Evaluation of BNT327 Combined with Chemotherapy and Investigational Agents in First-Line Treatment of Non-Small Cell Lung Cancer
- Trial ID
- 2024-515764-31-00
- Protocol
- BNT327-06
- Sponsor
- BioNTech SE
Trial statistics
Objectives
The primary objective of this study is to evaluate the **safety** and **efficacy** of BNT327 in combination with chemotherapy in patients with non-small cell lung cancer. In the Phase II parts of sub-studies A and B, the focus is on assessing the safety and tolerability of BNT327 at two dose levels, as well as its efficacy when combined with chemotherapy. In the Phase III parts, the study aims to compare the efficacy of BNT327 in combination with chemotherapy to pembrolizumab plus chemotherapy, and to evaluate the efficacy of BNT327 followed by any subsequent therapy compared to pembrolizumab followed by any subsequent therapy. This is clinically relevant as it may offer insights into potential new treatment options for non-small cell lung cancer, potentially improving patient outcomes.
Secondary objectives include: - For the Phase II parts of sub-studies A and B: Evaluating the antitumor activity of BNT327 at two dose levels in combination with chemotherapy. - For the Phase III parts of sub-studies A and B: Evaluating the efficacy of BNT327 in combination with chemotherapy compared to pembrolizumab plus chemotherapy, assessing the safety and tolerability of BNT327 versus pembrolizumab, evaluating the antitumor activity of BNT327 compared to pembrolizumab, assessing progression-free survival (PFS) and overall survival (OS) rates at fixed timepoints, and evaluating patient-reported outcome (PRO) scores of quality-of-life questionnaires.
Participants
The clinical trial involves a total of **693 participants** diagnosed with **non-small cell lung cancer** (NSCLC). The study population includes both male and female subjects aged 18 years and older, with a confirmed diagnosis of Stage IIIB, IIIC, or Stage IV NSCLC, excluding those with actionable epidermal growth-factor receptor (EGFR) mutations or anaplastic lymphoma kinase rearrangements. Participants are required to have at least one measurable lesion based on RECIST v1.1 criteria and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial population was selected based on their ability to provide informed consent and comply with trial requirements, including lifestyle considerations such as the use of effective contraception methods and adherence to scheduled visits and treatment plans. Participants must have a minimum life expectancy of more than three months and adequate organ function. The trial includes a vulnerable population, ensuring comprehensive safety and efficacy evaluations of the investigational medicinal product, BNT327, in combination with chemotherapy.
Plans and Procedures
The clinical trial is a Phase II/III, multisite, randomized, double-blind, controlled study designed to evaluate the safety, tolerability, and efficacy of **BNT327** in combination with chemotherapy and other investigational agents in patients with non-small cell lung cancer (NSCLC). The trial is structured to include both Phase II and Phase III components, with the primary objective of assessing the safety and efficacy of BNT327 at two dose levels in combination with chemotherapy. The trial will compare the efficacy of BNT327 in combination with chemotherapy to **pembrolizumab** plus chemotherapy, with subsequent therapy options evaluated in the Phase III part.
The trial is expected to commence recruitment on April 1, 2025, and is estimated to conclude by March 30, 2029. Participants will be involved in the study for a maximum treatment period of 24 months, depending on the specific sub-study and treatment regimen. The trial will include several key study visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to assess overall outcomes. Participants will be required to attend scheduled visits, adhere to the treatment schedule, and comply with trial assessments and lifestyle restrictions.
Inclusion criteria for the trial require participants to be adults aged 18 years or older with a confirmed diagnosis of Stage IIIB, IIIC, or IV NSCLC without actionable EGFR mutations or anaplastic lymphoma kinase rearrangements. Participants must have at least one measurable lesion and an ECOG performance status of 0 or 1. Exclusion criteria are not explicitly detailed in the provided data. Conditions that may lead to early termination from the study include the occurrence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), or any other safety concerns as determined by the investigator.
The primary endpoints for the Phase II part include the occurrence of TEAEs, dose interruptions, and objective response rate (ORR). For the Phase III part, primary endpoints include progression-free survival (PFS) and overall survival (OS). Secondary endpoints will assess additional efficacy measures, quality of life, and safety outcomes. The trial will utilize a blinded independent central review to assess tumor progression and response, ensuring objective evaluation of treatment efficacy.
