conditions prior to initiation of study treatment:
* Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg) while on antihypertensive medicine.
* Those with a history of hypertensive crisis or hypertensive encephalopathy.
* Poorly controlled diabetes (fasting blood glucose ≥13.3 mmol/L \[240 mg/dL\]).
* Have serious non-healing wounds, ulcers, or bone fractures. This includes history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess for which an interval of 6 months must pass before enrollment into this study. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation.
* Participants with evidence of major coagulation disorders or other significant risks of hemorrhage such as:
* History of intracranial or intraspinal hemorrhage.
* Tumor lesions invading large vessels and with significant risk of bleeding
* Had clinically significant hemoptysis or tumor hemorrhage within 1 month prior to the initiation of study treatment.
* Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters (e.g., PleurX) are allowed. However, participants who are clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis or with indwelling catheters, e.g., PleurX) are allowed.
* Participants with a history of serious Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior immunotherapy. Participants with a history of Grade ≥3 irAEs that did not lead to discontinuation of a prior immunotherapy but fully recovered may be enrolled per investigator's discretion. The investigator may request sponsor guidance in such cases.
* Have a known or suspected hypersensitivity to the study treatments including any active ingredient or excipients thereof.
* Have known human immunodeficiency virus infection or known acquired immunodeficiency syndrome, with the following exceptions:
* Participants with cluster of differentiation 4 (CD4)+ T-cell (CD4+) counts ≥350 cells/µL per local laboratory should generally be eligible for the study.
* Participants who have not had an opportunistic infection within the past 12 months.
* Have a 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). Individuals with positive serology must have hepatitis B virus viral load below the limit of quantification.
* Have an active hepatitis C virus infection; individuals who have completed curative antiviral treatment with hepatitis C virus viral load below the limit of quantification are allowed.
* Participants with AEs from prior antitumor therapy whose AE(s) have not returned to Grade 1 (graded by NCI CTCAE v5.0 criteria) or below (unless the investigator determines that certain AEs pose no safety risk to participants, such as hair loss, Grade 2 peripheral neuropathy or stable hypothyroidism under hormone replacement therapy) are not eligible for the study.
* Have superior vena cava syndrome or symptoms of spinal cord compression.
* Those with active, or a history of, pneumonitis requiring treatment with steroids, or has active, or a history of, interstitial lung disease. Those with a history of pulmonary fibrosis, or currently diagnosed with severe lung diseases such as interstitial pneumonia, pneumoconiosis, chemical pneumonitis, or any other condition resulting in significant impairment in lung function. Exception: Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable.
* Have active tuberculosis.
* Have underlying condition(s) that may increase the risk of the combination treatment or complicate the interpretation of AEs, as judged by the investigator, or other scenarios in which the investigator consider the participant as not eligible for the study.
* 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. This includes all sponsor, study site, or third party (e.g., contract research organization, vendor) personnel directly involved in the conduct of the sudy and their family members or dependents, as well as all study site personnel otherwise supervised by the investigator.
* 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.
* Have histologically or cytologically confirmed SCLC with combined histologies.
* Have received any of the following therapies or drugs within the noted time intervals prior to the initiation of study treatment:
* Within 2 weeks: small molecule targeted agents with half-life of \<7 days; or radiation not involving the thoracic cavity; local radiation for brain lesion is allowed; local radiation for bone lesions is allowed.
* Within 4 weeks: radiation involving the thoracic cavity; small molecule targeted agents with half-life of ≥7 days; monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies.
* Participants who received prior treatment with a PDL-1/VEGF bispecific antibody.
* Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 10 days prior to the initiation of study treatment. Note: The following are allowed: 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 been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of the study treatment.
* Received broad-spectrum intravenous antibiotics therapy within 2 weeks prior to initiation of study treatment.
* Use of any non-study IMP within 3 weeks before initiation of study treatment in this study or ongoing participation in the active treatment phase of another interventional clinical study.
* 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.
* Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
* Have the following central nervous system metastases:
* Participants with untreated brain metastases that are symptomatic or large (e.g., \>2 cm).
* Participants who received treatment for central nervous system metastases are not neurologically stable or still on steroids 10 days before initiating IMP of this study.
* Participants with known leptomeningeal metastases.
* Have active autoimmune disease or history of autoimmune diseases with anticipated relapse (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for those with clinically stable autoimmune thyroid disease or type 1 diabetes.
* Have had other malignant tumors within 2 years prior to the study treatment are not allowed. Except for those: who have been cured with local treatment (such as basal cell or squamous cell carcinoma of the skin, superficial or non-invasive bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, papillary carcinoma of thyroid and early stage prostate cancer).
* Have any of the following heart conditions within 6 months prior to the study treatment:
* Acute coronary syndrome, coronary artery bypass grafting, congestive heart failure, aortic dissection, stroke, or other Grade 3 and above cardiovascular and cerebrovascular events.
