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RecruitingInterventionalPhase 3

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

NCT ID: NCT06712355Sponsor: BioNTech SELast updated: 2026-06-01

Summary

This is a Phase III, multisite, randomized, double-blinded study to investigate pumitamig (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

There are two stages in this study: Stage 1 will have two treatment arms and one control arm, and Stage 2 will have a treatment arm and a control arm. The control arms in Stages 1 and 2 are the same. Each stage of 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). In Stage 1, eligible participants will be randomized (1:1:1) to the arms. In Stage 2, participants will then be randomized (1:1) to the arms. The randomization will be stratified based on the following factors: 1. Brain or liver metastases per investigator assessment (presence versus absence); 2. Smoking status (smoker versus never-smoker); and 3. Geography. Participants will be allowed to switch to cisplatin if carboplatin is not tolerated at the investigator's discretion.

Arms & interventions

  • DrugPumitamig

    Intravenous infusion

  • DrugAtezolizumab

    Intravenous infusion

  • DrugEtoposide

    Intravenous infusion and capsules

  • DrugCarboplatin (or cisplatin if carboplatin is not tolerated)

    Intravenous infusion

Outcome measures

Primary

  • Overall survival (OS)

    OS defined as the time from randomization to death from any cause.

    Time frame: Up to approximately 46 months

Secondary

  • Progression-free survival (PFS)

    Time frame: Up to approximately 46 months

  • Objective response rate (ORR)

    Time frame: Up to approximately 46 months

  • Duration of response (DOR)

    Time frame: Up to approximately 46 months

  • PFS rate based on investigator's assessment

    Time frame: At 6, 12, and 18 months

  • OS rate

    Time frame: At 6, 12, 18, and 24 months

  • Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs by relationship

    Time frame: From the first dose of study treatment to the 90-Day Follow-up Visit

  • Occurrence of dose delay, infusion interruption and discontinuation of study treatment due to TEAEs (including related TEAEs)

    Time frame: From first to last dose of study treatment, i.e., up to 2 years

  • 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)

    Time frame: Up to approximately 46 months

  • Change from baseline in EORTC QLQ-C30 physical functioning

    Time frame: Up to approximately 46 months

  • Change from baseline in coughing scale of the EORTC Quality-of-Life-Lung cancer 29 questionnaire (QLQ-LC29)

    Time frame: Up to approximately 46 months

  • Change from baseline in shortness of breath scale of the EORTC QLQ-LC29

    Time frame: Up to approximately 46 months

  • Change from baseline in coughed up blood item of the EORTC QLQ-LC29

    Time frame: Up to approximately 46 months

  • Change from baseline in Functional Assessment of Cancer Therapy-General overall bother item (FACT-GP5).

    Time frame: Up to approximately 46 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 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 chemotherapy, radiotherapy, 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 as defined in the protocol. 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 outside the thoracic cavity including whole brain radiation. Of note, other local radiation for brain lesions (not whole brain) is allowed; local radiation for bone lesions is allowed. Palliative bone radiation or brain stereotactic radiosurgery would not require a washout period, but participants should recover from radiotherapy-related toxicity. * 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 anti-vascular endothelial growth factor (VEGF) monoclonal antibody, or programmed death (ligand)-1 (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 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 (at a dosage greater than 10 mg/Day of prednisone or an equivalent dose of other corticosteroid) within 7 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 a serious or non-healing wound, or (incompletely healed) 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 a significant risk of hemorrhage (per investigator clinical judgment) as defined in the protocol. * Have superior vena cava syndrome or symptoms of spinal cord compression that requires urgent medical intervention. NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Study locations (32)

ACRC Arizona Clinical Research Center

Tucson, Arizona, 85715

Recruiting

Clermont Oncology Center

Clermont, Florida, 34711

Terminated

Cancer Care Centers of Brevard, Inc

Palm Bay, Florida, 32901

Recruiting

Illinois Cancer Specialists

Niles, Illinois, 60714

Recruiting

Fort Wayne Medical Oncology and Hematology, Inc

Fort Wayne, Indiana, 46804

Recruiting

McFarland Clinic

Ames, Iowa, 50010

Recruiting

Helen G. Nassif Community Cancer Center

Cedar Rapids, Iowa, 52403

Recruiting

Baptist Health Hardin Cancer Center

Elizabethtown, Kentucky, 42701

Recruiting

Frederick Health Hospital- James M Stockman Cancer Institute

Frederick, Maryland, 21704

Recruiting

Beth Israel Lahey Health - Lahey Hospital & Medical Center (LHMC), Lahey Clinic Medical Center

Burlington, Massachusetts, 01805

Recruiting

Baptist Cancer Center

Southaven, Mississippi, 38671

Recruiting

Washington University School of Medicine

St Louis, Missouri, 63110

Recruiting

Nebraska Hematology-Oncology (NHO)

Lincoln, Nebraska, 68506

Recruiting

Cornell University - NewYork-Presbyterian/Weill Cornell Medical Center

New York, New York, 10065

Recruiting

White Plains Hospital

White Plains, New York, 10601

Recruiting

Cleveland Clinic - Akron General Hematology & Oncology

Akron, Ohio, 44302

Recruiting

Cleveland Clinic Mercy Hospital Cancer Center

Canton, Ohio, 44708

Recruiting

The Christ Hospital Cancer Center

Cincinnati, Ohio, 45219

Recruiting

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106

Recruiting

The Cleveland Clinic Cancer Center at Fairview Hospital, Moll Pavilion

Cleveland, Ohio, 44111

Recruiting

Cleveland Clinic Foundation

Cleveland, Ohio, 44195-0001

Recruiting

Kettering Medical Center

Kettering, Ohio, 45429

Recruiting

Cleveland Clinic - Hillcrest Hospital

Mayfield Heights, Ohio, 44124

Recruiting

St. Luke's Physician Group - St. Luke's Cancer Care Associates

Fountain Hill, Pennsylvania, 18015-1153

Recruiting

University of Tennessee Medical Center

Knoxville, Tennessee, 37920

Recruiting

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting

Millennium Research and Clinical Development, LLC

Houston, Texas, 77090

Terminated

Texas Oncology Cancer Center

Sugar Land, Texas, 77479

Recruiting

Virginia Cancer Specialists

Fairfax, Virginia, 22031

Recruiting

Hematology Oncology Associates of Fredericksburg, Inc.

Fredericksburg, Virginia, 22408

Recruiting

Virginia Commonwealth University School of Medicine

Richmond, Virginia, 23298

Recruiting

Shenandoah Oncology

Winchester, Virginia, 22601

Recruiting
Safety and Efficacy of BNT327, an Investigational Therapy in Combination With Chemotherapy for Patients With Untreated Small-cell Lung Cancer | Cancerify