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
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
Study locations (36)
Alaska Oncology and Hematology, LLC
Anchorage, Alaska, 99508
John Muir Clinical Research Center
Concord, California, 94520
University Of California - San Diego Moores Cancer Center
La Jolla, California, 92093
Clermont Oncology Center
Clermont, Florida, 34711
Mid Florida Cancer Centers
Orange City, Florida, 32763
Cleveland Clinic Florida - Martin North Hospital
Stuart, Florida, 34994
H. Lee Moffit Cancer center and research institute
Tampa, Florida, 33612
Cleveland Clinic Weston Hospital
Weston, Florida, 33331
Fort Wayne Medical Oncology and Hematology, Inc.
Fort Wayne, Indiana, 46845
Physicians Clinic of Iowa
Cedar Rapids, Iowa, 52401-2112
Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Baptist Health Hardin
Elizabethtown, Kentucky, 42701
Frederick Health Hospital- James M Stockman Cancer Institute
Frederick, Maryland, 21704
Missouri Cancer Associates
Columbia, Missouri, 65201
SSM Health Cancer Care - St. Clare
Fenton, Missouri, 63026
Mary Lanning Healthcare (MLH) - Morrison Cancer Center (MCC)
Hastings, Nebraska, 68901-4470
Astera Cancer Care
East Brunswick, New Jersey, 08816
Summit Medical Group PA
Florham Park, New Jersey, 07932
The Valley Hospital - Valley Health System - The Robert and Audrey Luckow Pavilion
Paramus, New Jersey, 07652
Suny-Stony Brook University Cancer Center
Stony Brook, New York, 11794-9446
White Plains Hospital
White Plains, New York, 10601
Fletcher Hospital, Inc. dba AdventHealth Hendersonville
Hendersonville, North Carolina, 28792
Gabrail Cancer Center Research
Canton, Ohio, 44718
The Christ Hospital Cancer Center
Cincinnati, Ohio, 45219
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
The Cleveland Clinic Cancer Center At Fairview Hospital, Moll Pavilion
Cleveland, Ohio, 44111
Cleveland Clinic
Cleveland, Ohio, 44195-0001
Kettering Medical Center
Kettering, Ohio, 45429
Cleveland Clinic - Hillcrest Hospital
Mayfield Heights, Ohio, 44124
INTEGRIS Cancer Institute of Oklahoma
Oklahoma City, Oklahoma, 73109
University of Tennessee Medical Center
Knoxville, Tennessee, 37920
Baptist Cancer Center
Memphis, Tennessee, 38120
Millennium Research and Clinical Development, LLC
Houston, Texas, 77090
Virginia Cancer Specialists
Fairfax, Virginia, 22031
VCU Massey Cancer Center
Richmond, Virginia, 23298
Shenandoah Oncology
Winchester, Virginia, 22601