* New York Heart Association functional classification ≥II heart failure or left ventricular ejection fraction \<50%.
* Those who have ventricular arrhythmias requiring clinical intervention, second- to third-degree atrioventricular block, or congenital long QT syndrome. Participants with treated cardiac arrythmia/atrial fibrillation are allowed.
* Mean QT interval corrected by Fridericia's method \>480 ms (the electrocardiogram can be repeated at the discretion of the investigator).
* Use of cardiac pacemaker.
* Cardiac troponin I or T \>2 x ULN.
* Have any of the following hypertension or diabetic conditions prior to initiation of study treatment:
* Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg) while on antihypertensive medicine.
* Those with a history of hypertensive crisis or hypertensive encephalopathy.
* Poorly controlled diabetes (fasting blood glucose ≥13.3 mmol/L \[240 mg/dL\]).
* Have serious non-healing wounds, ulcers, or bone fractures. This includes history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess for which an interval of 6 months must pass before enrollment into this study. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation.
* Participants with evidence of major coagulation disorders or other significant risks of hemorrhage such as:
* History of intracranial or intraspinal hemorrhage.
* Tumor lesions invading large vessels and with significant risk of bleeding
* Had clinically significant hemoptysis or tumor hemorrhage within 1 month prior to the initiation of study treatment.
* Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters (e.g., PleurX) are allowed. However, participants who are clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis or with indwelling catheters, e.g., PleurX) are allowed.
* Participants with a history of serious Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior immunotherapy. Participants with a history of Grade ≥3 irAEs that did not lead to discontinuation of a prior immunotherapy but fully recovered may be enrolled per investigator's discretion. The investigator may request sponsor guidance in such cases.
* Have a known or suspected hypersensitivity to the study treatments including any active ingredient or excipients thereof.
* Have known human immunodeficiency virus infection or known acquired immunodeficiency syndrome, with the following exceptions:
* Participants with cluster of differentiation 4 (CD4)+ T-cell (CD4+) counts ≥350 cells/µL per local laboratory should generally be eligible for the study.
* Participants who have not had an opportunistic infection within the past 12 months.
* Have a 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). Individuals with positive serology must have hepatitis B virus viral load below the limit of quantification.
* Have an active hepatitis C virus infection; individuals who have completed curative antiviral treatment with hepatitis C virus viral load below the limit of quantification are allowed.
* Participants with AEs from prior antitumor therapy whose AE(s) have not returned to Grade 1 (graded by NCI CTCAE v5.0 criteria) or below (unless the investigator determines that certain AEs pose no safety risk to participants, such as hair loss, Grade 2 peripheral neuropathy or stable hypothyroidism under hormone replacement therapy) are not eligible for the study.
* Have superior vena cava syndrome or symptoms of spinal cord compression.
* Those with active, or a history of, pneumonitis requiring treatment with steroids, or has active, or a history of, interstitial lung disease. Those with a history of pulmonary fibrosis, or currently diagnosed with severe lung diseases such as interstitial pneumonia, pneumoconiosis, chemical pneumonitis, or any other condition resulting in significant impairment in lung function. Exception: Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable.
* Have active tuberculosis.
* Have underlying condition(s) that may increase the risk of the combination treatment or complicate the interpretation of AEs, as judged by the investigator, or other scenarios in which the investigator consider the participant as not eligible for the study.
* 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. This includes all sponsor, study site, or third party (e.g., contract research organization, vendor) personnel directly involved in the conduct of the sudy and their family members or dependents, as well as all study site personnel otherwise supervised by the investigator.
