Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Non-small Cell Lung Cancer in Combination With Chemotherapy Following Chemoimmunotherapy
- Registration Number
- NCT06841055
- Lead Sponsor
- BioNTech SE
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
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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.
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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.
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Eastern cooperative oncology group performance status of 0 or 1.
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Adequate organ function.
Key
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1A - BNT327 Dose 1 + docetaxel BNT327 - Part 1A - BNT327 Dose 1 + docetaxel Docetaxel - Part 1B - BNT327 Dose 2 + docetaxel BNT327 - Part 1B - BNT327 Dose 2 + docetaxel Docetaxel - Part 2 - Selected doses of BNT327 + docetaxel BNT327 Dose expansion at the deemed safe dose Part 2 - Selected doses of BNT327 + docetaxel Docetaxel Dose expansion at the deemed safe dose
- Primary Outcome Measures
Name Time Method Part 1 - Occurrence of DLTs up to 21 days after first dose of investigational medicinal product (IMP) During the DLT evaluation period by dose level
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) from initiation of the first dose of IMP to the 90-day Follow-Up visit Graded according to the (US) National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Part 1 and Part 2 - Occurrence of dose interruption, dose reduction, and/or participant discontinuation due to adverse events (AEs) from initiation of the first dose of IMP until the 90-day Safety Follow-up visit Part 1 and Part 2 - Objective response rate (ORR) Up to approximately 2 years Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) based on investigator's review) is observed as best overall response
- Secondary Outcome Measures
Name Time Method Part 1 and Part 2 - Duration of Response (DOR) Up to approximately 2 years Defined as the time from first objective response (CR or PR per RECIST v1.1 based on the investigator's assessment) to first occurrence of objective tumor progression (progressive disease, per RECIST v1.1 based on the investigator's assessment) or death from any cause, whichever occurs first
Part 1 and Part 2- Progression-free Survival (PFS) Up to approximately 2 years Based on the investigator's assessment defined as the time from first dose of IMP to the first objective tumor progression (progressive disease per RECIST v1.1) or death from any cause, whichever occurs first
Part 1 and Part 2 - Depth of Response Up to approximately 2 years Defined as the maximum percent reduction from baseline in tumor size measured by sum of target lesion diameter (including nodal \[short axis\] and non-nodal \[longest axis\] lesions)
Part 1 and Part 2 - Disease Control Rate (DCR) Up to approximately 2 years Defined as the proportion of participants with confirmed CR, confirmed PR, or stable disease (per RECIST v1.1 based on the investigator's assessment) as best overall response
Part 1 and Part 2 - Time to Response (TTR) Up to approximately 2 years Defined as the time from first dose of IMP to first objective response (CR or PR per RECIST v1.1 based on the investigator's assessment)
Part 1 and Part 2 - Overall Survival (OS) Up to approximately 2 years Defined as the time from first dose of IMP to death from any cause
Part 1 and Part 2 - PK assessment: Maximum concentration (Cmax) derived from serum concentration of BNT327 from pre-dose to the end of study treatment (up to approximately 2 years) Part 1 and Part 2 - Number of participants developing detectable anti-BNT327 antibodies in serum from pre-dose to the end of study treatment (up to approximately 2 years)
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Trial Locations
- Locations (1)
Millennium Research and Clinical Development, LLC
🇺🇸Houston, Texas, United States