Brief Summary
This is a Phase 2/3, multisite, randomized, open-label study in participants with first-line non-small cell lung cancer (NSCLC).
This study includes two substudies (substudy A and substudy B) that will recruit participants according to histological subtypes due to differences in chemotherapy choice for standard-of-care and type of NSCLC.
This study includes two substudies (substudy A and substudy B) that will recruit participants according to histological subtypes due to differences in chemotherapy choice for standard-of-care and type of NSCLC.
Brief Title
Safety, Effectiveness, and Pharmacokinetics of BNT327 in Combination With Chemotherapy and Other Investigational Agents for Lung Cancer
Detailed Description
Each substudy contains a Phase 2 part followed by a Phase 3 part. Participants will be randomized to one of two dose levels of BNT327 plus chemotherapy for the Phase 2 part of each substudy. After the analysis of the Phase 2 data (efficacy, safety, and exposure-response), an internal review committee (IRC) will recommend whether participants will be treated with BNT327 at dose level 1 or 2 in the Phase 3 part of the substudies. After dose selection, the selected dose will be used for all participants in the study. For the Phase 3 part of both substudies, an independent data monitoring committee (IDMC) and a blinded Independent Central Review (BICR) will be established. The IDCM will provide independent review of the data during the study as needed and the BICR will review all available tumor assessment scans for all treated participants.
The planned study duration per study participant is up to 64 months.
The planned study duration per study participant is up to 64 months.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
+49 6131 9084
Central Contact Phone Ext
0
Central Contact Email
patients@biontech.de
Completion Date
Completion Date Type
Estimated
Conditions
Non-small Cell Lung Cancer
Eligibility Criteria
Key Inclusion Criteria:
* Have histologically or cytologically confirmed diagnosis of Stage IIIB or IIIC (who are not amenable to curative surgery or radiotherapy) or Stage IV NSCLC per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system, 8th edition without actionable epidermal growth factor receptor mutation or anaplastic lymphoma kinase (ALK) rearrangement.
* Have at least one measurable lesion as the targeted lesion based on RECIST v1.1. 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.
* Adequate organ function.
Key Exclusion Criteria:
* Have histologically or cytologically confirmed NSCLC with small-cell lung cancer histologic component.
* Have received any of the following therapies or drugs within the noted time intervals prior to study treatment:
* Participants who received prior treatment with anti-VEGF monoclonal antibody, or PD(L)-1/VEGF bispecific antibody or received platinum-based chemotherapy and/or anti-PD(L)-1 as part of adjuvant or neoadjuvant treatment
* Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 14 days prior to the initiation of study treatment. Note: 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) are allowed.
* Have uncontrolled hypertension or poorly controlled diabetic conditions prior to study treatment.
* Have a serious non-healing wound, ulcer, or bone fracture. This includes history (within 6 months prior to study entry) or risk of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing fistula/perforation.
* Participants with evidence of major coagulation disorders or other significant risks of hemorrhage.
* Have superior vena cava syndrome or symptoms of spinal cord compression.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
* Have histologically or cytologically confirmed diagnosis of Stage IIIB or IIIC (who are not amenable to curative surgery or radiotherapy) or Stage IV NSCLC per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system, 8th edition without actionable epidermal growth factor receptor mutation or anaplastic lymphoma kinase (ALK) rearrangement.
* Have at least one measurable lesion as the targeted lesion based on RECIST v1.1. 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.
* Adequate organ function.
Key Exclusion Criteria:
* Have histologically or cytologically confirmed NSCLC with small-cell lung cancer histologic component.
* Have received any of the following therapies or drugs within the noted time intervals prior to study treatment:
* Participants who received prior treatment with anti-VEGF monoclonal antibody, or PD(L)-1/VEGF bispecific antibody or received platinum-based chemotherapy and/or anti-PD(L)-1 as part of adjuvant or neoadjuvant treatment
* Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 14 days prior to the initiation of study treatment. Note: 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) are allowed.
* Have uncontrolled hypertension or poorly controlled diabetic conditions prior to study treatment.
* Have a serious non-healing wound, ulcer, or bone fracture. This includes history (within 6 months prior to study entry) or risk of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing fistula/perforation.
* Participants with evidence of major coagulation disorders or other significant risks of hemorrhage.
* Have superior vena cava syndrome or symptoms of spinal cord compression.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
* Have histologically or cytologically confirmed diagnosis of Stage IIIB or IIIC (who are not amenable to curative surgery or radiotherapy) or Stage IV NSCLC per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system, 8th edition without actionable epidermal growth factor receptor mutation or anaplastic lymphoma kinase (ALK) rearrangement.
* Have at least one measurable lesion as the targeted lesion based on RECIST v1.1. 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.
* Adequate organ function.
Inclusion/
* Have histologically or cytologically confirmed diagnosis of Stage IIIB or IIIC (who are not amenable to curative surgery or radiotherapy) or Stage IV NSCLC per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system, 8th edition without actionable epidermal growth factor receptor mutation or anaplastic lymphoma kinase (ALK) rearrangement.
* Have at least one measurable lesion as the targeted lesion based on RECIST v1.1. 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.
* Adequate organ function.
Inclusion/
Gender
All
Gender Based
false
Keywords
First-line treatment
Combination with chemotherapy
Combination with other investigational agents
Bispecific antibody
Programmed death-ligand 1 (PD-L1)
Vascular endothelial growth factor (VEGF) A
Immunotherapy
Programmed Death-1 monoclonal antibodies
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06712316
Org Class
Industry
Org Full Name
BioNTech SE
Org Study Id
BNT327-06
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase II/III, Multisite, Randomized Master Protocol for a Global Trial of BNT327 in Combination With Chemotherapy and Other Investigational Agents in First-line Non-small Cell Lung Cancer
Primary Outcomes
Outcome Description
For substudies A and B. AEs graded according to Common Terminology Criteria for Adverse Events (CTCAE v5.0) in the combination treatment regimen.
Outcome Measure
Phase 2 - Occurrence of treatment-emergent adverse events (TEAE) (including Grade ≥3), adverse events of special interest (AESIs), treatment-related TEAEs, treatment-emergent serious adverse events (SAE), and treatment-related treatment emergent SAEs
Outcome Time Frame
From the first dose of the investigational medicinal product (IMP) to the 90-day Follow-Up Visit
Outcome Description
For substudies A and B.
Outcome Measure
Phase 2 - Occurrence of dose interruption, reduction, and discontinuation of IMP due to TEAEs (including related TEAEs)
Outcome Time Frame
From the first dose of IMP to the 90-day Follow-Up Visit
Outcome Description
For substudies A and B. ORR is defined as the proportion of participants in whom a confirmed complete response (CR) or confirmed partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] based on the investigator's assessment) is observed as best overall response.
Outcome Measure
Phase 2 - Objective response rate (ORR)
Outcome Time Frame
Up to approximately 2 years
Outcome Description
For substudies A and B. Based on investigator's tumor assessment according to RECIST v1.1.
Outcome Measure
Phase 2 - Best percentage change from baseline in tumor size
Outcome Time Frame
Up to approximately 2 years
Outcome Description
For substudies A and B. PFS defined as the time from randomization to first documented tumor progression (progressive disease per RECIST v1.1), or death from any cause, whichever occurs first.
Outcome Measure
Phase 3 - Progression free survival (PFS) assessed by blinded independent central review (BICR)
Outcome Time Frame
Up to approximately 5 years
Outcome Description
For substudies A and B. OS defined as the time from randomization to death from any cause
Outcome Measure
Phase 3 - Overall survival (OS)
Outcome Time Frame
Up to approximately 5 years
Secondary Ids
Secondary Id
2024-515764-31-00
Secondary Outcomes
Outcome Description
For substudies A and B. DOR defined as the time from first objective response (CR or PR per RECIST v1.1) to first occurrence of objective tumor progression (progressive disease per RECIST v1.1) or death from any cause, whichever occurs first.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Phase 2 - Duration of Response (DOR)
Outcome Description
For substudies A and B. DCR defined as the proportion of participants in whom a confirmed CR or confirmed PR or stable disease (per RECIST v1.1, stable disease assessed at least 6 weeks after randomization) is observed as best overall response.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Phase 2 - Disease Control Rate (DCR)
Outcome Description
For substudies A and B. PFS defined as the time from randomization to first documented tumor progression (progressive disease per RECIST v1.1), or death from any cause, whichever occurs first.
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Phase 3 - PFS assessed by investigator
Outcome Description
For substudies A and B. ORR defined as the proportion of participants in whom a confirmed CR or confirmed PR (per RECIST v1.1) is observed as best overall response.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Phase 3 - ORR
Outcome Description
For substudies A and B.
Outcome Time Frame
At 6, 12, and 18 months
Outcome Measure
Phase 3 - PFS rate as assessed by BICR
Outcome Description
For substudies A and B.
Outcome Time Frame
At 6, 12, and 18 months
Outcome Measure
Phase 3 - PFS rate as assessed by investigator
Outcome Description
For substudies A and B.
Outcome Time Frame
At 6, 12, 18, 24 months
Outcome Measure
Phase 3 - OS rate
Outcome Description
For substudies A and B. The EORTC QLQ-C30 is the most widely used cancer-specific, health related QoL instrument containing a total of 30 items and measures 5 functional scales (physical, role, emotional, cognitive, and social), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global health status/QoL scale. All the scales and single-item measures range in score from 0 to 100 with a high scale score representing a higher response level (i.e., high score for global health status/QoL is high QoL: high score for symptom scale/item is high symptomatology or problems).
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Phase 3 - Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life-score 30 Questionnaire (QLQ-C30) global health status/Quality-of-Life (QoL) score (Items 29 and 30)
Outcome Description
For substudies A and B. The EORTC QLQ-C30 is the most widely used cancer-specific, health related QoL instrument containing a total of 30 items and measures 5 functional scales (physical, role, emotional, cognitive, and social), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global health status/QoL scale. All the scales and single-item measures range in score from 0 to 100 with a high scale score representing a higher response level (i.e., high score for functional scale is high/healthy level of functioning).
