Overview Study details Eligibility Things to know Research Study plan

Simplify with AI

Overview Study details Eligibility Things to know Research Study plan

Simplify with AI

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

PHASE2PHASE3RECRUITING

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.

Study details:

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.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

Have 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, 8th edition without actionable epidermal growth factor receptor mutation or anaplastic lymphoma kinase (ALK) rearrangement.
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.

Exclusion criteria

Have histologically or cytologically confirmed NSCLC with small-cell lung cancer histologic component.
Have received any of the following therapies or drugs within the noted time intervals prior to study treatment: Participants who received prior treatment with anti-VEGF monoclonal antibody, or PD(L)-1/VEGF bispecific antibody or received platinum-based chemotherapy and/or anti-PD(L)-1 as part of adjuvant or neo-adjuvant treatment.
Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 14 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 non-healing wound, ulcer, or 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. 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 evidence of major coagulation disorders or other significant risks of hemorrhage.
Have superior vena cava syndrome or symptoms of spinal cord compression.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

Study type

TREATMENT

Phase

PHASE2PHASE3

Study ID

NCT06712316

Intervention or treatment

DRUG: Pumitamig

DRUG: Pembrolizumab

DRUG: Carboplatin

DRUG: Pemetrexed

DRUG: Paclitaxel

Conditions

Non-small Cell Lung Cancer

Condition: Non-small Cell Lung Cancer
DRUG: Pumitamig and other drugs
Adelaide, Australia and more
Sponsor: BioNTech SE

Save

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Cancer Research SA (CRSA)

Select from list below to view details:

Cancer Research SA (CRSA)
Adelaide, Australia
Royal Adelaide Hospital
Adelaide, Australia
Flinders Medical Centre
Bedford Park, Australia
Cairns Hospital
Cairns, Australia

Loading map...

Who is running the clinical trial?

BioNTech SE

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Substudy A Phase 2 (Arm 1) - Pumitamig Dose 1 + Carboplatin + Pemetrexed Not Specified	Drug: Pumitamig, Drug: Carboplatin, Drug: Pemetrexed
EXPERIMENTAL: Substudy A Phase 2 (Arm 2) - Pumitamig Dose 2 + Carboplatin + Pemetrexed Not Specified	Drug: Pumitamig, Drug: Carboplatin, Drug: Pemetrexed
EXPERIMENTAL: Substudy A Phase 2 (Arm 1A - China only) - Pumitamig Dose 3 + Carboplatin + Pemetrexed Not Specified	Drug: Pumitamig, Drug: Carboplatin, Drug: Pemetrexed
EXPERIMENTAL: Substudy A Phase 3 (Arm 3) - Pumitamig Dose 3 + Carboplatin + Pemetrexed Not Specified	Drug: Pumitamig, Drug: Carboplatin, Drug: Pemetrexed
ACTIVE_COMPARATOR: Substudy A Phase 3 (Arm 4) - Pembrolizumab + Carboplatin + Pemetrexed Not Specified	Drug: Pembrolizumab, Drug: Carboplatin, Drug: Pemetrexed
EXPERIMENTAL: Substudy B Phase 2 (Arm 1) - Pumitamig Dose 1 + Carboplatin + Paclitaxel Not Specified	Drug: Pumitamig, Drug: Carboplatin, Drug: Paclitaxel
EXPERIMENTAL: Substudy B Phase 2 (Arm 2) - Pumitamig Dose 2 + Carboplatin + Paclitaxel Not Specified	Drug: Pumitamig, Drug: Carboplatin, Drug: Paclitaxel
EXPERIMENTAL: Substudy B Phase 2 (Arm 1A, China only) - Pumitamig Dose 3 + Carboplatin + Paclitaxel Not Specified	Drug: Pumitamig, Drug: Carboplatin, Drug: Paclitaxel
EXPERIMENTAL: Substudy B Phase 3 (Arm 3) - Pumitamig Dose 3 + Carboplatin + Paclitaxel Not Specified	Drug: Pumitamig, Drug: Carboplatin, Drug: Paclitaxel
ACTIVE_COMPARATOR: Substudy B Phase 3 (Arm 4) - Pembrolizumab + Carboplatin + Paclitaxel Not Specified	Drug: Pembrolizumab, Drug: Carboplatin, Drug: Paclitaxel

What is the study measuring?

Primary Outcome

Measure	Description	Time Frame
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.	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.	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.	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.	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.	Up to approximately 5 years
Phase 3 - Overall survival (OS)	For substudies A and B. OS defined as the time from randomization to death from any cause	Up to approximately 5 years

Secondary Outcome

Measure	Description	Time Frame
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.	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.	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.	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.	Up to approximately 2 years
Phase 3 - PFS rate as assessed by BICR	For substudies A and B.	At 6, 12, and 18 months
Phase 3 - PFS rate as assessed by investigator	For substudies A and B.	At 6, 12, and 18 months
Phase 3 - OS rate	For substudies A and B.	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).	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 (i.e., high score for functional scale is high/healthy level of functioning).	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.	Up to approximately 5 years
Phase 3 - Change from baseline in shortness of breath scale of the EORTC 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.	Up to approximately 5 years
Phase 3 - Change from baseline in coughed up blood item of the EORTC 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.	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 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.	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.	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.	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.	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.	From the first dose of IMP to the 90-day Follow-Up Visit

Are you running this trial?If you're a clinic or sponsor, you can claim this study.

Claim this trial

References

Clinical Trials Gov: Safety, Effectiveness, and Pharmacokinetics of BNT327 in Combination With Chemotherapy and Other Investigational Agents for Lung Cancer

Other trials to consider

Loading suggested trials...