Safety, Effectiveness, 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: Carboplatin; Drug: Paclitaxel; Drug: Pembrolizumab; Drug: BNT327; 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. Participants will be randomized to one of two dose levels of BNT327 plus chemotherapy for the Phase 2 part of each substudy. After the analysis of the Phase 2 data (efficacy, safety, and exposure-response), an internal review committee (IRC) will decide whether participants will be treated with BNT327 at dose level 1 or 2 in the Phase 3 part of the substudies. After dose selection, the selected dose will be used for all participants in the study. For the Phase 3 parts of both substudies, an independent data monitoring committee (IDMC) will be established as needed to provide independent review of the data during the study.

The sponsor may decide not to perform or stop recruiting participants in the Phase 2 part of the study depending on data generated in the BNT327-01 (NCT06449209) and BNT327-02 (NCT06449222) studies. The sponsor may also choose not to continue all substudies.

Enrollment: 982 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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 EGFR mutation or anaplastic lymphoma kinase 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 (ECOG) performance status of 0 or 1.
• Adequate organ function.

Key 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 neoadjuvant 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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982 participants in 8 patient groups

Substudy A Phase 2 - BNT327 Dose 1 + Carboplatin + Pemetrexed

Experimental group

Treatment:

Drug: Pemetrexed

Drug: BNT327

Drug: Carboplatin

Substudy A Phase 2 - BNT327 Dose 2 + Carboplatin + Pemetrexed

Experimental group

Treatment:

Drug: Pemetrexed

Drug: BNT327

Drug: Carboplatin

Substudy A Phase 3 - BNT327 + Carboplatin + Pemetrexed

Experimental group

Description:

BNT327 selected dose for Phase 3

Treatment:

Drug: Pemetrexed

Drug: BNT327

Drug: Carboplatin

Substudy A Phase 3 - Pembrolizumab + Carboplatin + Pemetrexed

Active Comparator group

Treatment:

Drug: Pemetrexed

Drug: Pembrolizumab

Drug: Carboplatin

Substudy B Phase 2 - BNT327 Dose 1 + Carboplatin + Paclitaxel

Experimental group

Treatment:

Drug: BNT327

Drug: Paclitaxel

Drug: Carboplatin

Substudy B Phase 2 - BNT327 Dose 2 + Carboplatin + Paclitaxel

Experimental group

Treatment:

Drug: BNT327

Drug: Paclitaxel

Drug: Carboplatin

Substudy B Phase 3 - BNT327 + Carboplatin + Paclitaxel

Experimental group

Description:

BNT327 selected dose for Phase 3

Treatment:

Drug: BNT327

Drug: Paclitaxel

Drug: Carboplatin

Substudy B Phase 3 - Pembrolizumab + Carboplatin + Paclitaxel

Active Comparator group

Treatment:

Drug: Pembrolizumab

Drug: Paclitaxel

Drug: Carboplatin