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

BioNTech

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: Pembrolizumab; Drug: Paclitaxel; Drug: Pumitamig; Drug: Carboplatin; Drug: Pemetrexed

Study type: Interventional

Funder types: Industry

Identifiers

NCT06712316

2024-515764-31-00 (EU Trial (CTIS) Number)

BNT327-06

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 1,580 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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1,580 participants in 10 patient groups

Substudy A Phase 2 (Arm 1) - Pumitamig Dose 1 + Carboplatin + Pemetrexed

Experimental group

Treatment:

Drug: Pemetrexed

Drug: Carboplatin

Drug: Pumitamig

Substudy A Phase 2 (Arm 2) - Pumitamig Dose 2 + Carboplatin + Pemetrexed

Experimental group

Treatment:

Drug: Pemetrexed

Drug: Carboplatin

Drug: Pumitamig

Substudy A Phase 2 (Arm 1A - China only) - Pumitamig Dose 3 + Carboplatin + Pemetrexed

Experimental group

Treatment:

Drug: Pemetrexed

Drug: Carboplatin

Drug: Pumitamig

Substudy A Phase 3 (Arm 3) - Pumitamig Dose 3 + Carboplatin + Pemetrexed

Experimental group

Treatment:

Drug: Pemetrexed

Drug: Carboplatin

Drug: Pumitamig

Substudy A Phase 3 (Arm 4) - Pembrolizumab + Carboplatin + Pemetrexed

Active Comparator group

Treatment:

Drug: Pemetrexed

Drug: Carboplatin

Drug: Pembrolizumab

Substudy B Phase 2 (Arm 1) - Pumitamig Dose 1 + Carboplatin + Paclitaxel

Experimental group

Treatment:

Drug: Carboplatin

Drug: Pumitamig

Drug: Paclitaxel

Substudy B Phase 2 (Arm 2) - Pumitamig Dose 2 + Carboplatin + Paclitaxel

Experimental group

Treatment:

Drug: Carboplatin

Drug: Pumitamig

Drug: Paclitaxel

Substudy B Phase 2 (Arm 1A, China only) - Pumitamig Dose 3 + Carboplatin + Paclitaxel

Experimental group

Treatment:

Drug: Carboplatin

Drug: Pumitamig

Drug: Paclitaxel

Substudy B Phase 3 (Arm 3) - Pumitamig Dose 3 + Carboplatin + Paclitaxel

Experimental group

Treatment:

Drug: Carboplatin

Drug: Pumitamig

Drug: Paclitaxel

Substudy B Phase 3 (Arm 4) - Pembrolizumab + Carboplatin + Paclitaxel

Active Comparator group

Treatment:

Drug: Carboplatin

Drug: Paclitaxel

Drug: Pembrolizumab