Safety, Efficacy, and Pharmacokinetics of BNT327 in Combination With Chemotherapy and Other Investigational Agents for Lung Cancer

NCT06712316
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Phase
Phase 2/Phase 3
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Recruitment status
Recruiting
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Participants
1,580
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Lead sponsor
BioNTech SE
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Start date
2025-01-07
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Number of sites
261
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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.
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Short title
Safety, Efficacy, and Pharmacokinetics of BNT327 in Combination With Chemotherapy and Other Investigational Agents for Lung Cancer
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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
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 2/Phase 3
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Study type
Interventional
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Completion date
2031-12-01
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First posted
2024-12-02
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Registry last updated
2026-08-13
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Primary completion date
2029-01-01
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Start date
2025-01-07
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Participants
1,580
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Participant count basis
Estimated
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Planned participants
1,580
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Protocol amendments
4
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Number of sites
261
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
BioNTech SE
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06712316
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ClinicalTrials.gov ID
NCT06712316
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Registry record
Open registry record
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Allocation
Randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. 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

    Timeframe: From the first dose of the investigational medicinal product (IMP) to the 90-day Follow-Up Visit

    For substudies A and B. AEs graded according to Common Terminology Criteria for Adverse Events (CTCAE v5.0) in the combination treatment regimen.

  2. Phase 2 - Occurrence of dose interruption, reduction, and discontinuation of IMP due to TEAEs (including related TEAEs)

    Timeframe: From the first dose of IMP to the 90-day Follow-Up Visit

    For substudies A and B.

  3. Phase 2 - Objective response rate (ORR)

    Timeframe: Up to approximately 2 years

    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.

  4. Phase 2 - Best percentage change from baseline in tumor size

    Timeframe: Up to approximately 2 years

    For substudies A and B. Based on investigator's tumor assessment according to RECIST v1.1.

  5. Phase 3 - Progression free survival (PFS) assessed by BICR

    Timeframe: Up to approximately 5 years

    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.

  1. Phase 3 - Overall survival (OS)

    Timeframe: Up to approximately 5 years

    For substudies A and B. OS defined as the time from randomization to death from any cause

  2. Phase 2 - Duration of Response (DOR)

    Timeframe: Up to approximately 2 years

    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.

  3. Phase 2 - Disease Control Rate (DCR)

    Timeframe: Up to approximately 2 years

    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.

  4. Phase 3 - PFS assessed by investigator

    Timeframe: Up to approximately 5 years

    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.

  5. Phase 3 - ORR

    Timeframe: Up to approximately 2 years

    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.

  6. Phase 3 - PFS rate as assessed by BICR

    Timeframe: At 6, 12, and 18 months

    For substudies A and B.

  7. Phase 3 - PFS rate as assessed by investigator

    Timeframe: At 6, 12, and 18 months

    For substudies A and B.

  8. Phase 3 - OS rate

    Timeframe: At 6, 12, 18, 24 months

    For substudies A and B.

  9. 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)

    Timeframe: Up to approximately 5 years

    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).

  10. Phase 3 - Change from baseline in EORTC QLQ-C30 physical functioning

    Timeframe: Up to approximately 5 years

    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 (e.g., high score for functional scale is high/healthy level of functioning.

  11. Phase 3 - Change from baseline in coughing scale of the EORTC lung cancer-specific quality-of-life questionnaire (QLQ-LC29)

    Timeframe: Up to approximately 5 years

    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.

  12. Phase 3 - Change from baseline in shortness of breath scale of the EORTC QLQ-LC29

    Timeframe: Up to approximately 5 years

    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.

  13. Phase 3 - Change from baseline in coughed up blood item of the EORTC QLQ-LC29

    Timeframe: Up to approximately 5 years

    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.

  14. Phase 3 - Change from baseline in fatigue domain score scale of the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ)

    Timeframe: Up to approximately 5 years

    For substudies A and B. The NSCLC-SAQ is a 7-item patient-reported outcome (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.

  15. Phase 3 - Change from baseline in pain domain score of the NSCLC-SAQ

    Timeframe: Up to approximately 5 years

    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.

  16. Phase 3 - Change from baseline in Functional Assessment of Cancer Therapy-General item 5 overall bother item (FACT-GP5)

    Timeframe: Up to approximately 5 years

    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.

  17. Phase 3 - Occurrence of TEAEs including Grade ≥3, serious, and fatal TEAEs by relationship

    Timeframe: From the first dose of IMP to the 90-day Follow-Up Visit

    For substudies A and B. AEs graded according to CTCAE v5.0.

  18. Phase 3 - Occurrence of dose interruption, reduction, and discontinuation of IMP due to TEAEs (including related TEAEs)

    Timeframe: From the first dose of IMP to the 90-day Follow-Up Visit

    For substudies A and B.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

Key Inclusion Criteria:

  • Have systemic treatment naive, 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, 9th edition.
  • 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 as defined in the protocol.

Key Exclusion Criteria:

  • Have histologically or cytologically confirmed NSCLC with small-cell lung cancer or neuroendocrine histologic component.

  • Have received any of the following therapies or drugs within the noted time intervals prior to study treatment:

    • Previous chemotherapy (platinum-based) or PD(L)-1 for treating NSCLC in either neoadjuvant/adjuvant or locally advanced/metastatic setting.
    • Participants who received prior treatment with anti-VEGF monoclonal antibody, or PD(L)-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 7 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 or non-healing wound, or (incompletely healed) 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 or esophageal and gastric varices. 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 significant risk of hemorrhage (per investigator clinical judgment).

  • Participants have superior vena cava syndrome or symptoms of spinal cord compression.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Sources for eligibility
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  • Birmingham Hematology and Oncology Associates LLC d/b/a Alabama OncologyBirmingham, United StatesRecruiting
  • Alaska Oncology and Hematology, LLCAnchorage, United StatesRecruiting
  • John Muir Clinical Research CenterConcord, United StatesRecruiting
  • University Of California - San Diego Moores Cancer CenterLa Jolla, United StatesRecruiting
  • Clermont Oncology CenterClermont, United StatesRecruiting
  • Mid Florida Cancer CentersOrange City, United StatesRecruiting
  • Cleveland Clinic Florida - Martin North HospitalStuart, United StatesRecruiting
  • H. Lee Moffit Cancer center and research instituteTampa, United StatesRecruiting
  • Cleveland Clinic Weston HospitalWeston, United StatesRecruiting
  • Fort Wayne Medical Oncology and Hematology, Inc.Fort Wayne, United StatesRecruiting
  • Physicians Clinic of IowaCedar Rapids, United StatesRecruiting
  • Holden Comprehensive Cancer Center, University of Iowa Hospitals and ClinicsIowa City, United StatesRecruiting
  • Baptist Health HardinElizabethtown, United StatesRecruiting
  • Frederick Health Hospital- James M Stockman Cancer InstituteFrederick, United StatesRecruiting
  • Missouri Cancer AssociatesColumbia, United StatesRecruiting
  • SSM Health Cancer Care - St. ClareFenton, United StatesRecruiting
  • Mary Lanning Healthcare (MLH) - Morrison Cancer Center (MCC)Hastings, United StatesRecruiting
  • Astera Cancer CareEast Brunswick, United StatesRecruiting
  • Summit Medical Group PAFlorham Park, United StatesRecruiting
  • The Valley Hospital - Valley Health System - The Robert and Audrey Luckow PavilionParamus, United StatesRecruiting
  • Suny-Stony Brook University Cancer CenterStony Brook, United StatesRecruiting
  • White Plains HospitalWhite Plains, United StatesRecruiting
  • Fletcher Hospital, Inc. dba AdventHealth HendersonvilleHendersonville, United StatesRecruiting
  • Gabrail Cancer Center ResearchCanton, United StatesRecruiting
  • The Christ Hospital Cancer CenterCincinnati, United StatesRecruiting

And 236 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2024-515764-31-00
Sources for references
clinicaltrials.gov

Related records

Drugs (4)

Collaborators (1)

Lead sponsors (1)

Conditions (2)

Targets (19)