Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Non-small Cell Lung Cancer in Combination With Chemotherapy Following Chemoimmunotherapy

BioNTech

Status and phase: Enrolling; Phase 2

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: Docetaxel; Drug: Pumitamig

Study type: Interventional

Funder types: Industry

Identifiers

NCT06841055

2024-518279-80-00 (EU Trial (CTIS) Number)

BNT327-07

Details and patient eligibility

About

This is a Phase II, multisite, open-label, single arm study with two parts in participants with advanced/metastatic NSCLC which progressed after a first-line chemoimmunotherapy.

Part 1 is safety run-in with pumitamig (BNT327) (Dose 1 or Dose 2) plus docetaxel and will include up to 12 participants to be treated in Part 1A and 1B sequentially.

Part 2 is a dose expansion at the deemed safe dose of pumitamig plus docetaxel.

Full description

If the dose level (either from Part 1A or 1B) seems tolerable, an internal review committee will decide if the study can proceed to Part 2 and enroll additional participants.

Study participants will receive pumitamig in combination with docetaxel until disease progression, the occurrence of intolerable toxicity, study participant withdrawal, death, study termination or 2-year limit (whichever comes first).

After completion of study treatment, except for participants who withdraw informed consent, a long-term follow-up will be conducted for all participants to record disease progression, subsequent new anticancer treatments, and survival status.

Enrollment: 60 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 IV NSCLC that has documented radiographic progression on one or after one prior line of systemic treatment (programmed death-1 [PD-1]/ programmed death ligand-1 [PD-L1] inhibitor and platinum-based chemotherapy concomitantly) in advanced/metastatic setting per the American Joint Committee on Cancer staging system, 8th edition.

  • Participants must have received minimum two cycles of immunotherapy in first-line treatment to be eligible to this trial.
  • Only one prior line of immunotherapy containing regimen is allowed in advanced/metastatic setting. If participant had received adjuvant immunotherapy the disease-free interval (after the last dose of adjuvant immunotherapy) should be at least 6 months.
  • Historical PD-L1 results must be available.
  • Patients with actionable genetic alterations are allowed to be enrolled if patients received locally approved and available targeted agent in combination with immunotherapy in first-line advanced/metastatic setting.
  • Enrollment of participants with primary resistance (best response being radiological progression to prior immunochemotherapy) will be capped under 30% in the overall trial population.

• Have at least one measurable lesion as the targeted lesion based on RECIST v1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been documented after irradiation. Historical images within 28 days of the Screening Visit may be accepted as a screening image if deemed acceptable in the opinion of the investigator.

• Eastern cooperative oncology group performance status of 0 or 1.

• Adequate organ function.

Key Exclusion Criteria:

• Known hypersensitivity to the study treatments, their metabolites or formulation of excipients including polysorbate 80 (see Docetaxel label).
• Participants who received prior treatment with anti-vascular endothelial growth factor (VEGF) monoclonal antibody, or anti-PD-(L)-1/aVEGF bispecific antibody or docetaxel as monotherapy or in combination with other agents.
• Have received more than one prior lines of therapies in advanced/metastatic setting.
• 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 (except for docetaxel premedication). 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 or esophageal and gastric varices, or acute gastrointestinal bleeding. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the 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: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

60 participants in 3 patient groups

Part 1A - Pumitamig Dose 1 + docetaxel

Experimental group

Treatment:

Drug: Pumitamig

Drug: Docetaxel

Part 1B - Pumitamig Dose 2 + docetaxel

Experimental group

Treatment:

Drug: Pumitamig

Drug: Docetaxel

Part 2 - Selected doses of pumitamig + docetaxel

Experimental group

Description:

Dose expansion at the deemed safe dose

Treatment:

Drug: Pumitamig

Drug: Docetaxel