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Phase 3 - Change from baseline in EORTC QLQ-C30 physical functioning
Outcome Description
For substudies A and B. The EORTC QLQ-LC29 is a disease-specific supplementary health-related quality-of-life (HRQoL) questionnaire module to be employed in conjunction with the QLQ-C30. It comprises 29 items and measures five multi-item scales (coughing, shortness of breath, side effects, tumor progression/existential issues, surgery-related symptoms) and five single items (coughing up blood, pain in chest, arm/shoulder and other parts of the body, and weight loss). All the scales and single-item measures range in score from 0 to 100 with a high score for the scales and single items representing a high level of symptomatology or problems.
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Phase 3 - Change from baseline in coughing scale of the EORTC lung cancer-specific quality-of-life questionnaire (QLQ-LC29)
Outcome Description
For substudies A and B. The EORTC QLQ-LC29 is a disease-specific supplementary health-related quality-of-life (HRQoL) questionnaire module to be employed in conjunction with the QLQ-C30. It comprises 29 items and measures five multi-item scales (coughing, shortness of breath, side effects, tumor progression/existential issues, surgery-related symptoms) and five single items (coughing up blood, pain in chest, arm/shoulder and other parts of the body, and weight loss). All the scales and single-item measures range in score from 0 to 100 with a high score for the scales and single items representing a high level of symptomatology or problems.
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Phase 3 - Change from baseline in shortness of breath scale of the EORTC QLQ-LC29
Outcome Description
For substudies A and B. The EORTC QLQ-LC29 is a disease-specific supplementary health-related quality-of-life (HRQoL) questionnaire module to be employed in conjunction with the QLQ-C30. It comprises 29 items and measures five multi-item scales (coughing, shortness of breath, side effects, tumor progression/existential issues, surgery-related symptoms) and five single items (coughing up blood, pain in chest, arm/shoulder and other parts of the body, and weight loss). All the scales and single-item measures range in score from 0 to 100 with a high score for the scales and single items representing a high level of symptomatology or problems.
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Phase 3 - Change from baseline in coughed up blood item of the EORTC QLQ-LC29
Outcome Description
For substudies A and B. The NSCLC-SAQ is a 7-item patient-reported outcome measure for use in adults to assess symptoms of advanced non-small cell lung cancer. It contains five domains and accompanying items that were identified as symptoms of non small cell lung cancer: cough (1 item), pain (2), dyspnea (1), fatigue (2), and appetite (1). The (total) lowest score possible is 0, and the highest (total) score possible is 20. Higher scores indicate more severe symptoms.
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Phase 3 - Change from baseline in fatigue domain score scale of the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ)
Outcome Description
For substudies A and B. The NSCLC-SAQ is a 7-item PRO measure for use in adults to assess symptoms of advanced non-small cell lung cancer. It contains five domains and accompanying items that were identified as symptoms of non small cell lung cancer: cough (1 item), pain (2), dyspnea (1), fatigue (2), and appetite (1). The (total) lowest score possible is 0, and the highest (total) score possible is 20. Higher scores indicate more severe symptoms.
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Phase 3 - Change from baseline in pain domain score of the NSCLC-SAQ
Outcome Description
For substudies A and B. The FACT-G - Item GP5 (Version 4) is a single-item summary measure of the overall impact of treatment toxicity, based upon its association with the number and degree of AEs in clinical studies. The single-item GP5 ("I am bothered by side effects of treatment") is rated on a 5-point Likert scale ("not at all" to "very much") with a recall period of past 7 days.
Outcome Time Frame
Up to approximately 5 years
Outcome Measure
Phase 3 - Change from baseline in Functional Assessment of Cancer Therapy-General item 5 overall bother item (FACT-GP5).
Outcome Description
For substudies A and B. AEs graded according to CTCAE v5.0.
Outcome Time Frame
From the first dose of IMP to the 90-day Follow-Up Visit
Outcome Measure
Phase 3 - Occurrence of TEAEs including Grade ≥3, serious, and fatal TEAEs by relationship
Outcome Description
For substudies A and B.
Outcome Time Frame
From the first dose of IMP to the 90-day Follow-Up Visit
Outcome Measure
Phase 3 - Occurrence of dose interruption, reduction, and discontinuation of IMP due to TEAEs (including related TEAEs)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Prostate Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Endocrine System Cancers --- NEOPLASMS
Gastrointestinal (GI) Cancers --- NEOPLASMS
Gynecologic Cancers --- NEOPLASMS
Lung & Chest Cancers --- NEOPLASMS
Prostate Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
PEMBROLIZUMAB
CARBOPLATIN
PEMETREXED
PACLITAXEL
COORDINATION COMPLEXES
ORGANIC CHEMICALS
GUANINE
HYPOXANTHINES
PURINONES
PURINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS
GLUTAMATES
AMINO ACIDS, ACIDIC
AMINO ACIDS
AMINO ACIDS, PEPTIDES, AND PROTEINS
AMINO ACIDS, DICARBOXYLIC
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
DITERPENES
TERPENES