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RecruitingInterventionalPhase 2/Phase 3

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

NCT ID: NCT06712316Sponsor: BioNTech SELast updated: 2026-05-22

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 pumitamig (BNT327) plus chemotherapy for the Phase 2 part of each substudy. 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 IDMC 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.

Arms & interventions

  • DrugPumitamig

    Intravenous infusion

  • DrugPembrolizumab

    Intravenous infusion

  • DrugCarboplatin

    Intravenous infusion

  • DrugPemetrexed

    Intravenous infusion

  • DrugPaclitaxel

    Intravenous infusion

Outcome measures

Primary

  • 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

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

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

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

    For substudies A and B.

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

  • Phase 2 - Objective response rate (ORR)

    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.

    Time frame: Up to approximately 2 years

  • Phase 2 - Best percentage change from baseline in tumor size

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

    Time frame: Up to approximately 2 years

  • Phase 3 - Progression free survival (PFS) assessed by blinded independent central review (BICR)

    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.

    Time frame: Up to approximately 5 years

Secondary

  • Phase 3 - Overall survival (OS)

    Time frame: Up to approximately 5 years

  • Phase 2 - Duration of Response (DOR)

    Time frame: Up to approximately 2 years

  • Phase 2 - Disease Control Rate (DCR)

    Time frame: Up to approximately 2 years

  • Phase 3 - PFS assessed by investigator

    Time frame: Up to approximately 5 years

  • Phase 3 - ORR

    Time frame: Up to approximately 2 years

  • Phase 3 - PFS rate as assessed by BICR

    Time frame: At 6, 12, and 18 months

  • Phase 3 - PFS rate as assessed by investigator

    Time frame: At 6, 12, and 18 months

  • Phase 3 - OS rate

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

  • 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)

    Time frame: Up to approximately 5 years

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

    Time frame: Up to approximately 5 years

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

    Time frame: Up to approximately 5 years

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

    Time frame: Up to approximately 5 years

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

    Time frame: Up to approximately 5 years

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

    Time frame: Up to approximately 5 years

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

    Time frame: Up to approximately 5 years

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

    Time frame: Up to approximately 5 years

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

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

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

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

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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. Key Exclusion Criteria: * Have histologically or cytologically confirmed NSCLC with small-cell lung cancer histologic or neuroendocrine 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 neo-adjuvant/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). * Have superior vena cava syndrome or symptoms of spinal cord compression. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study locations (36)

Alaska Oncology and Hematology, LLC

Anchorage, Alaska, 99508

Recruiting

John Muir Clinical Research Center

Concord, California, 94520

Recruiting

University Of California - San Diego Moores Cancer Center

La Jolla, California, 92093

Recruiting

Clermont Oncology Center

Clermont, Florida, 34711

Recruiting

Mid Florida Cancer Centers

Orange City, Florida, 32763

Recruiting

Cleveland Clinic Florida - Martin North Hospital

Stuart, Florida, 34994

Recruiting

H. Lee Moffit Cancer center and research institute

Tampa, Florida, 33612

Recruiting

Cleveland Clinic Weston Hospital

Weston, Florida, 33331

Recruiting

Fort Wayne Medical Oncology and Hematology, Inc.

Fort Wayne, Indiana, 46845

Recruiting

Physicians Clinic of Iowa

Cedar Rapids, Iowa, 52401-2112

Recruiting

Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242

Recruiting

Baptist Health Hardin

Elizabethtown, Kentucky, 42701

Recruiting

Frederick Health Hospital- James M Stockman Cancer Institute

Frederick, Maryland, 21704

Recruiting

Missouri Cancer Associates

Columbia, Missouri, 65201

Recruiting

SSM Health Cancer Care - St. Clare

Fenton, Missouri, 63026

Recruiting

Mary Lanning Healthcare (MLH) - Morrison Cancer Center (MCC)

Hastings, Nebraska, 68901-4470

Recruiting

Astera Cancer Care

East Brunswick, New Jersey, 08816

Recruiting

Summit Medical Group PA

Florham Park, New Jersey, 07932

Recruiting

The Valley Hospital - Valley Health System - The Robert and Audrey Luckow Pavilion

Paramus, New Jersey, 07652

Recruiting

Suny-Stony Brook University Cancer Center

Stony Brook, New York, 11794-9446

Recruiting

White Plains Hospital

White Plains, New York, 10601

Recruiting

Fletcher Hospital, Inc. dba AdventHealth Hendersonville

Hendersonville, North Carolina, 28792

Recruiting

Gabrail Cancer Center Research

Canton, Ohio, 44718

Recruiting

The Christ Hospital Cancer Center

Cincinnati, Ohio, 45219

Recruiting

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219

Recruiting

The Cleveland Clinic Cancer Center At Fairview Hospital, Moll Pavilion

Cleveland, Ohio, 44111

Recruiting

Cleveland Clinic

Cleveland, Ohio, 44195-0001

Recruiting

Kettering Medical Center

Kettering, Ohio, 45429

Recruiting

Cleveland Clinic - Hillcrest Hospital

Mayfield Heights, Ohio, 44124

Recruiting

INTEGRIS Cancer Institute of Oklahoma

Oklahoma City, Oklahoma, 73109

Recruiting

University of Tennessee Medical Center

Knoxville, Tennessee, 37920

Recruiting

Baptist Cancer Center

Memphis, Tennessee, 38120

Recruiting

Millennium Research and Clinical Development, LLC

Houston, Texas, 77090

Active Not Recruiting

Virginia Cancer Specialists

Fairfax, Virginia, 22031

Recruiting

VCU Massey Cancer Center

Richmond, Virginia, 23298

Recruiting

Shenandoah Oncology

Winchester, Virginia, 22601

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