Clinical trial NCT06712355: Safety and Effectiveness of BNT327, an Investigational Therapy in Combination With Chemotherapy for Patients With Untreated Small-cell Lung Cancer
Official title: A Phase III, Multisite, Double-blinded Randomized Trial of BNT327 in Combination With Chemotherapy (Etoposide/Carboplatin) Compared to Atezolizumab in Combination With Chemotherapy (Etoposide/Carboplatin) in Participants With First-line Extensive-stage Small-cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Extensive-stage Small-cell Lung Cancer
Keywords: First-line ES-SCLC
SCLC
Immunotherapy in combination with chemotherapy
Untreated
Bispecific antibody
Programmed death-ligand 1 (PD-L1)
Vascular endothelial growth factor (VEGF) A
Immunotherapy
Combination with other investigational agents
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
Collaborators: name: Biotheus Inc.
First posted: 2024-12-02
Enrollment: 439
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase III, multisite, randomized, double-blinded study to investigate BNT327 combined with chemotherapy (etoposide/carboplatin) compared to atezolizumab combined with chemotherapy (etoposide/carboplatin) for the treatment of participants with previously untreated extensive-stage small-cell lung cancer (ES-SCLC).

Detailed description: The study consists of a screening period (up to 21 days), an induction period followed by a maintenance period (until confirmed disease progression, intolerable toxicity, participant withdrawal, study termination or up to 2 years \[whichever occurs first\]), and a follow-up (FU) period for all participants (2 safety FU visits and survival FU visits).

Eligible patients will be randomized (1:1:1) to the treatment arms (Arm 1, Arm 2, and Arm 3), until one arm stops accrual. Participants will then be randomized (1:1) in the remaining two treatment arms (Arm 1 and Arm 2 or Arm 3). The randomization will be stratified based on the following factors:

1. Brain metastases per investigator assessment;
2. Liver metastases per investigator assessment; and
3. Geography.

Eligibility criteria: Inclusion Criteria:

* Have histologically or cytologically confirmed ES-SCLC (using the AJCC \[American Joint Committee on Cancer\] tumor node metastasis staging system combined with Veterans Administration Lung Study Group \[VALG\]'s two stage classification scheme).

  * For AJCC tumor node metastasis 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.
* Have not had prior systemic therapy for ES-SCLC. However, participants with prior chemoradiotherapy or immunotherapy for limited-stage-SCLC must have been treated with curative intent and had a treatment-free interval of at least 6 months after the last systemic anticancer treatment including chemotherapy, radiotherapy, immunotherapy, or chemoradiotherapy before diagnosis of ES-SCLC to be eligible.
* 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 hematologic and organ function.

Exclusion Criteria:

* 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 study treatment:

  * Within 2 weeks: small molecule agents with half-life of \<7 days; radiation not involving the thoracic cavity; local radiation for brain lesions 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.
  * Have received prior treatment with a programmed death (ligand)-1 (PD\[L\]-1)/vascular endothelial growth factor (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: 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 the following central nervous system metastases:

  * Participants with untreated brain metastases that are symptomatic or large (e.g., greater than 2 cm).
  * Participants with treated central nervous system (CNS) metastases who are not neurologically stable or on steroids within 10 days before initiating study treatment of this study.
  * Participants with known leptomeningeal metastases.
* Have uncontrolled hypertension or poorly controlled diabetes prior to study treatment.
* Have serious non-healing wound, ulcer, or bone fracture. This includes history of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess for which an interval of 6 months must pass before study entry. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation.
* Have 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 study treatment.
* Have superior vena cava syndrome or symptoms of spinal cord compression.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: Up to approximately 39 months
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 39 months
measure: Objective response rate (ORR)
timeFrame: Up to approximately 39 months
measure: PFS rate based on investigator's assessment
timeFrame: At 6, 12, and 18 months
measure: OS rate
timeFrame: At 6, 12, 18, and 24 months
measure: Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs by relationship
timeFrame: From the first dose of study treatment to the 90-Day Follow-up Visit
measure: Occurrence of dose delay, infusion interruption and discontinuation of study treatment due to TEAEs (including related TEAEs)
timeFrame: From first to last dose of study treatment, i.e., up to 2 years
measure: Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life Core 30 questionnaire (QLQ-C30) Global Health status/Quality-of-Life score (Items 29 and 30)
timeFrame: Up to approximately 39 months
measure: Change from baseline in EORTC QLQ-C30 physical functioning
timeFrame: Up to approximately 39 months
measure: Change from baseline in coughing scale of the EORTC quality-of-life-Lung cancer 29 questionnaire (QLQ-LC29)
timeFrame: Up to approximately 39 months
measure: Change from baseline in shortness of breath scale of the EORTC QLQ-LC29
timeFrame: Up to approximately 39 months
measure: Change from baseline in coughed up blood item of the EORTC QLQ-LC29
timeFrame: Up to approximately 39 months
measure: Change from baseline in fatigue domain score scale of the NSCLC-SAQ
timeFrame: Up to approximately 39 months
measure: Change from baseline in pain domain score of the Non-Small-Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ)
timeFrame: Up to approximately 39 months
Other outcomes:
Locations:
city: Clermont
country: United States
facility: Clermont Oncology Center
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc
state: Indiana
city: Lincoln
country: United States
facility: Nebraska Hematology-Oncology (NHO)
state: Nebraska
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: Fredericksburg
country: United States
facility: Hematology Oncology Associates of Fredericksburg, Inc.
state: Virginia
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
city: Kurralta Park
country: Australia
facility: Icon Cancer Centre Kurralta Park
city: Leeds
country: United Kingdom
facility: St James's University Hospital - Leeds Teaching Hospitals NHS Trust
Study officials:
affiliation: BioNTech SE
name: BioNTech Responsible Person
role: STUDY_DIRECTOR
References: