Clinical trial NCT06712316: Safety, Effectiveness, and Pharmacokinetics of BNT327 in Combination With Chemotherapy and Other Investigational Agents for Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Non-small Cell Lung Cancer
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
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
Collaborators: name: Biotheus Inc.
First posted: 2024-12-02
Enrollment: 982
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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 decide 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 parts of both substudies, an independent data monitoring committee (IDMC) will be established as needed to provide independent review of the data during the study.

The sponsor may decide not to perform or stop recruiting participants in the Phase 2 part of the study depending on data generated in the BNT327-01 (NCT06449209) and BNT327-02 (NCT06449222) studies. The sponsor may also choose not to continue all substudies.

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 EGFR mutation or anaplastic lymphoma kinase 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 (ECOG) 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.

Primary outcomes:
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
timeFrame: From the first dose of the investigational medicinal product (IMP) to the 90-day Follow-Up Visit
measure: 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
measure: Phase 2 - Objective response rate (ORR) - unconfirmed
timeFrame: Up to approximately 2 years
measure: Phase 2 - Best percentage change from baseline in tumor size
timeFrame: Up to approximately 2 years
measure: Phase 3 - Progression free survival (PFS) assessed by blinded independent central review (BICR)
timeFrame: Up to approximately 5 years
measure: Phase 3 - Overall survival (OS)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Phase 2 - ORR - confirmed
timeFrame: Up to approximately 2 years
measure: Phase 2 - Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Phase 2 - Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Phase 3 - PFS assessed by investigator
timeFrame: Up to approximately 5 years
measure: Phase 3 - ORR assessed by BICR and by the investigator
timeFrame: Up to approximately 2 years
measure: Phase 3 - DOR assessed by BICR and by the investigator
timeFrame: Up to approximately 2 years
measure: Phase 3 - DCR assessed by BICR and by the investigator
timeFrame: Up to approximately 2 years
measure: Phase 3 - PFS rate as assessed by BICR
timeFrame: At 6, 12, and 18 months
measure: Phase 3 - PFS rate as assessed by investigator
timeFrame: At 6, 12, and 18 months
measure: Phase 3 - OS rate
timeFrame: At 6, 12, 18, 24 months
measure: Phase 3 - Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life-Core 30 Questionnaire (QLQ-C30)
timeFrame: Up to approximately 5 years
measure: Phase 3 - Change from baseline in EORTC Lung Cancer-Specific QoL Questionnaire (QLC-LC29)
timeFrame: Up to approximately 5 years
measure: Phase 3 - Change from baseline in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score and domain score
timeFrame: Up to approximately 5 years
measure: 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
measure: 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
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Oncology and Hematology, LLC
state: Alaska
city: Clermont
country: United States
facility: Clermont Oncology Center
state: Florida
city: Cedar Rapids
country: United States
facility: Physicians Clinic of Iowa
state: Iowa
city: Fenton
country: United States
facility: SSM Health Cancer Care - St. Clare
state: Missouri
city: Hendersonville
country: United States
facility: Fletcher Hospital, Inc. dba AdventHealth Hendersonville
state: North Carolina
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Houston
country: United States
facility: Millennium Research and Clinical Development, LLC
state: Texas
city: Cairns
country: Australia
facility: Cairns Hospital
city: Dubbo
country: Australia
facility: Dubbo Hospital
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
city: Kurralta Park
country: Australia
facility: Icon Cancer Centre Kurralta Park
city: St Albans
country: Australia
facility: Western Health Sunshine Hospital
city: Townsville
country: Australia
facility: ICON Cancer Care - Townsville
city: Wollongong
country: Australia
facility: Cancer Care Wollongong Pty Limited
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital (CNUH)
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Jinju-si
country: Korea, Republic of
facility: Gyeongsang National University Hospital (GNUH)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University Of Korea, St. Vincent's Hospital
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medicine Faculty
city: Ankara
country: Turkey
facility: Memorial Ankara Hospital
city: Ankara
country: Turkey
facility: Liv Hospital Ankara
city: Ankara
country: Turkey
facility: Ankara Bilkent City Hospital
city: Gaziantep
country: Turkey
facility: Gaziantep Sanko University Medical Faculty
city: Istanbul
country: Turkey
facility: Bezmialem Foundation University Medical Faculty
city: Istanbul
country: Turkey
facility: Yeditepe University Kosuyolu Hospital
city: Kadıköy
country: Turkey
facility: Goztepe Prof. Dr. Suleyman Yalcin City Hospital
city: Kecioren
country: Turkey
facility: Gulhane Training and Research Hospital
city: Kocaeli
country: Turkey
facility: Kocaeli Universitesi Tip Fakultesi
city: Kucukcekmece
country: Turkey
facility: Medical Park Florya Hospital
city: Sakarya
country: Turkey
facility: Sakarya University - Faculty of Medicine
city: Samsun
country: Turkey
facility: Ondokuz Mayis University Health Practice and Research Hospital
city: Seyhan
country: Turkey
facility: Acibadem Adana Hospital
city: Seyhan
country: Turkey
facility: Medical Park Seyhan Hospital
city: Yenimahalle
country: Turkey
facility: Gazi University Faculty of Medicine
city: Cardiff
country: United Kingdom
facility: Velindre NHS Trust, Velindre Cancer Centre
city: Cottingham
country: United Kingdom
facility: Hull University Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: University College Hospital
city: Oxford
country: United Kingdom
facility: Cancer And Haematology Centre-The Churchill Hospital-Oxford University Hospitals
city: Preston
country: United Kingdom
facility: Royal Preston Hospital - Lancashire Teaching Hospitals NHS Foundation Trust
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: BioNTech SE
name: BioNTech Responsible Person
role: STUDY_DIRECTOR
References: