Clinical trial NCT06841055: Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Non-small Cell Lung Cancer in Combination With Chemotherapy Following Chemoimmunotherapy
Official title: A Phase II, Multisite, Open-label, Single Arm Trial of BNT327 in Combination With Docetaxel in Second-line Stage IV Non-small Cell Lung Cancer (NSCLC) Following Chemoimmunotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Second-line treatment
Immunotherapy
Combination with other investigational agents
Bispecific antibody
Vascular endothelial growth factor (VEGF) A
Programmed death-ligand 1 (PD-L1)
Combination with chemotherapy
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
First posted: 2025-02-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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 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 BNT327 plus docetaxel.

Detailed 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 BNT327 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.

Eligibility 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.

Primary outcomes:
measure: Part 1 - Occurrence of DLTs
timeFrame: up to 21 days after first dose of investigational medicinal product (IMP)
measure: Part 1 and Part 2 - Occurrence of BNT327 treatment emergent adverse events (TEAEs), treatment-related TEAEs, treatment emergent serious adverse events (TESAEs), treatment-related (TRSAEs), and adverse events of special interest (AESIs)
timeFrame: from initiation of the first dose of IMP to the 90-day Follow-Up visit
measure: Part 1 and Part 2 - Occurrence of dose interruption, dose reduction, and/or participant discontinuation due to adverse events (AEs)
timeFrame: from initiation of the first dose of IMP until the 90-day Safety Follow-up visit
measure: Part 1 and Part 2 - Objective response rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Part 1 and Part 2 - Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Part 1 and Part 2- Progression-free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Part 1 and Part 2 - Depth of Response
timeFrame: Up to approximately 2 years
measure: Part 1 and Part 2 - Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Part 1 and Part 2 - Time to Response (TTR)
timeFrame: Up to approximately 2 years
measure: Part 1 and Part 2 - Overall Survival (OS)
timeFrame: Up to approximately 2 years
measure: Part 1 and Part 2 - PK assessment: Maximum concentration (Cmax) derived from serum concentration of BNT327
timeFrame: from pre-dose to the end of study treatment (up to approximately 2 years)
measure: Part 1 and Part 2 - Number of participants developing detectable anti-BNT327 antibodies in serum
timeFrame: from pre-dose to the end of study treatment (up to approximately 2 years)
Other outcomes:
Locations:
city: Houston
country: United States
facility: Millennium Research and Clinical Development, LLC
state: Texas
Study officials:
affiliation: BioNTech SE
name: BioNTech Responsible Person
role: STUDY_DIRECTOR
References: