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

Phase 3RecruitingNCT06712316

BioNTech SE1,580 enrolled

Overview

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.

Each substudy contains a Phase 2 part followed by a Phase 3 part. In the Phase 2 part, participants will be randomized to one of two dose levels of pumitamig (also known as BNT327, BMS-986545, or PM8002) plus chemotherapy (Arm 1 and Arm 2). In the Phase 3 part, participants will be randomized to pumitamig plus chemotherapy (Arm 3) or pembrolizumab plus chemotherapy (Arm 4). In China, additional participants will be enrolled into the Phase 2 part of each substudy to receive pumitamig plus chemotherapy (Arm 1A) to further evaluate the selected Phase 3 dose. 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 and will confirm the progression of disease, if applicable. The planned study duration per study participant is up to 64 months.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,580

Conditions

Non-small Cell Lung Cancer

Interventions

PumitamigDRUG

Intravenous infusion

PembrolizumabDRUG

Intravenous infusion

CarboplatinDRUG

Intravenous infusion

Pemetrexed

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 as defined in the protocol. Key Exclusion Criteria: * Have histologically or cytologically confirmed NSCLC with small-cell lung cancer or neuroendocrine histologic 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 neoadjuvant/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). * Participants have superior vena cava syndrome or symptoms of spinal cord compression. NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Locations (365)

Outcomes

Primary Outcomes

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 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 Outcomes

Phase 3 - Overall survival (OS)

Central Contacts

BioNTech clinical trials patient information

CONTACT

+49 6131 9084 patients@biontech.de

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Intravenous infusion

PaclitaxelDRUG

Intravenous infusion

Birmingham Hematology and Oncology Associates LLC d/b/a Alabama Oncology

Birmingham, Alabama, United States

RECRUITING

Alaska Oncology and Hematology, LLC

Anchorage, Alaska, United States

RECRUITING

John Muir Clinical Research Center

Concord, California, United States

RECRUITING

University Of California - San Diego Moores Cancer Center

La Jolla, California, United States

RECRUITING

Vail Health

Vail, Colorado, United States

RECRUITING

MedStar Georgetown-MedStar Georgetown Transplant Institute University Hospital (MGUH)

Washington D.C., District of Columbia, United States

RECRUITING

MEDSTAR Washington Hospital Center (MedStar Health Research Institute)

Washington D.C., District of Columbia, United States

RECRUITING

Clermont Oncology Center

Clermont, Florida, United States

RECRUITING

SSAK Partners, LLC.

Coral Springs, Florida, United States

RECRUITING

Baptist Medical Center Jacksonville

Jacksonville, Florida, United States

RECRUITING

...and 355 more locations

For substudies A and B. OS defined as the time from randomization to death from any cause

Time frame: Up to approximately 5 years

Phase 2 - Duration of Response (DOR)

For substudies A and B. DOR defined as the time from first objective response (CR or PR per RECIST v1.1) to first occurrence of objective tumor progression (progressive disease per RECIST v1.1) or death from any cause, whichever occurs first.

Time frame: Up to approximately 2 years

Phase 2 - Disease Control Rate (DCR)

For substudies A and B. DCR defined as the proportion of participants in whom a confirmed CR or confirmed PR or stable disease (per RECIST v1.1, stable disease assessed at least 6 weeks after randomization) is observed as best overall response.

Time frame: Up to approximately 2 years

Phase 3 - PFS assessed by investigator

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

Phase 3 - ORR

For substudies A and B. ORR defined as the proportion of participants in whom a confirmed CR or confirmed PR (per RECIST v1.1) is observed as best overall response.

Time frame: Up to approximately 2 years

Phase 3 - PFS rate as assessed by BICR

For substudies A and B.

Time frame: At 6, 12, and 18 months

Phase 3 - PFS rate as assessed by investigator

For substudies A and B.

Time frame: At 6, 12, and 18 months

Phase 3 - OS rate

For substudies A and B.

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)

For substudies A and B. The EORTC QLQ-C30 is the most widely used cancer-specific, health related QoL instrument containing a total of 30 items and measures 5 functional scales (physical, role, emotional, cognitive, and social), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global health status/QoL scale. All the scales and single-item measures range in score from 0 to 100 with a high scale score representing a higher response level (i.e., high score for global health status/QoL is high QoL: high score for symptom scale/item is high symptomatology or problems).

Time frame: Up to approximately 5 years

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

For substudies A and B. The EORTC QLQ-C30 is the most widely used cancer-specific, health related QoL instrument containing a total of 30 items and measures 5 functional scales (physical, role, emotional, cognitive, and social), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global health status/QoL scale. All the scales and single-item measures range in score from 0 to 100 with a high scale score representing a higher response level (e.g., high score for functional scale is high/healthy level of 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)

For substudies A and B. The EORTC QLQ-LC29 is a disease-specific supplementary health-related quality-of-life (HRQoL) questionnaire module to be employed in conjunction with the QLQ-C30. It comprises 29 items and measures five multi-item scales (coughing, shortness of breath, side effects, tumor progression/existential issues, surgery-related symptoms) and five single items (coughing up blood, pain in chest, arm/shoulder and other parts of the body, and weight loss). All the scales and single-item measures range in score from 0 to 100 with a high score for the scales and single items representing a high level of symptomatology or problems.

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)

For substudies A and B. The NSCLC-SAQ is a 7-item patient-reported outcome (PRO) measure for use in adults to assess symptoms of advanced non-small cell lung cancer. It contains five domains and accompanying items that were identified as symptoms of non- small cell lung cancer: cough (1 item), pain (2), dyspnea (1), fatigue (2), and appetite (1). The (total) lowest score possible is 0, and the highest (total) score possible is 20. Higher scores indicate more severe symptoms.

Time frame: Up to approximately 5 years

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

For substudies A and B. The NSCLC-SAQ is a 7-item PRO measure for use in adults to assess symptoms of advanced non-small cell lung cancer. It contains five domains and accompanying items that were identified as symptoms of non-small cell lung cancer: cough (1 item), pain (2), dyspnea (1), fatigue (2), and appetite (1). The (total) lowest score possible is 0, and the highest (total) score possible is 20. Higher scores indicate more severe symptoms.

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)

For substudies A and B. The FACT-G - Item GP5 (Version 4) is a single-item summary measure of the overall impact of treatment toxicity, based upon its association with the number and degree of AEs in clinical studies. The single-item GP5 ("I am bothered by side effects of treatment") is rated on a 5-point Likert scale ("not at all" to "very much") with a recall period of past 7 days.

Time frame: Up to approximately 5 years

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

For substudies A and B. AEs graded according to CTCAE v5.0.

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)

For substudies A and B.

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