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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BioNTech SE
INDUSTRY
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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BioNTech Responsible Person
Role: STUDY_DIRECTOR
BioNTech SE
Locations
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Alaska Oncology and Hematology, LLC
Anchorage, Alaska, United States
Site Status
Valkyrie Clinical Trials
Los Angeles, California, United States
Site Status
Clermont Oncology Center
Clermont, Florida, United States
Site Status
Hematology Oncology Associates of Treasure Coast
Port Saint Lucie, Florida, United States
Site Status
Tallahassee Memorial Physician Partners - Cancer & Hematology Specialists
Tallahassee, Florida, United States
Site Status
Carle Foundation Hospital d/b/a Carle Cancer Center
Urbana, Illinois, United States
Site Status
Fort Wayne Medical Oncology and Hematology, Inc
Fort Wayne, Indiana, United States
Site Status
University of Kentucky Chandler Medical Center (UKCMC) - Markey Cancer Center (Lucille P. Markey Cancer Center)
Lexington, Kentucky, United States
Site Status
Allina Health
Minneapolis, Minnesota, United States
Site Status
SSM Health Cancer Care - St. Clare
Fenton, Missouri, United States
Site Status
Nebraska Hematology-Oncology (NHO) - Lincoln
Lincoln, Nebraska, United States
Site Status
Clinical Research Alliance Inc
Westbury, New York, United States
Site Status
Haywood Infusion Center
Clyde, North Carolina, United States
Site Status
FirstHealth Outpatient Cancer Center
Pinehurst, North Carolina, United States
Site Status
The Christ Hospital Cancer Center
Cincinnati, Ohio, United States
Site Status
University of Tennessee Medical Center
Knoxville, Tennessee, United States
Site Status
Millenium Research & Clinical Development
Houston, Texas, United States
Site Status
SSM Health Cancer Care
Madison, Wisconsin, United States
Site Status
Lyell McEwin Hospital
Adelaide, , Australia
Site Status
St. Vincent's Hospital
Fitzroy, , Australia
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Peninsula Oncology Centre
Frankston, , Australia
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Royal North Shore Hospital
St Leonards, , Australia
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Westmead Hospital
Westmead, , Australia
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Chungbuk National University Hospital
Cheongju-si, , South Korea
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Yeungnam University Medical Center
Daegu, , South Korea
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National Cancer Center
Goyang-si, , South Korea
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Gachon University Gil Medical Center
Incheon, , South Korea
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Gyeongsang National University Hospital (GNUH)
Jinju, , South Korea
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Korea University Anam Hospital
Seoul, , South Korea
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Severance Hospital, Yonsei University Health System
Seoul, , South Korea
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The Catholic University of Korea Seoul St. Mary's Hospital
Seoul, , South Korea
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Ajou University Hospital
Suwon, , South Korea
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Baskent University Hospital Adana Dr Turgut Noyan Research Center
Adana, , Turkey (Türkiye)
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Medical Park Seyhan Hospital
Adana, , Turkey (Türkiye)
Site Status
Adana City Training and Research Hospital
Adana, , Turkey (Türkiye)
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Gulhane Egitim ve Arastirma Hastanesi
Ankara, , Turkey (Türkiye)
Site Status
Ankara Etlik Sehir Hastanesi
Ankara, , Turkey (Türkiye)
Site Status
Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital
Ankara, , Turkey (Türkiye)
Site Status
Hacettepe University Medical Faculty Oncology Hospital
Ankara, , Turkey (Türkiye)
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Memorial Ankara Hospital
Ankara, , Turkey (Türkiye)
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Liv Hospital
Ankara, , Turkey (Türkiye)
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Ankara City Hospital
Ankara, , Turkey (Türkiye)
Site Status
Gaziantep Sanko University Medical Faculty
Gaziantep, , Turkey (Türkiye)
Site Status
Koc Universitesi Hastanesi (Koc University Hospital)
Istanbul, , Turkey (Türkiye)
Site Status
Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi
Istanbul, , Turkey (Türkiye)
Site Status
Acibadem Adana Hastanesi
Istanbul, , Turkey (Türkiye)
Site Status
Yeditepe University Kosuyolu Hospital
Istanbul, , Turkey (Türkiye)
Site Status
Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
Istanbul, , Turkey (Türkiye)
Site Status
Medical Point Izmir Hospital
Izmir, , Turkey (Türkiye)
Site Status
Kocaeli Universitesi Tip Fakultesi
Kocaeli, , Turkey (Türkiye)
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Sakarya University - Faculty of Medicine
Sakarya, , Turkey (Türkiye)
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Namik Kemal University Hospital
Tekirdağ, , Turkey (Türkiye)
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Gazi University Medical Faculty
Yenimahalle, , Turkey (Türkiye)
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Queen Elizabeth Hospital Birmingham - University Hospitals Birmingham NHS Foundation Trust
Birmingham, , United Kingdom
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Velindre Hospital - Velindre NHS Trust
Cardiff, , United Kingdom
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Ninewells Hospital and Medical School - Tayside Health Board
Dundee, , United Kingdom
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Royal Devon and Exeter Hospital, Wonford - Royal Devon And Exeter NHS Foundation Trust
Exeter, , United Kingdom
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Huddersfield Royal Infirmary - Calderdale and Huddersfield NHS Foundation Trust
Huddersfield, , United Kingdom
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St James's University Hospital - Leeds Teaching Hospitals NHS Trust
Leeds, , United Kingdom
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Sarah Cannon Research Institute
London, , United Kingdom
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Northern Centre for Cancer Care,The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, , United Kingdom
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Nottingham University Hospitals NHS Trust
Nottingham, , United Kingdom
Site Status
Royal Preston Hospital - Lancashire Teaching Hospitals NHS Foundation Trust
Preston, , United Kingdom
Site Status
Royal Stoke University Hospital - University Hospitals of North Midlands NHS Trust
Stoke-on-Trent, , United Kingdom
Site Status
Countries
Review the countries where the study has at least one active or historical site.
United States
Australia
South Korea
Turkey (Türkiye)
United Kingdom
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
BNT327-01
Identifier Type: -
Identifier Source: org_study_id