Treatment
The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and administration routes. **Paclitaxel Kabi** is provided as a 6 mg/mL concentrate for solution for infusion. It is administered as a **solution for intravenous infusion** with a maximum daily dose of 200 mg/m² and a total dose not exceeding 800 mg/m² over a treatment period of up to 12 weeks. The active substance, **paclitaxel**, is of chemical origin.
**KEYTRUDA**, containing the active substance **pembrolizumab**, is a 25 mg/mL concentrate for solution for infusion. It is administered as a solution for intravenous infusion with a maximum daily dose of 200 mg and a total dose of up to 3200 mg over a 24-week period. Pembrolizumab is a protein-based substance.
**Pemetrexed Fresenius Kabi** is a 25 mg/mL concentrate for solution for infusion, administered as a solution for infusion. The maximum daily dose is 500 mg/m², with a total dose limit of 16000 mg/m² over a 24-week treatment period. The active substance, **pemetrexed**, is of chemical origin.
**BNT327** is provided as a powder for concentrate for solution for infusion. It is administered as a solution for intravenous infusion with a maximum daily dose of 2000 mg and a total dose of up to 32000 mg over a 24-week period. The active substance, **BNT327**, is a protein-based substance.
**Carboplatin Kabi** is a 10 mg/mL concentrate for solution for infusion, administered as a solution for infusion. The maximum daily dose is 900 mg, with a total dose limit of 3600 mg over a 12-week treatment period. The active substance, **carboplatin**, is of chemical origin.
Throughout the trial, participant compliance with dosing schedules is monitored to ensure adherence to the prescribed treatment regimens. No non-experimental treatments, such as standard-of-care therapy or placebo, are specified in the trial protocol. The trial aims to evaluate the safety, tolerability, and efficacy of these investigational agents in combination with chemotherapy for the treatment of first-line non-small cell lung cancer.
Efficacy
The efficacy of the investigational agent **BNT327** in combination with chemotherapy will be assessed in a Phase II/III clinical trial involving patients with non-small cell lung cancer (NSCLC). The primary endpoints for the Phase II sub-studies include the objective response rate (ORR), defined as the proportion of participants achieving a confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 criteria. Additionally, the best percentage change from baseline in tumor size will be evaluated. For the Phase III sub-studies, the primary endpoints include progression-free survival (PFS), defined as the time from randomization to the first documented tumor progression or death from any cause, and overall survival (OS), defined as the time from randomization to death from any cause.
Secondary endpoints for the Phase II sub-studies include the duration of response (DOR), disease control rate (DCR), and the occurrence of treatment-emergent adverse events (TEAEs). For the Phase III sub-studies, secondary endpoints include PFS and OS rates at specified time intervals, changes from baseline in quality-of-life measures using the EORTC QLQ-C30 and QLQ-LC29 scales, and the occurrence of TEAEs. Efficacy assessments will be conducted using validated scales and criteria, such as RECIST v1.1, and will involve both investigator assessments and blinded independent central review (BICR) for certain endpoints. The schedule for measuring these parameters will be aligned with the trial's protocol, ensuring systematic data collection and analysis throughout the study duration.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Are able to give informed consent and have given written consent in accordance with ICH GCP and local legislation prior to the start of any trial-specific procedures.
- Are a POCBP who agree to practice a highly effective form of contraception and require their male sexual partners to use barrier contraception methods (preferably condoms) starting at the Screening Visit and continuously until 6 months after receiving the last dose of investigational medicinal product (IMP).
- Are men who are sterile or if they are potentially fertile and sexually active with a partner of childbearing potential, who agree to use condoms and to ask their sexual partners to practice a highly effective form of contraception during the trial, starting at the time of giving informed consent and continuously until 6 months after receiving the last dose of IMP.
- Agree not to donate and/or cryopreserve germ cells (sperm, oocytes, ova) for the purposes of assisted reproduction during trial, starting at screening and continuously until 6 months after the last dose of IMP.
- Are willing and able to comply with scheduled visits, treatment schedule, the planned trial assessments, laboratory tests, lifestyle restrictions, and other requirements of the trial. This includes that they can understand and follow trial-related instructions. Participants must provide a tumor tissue specimen and a documented PD-L1 status prior to randomization.
- Male or female, aged ≥18 years at the time of giving informed consent.
- Have systemic treatment naïve, 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 UICC/AJCC staging system, 8th edition . • Participants with non-squamous NSCLC will be enrolled to Substudy A. − Participants must be tested for EGFR mutations and ALK rearrangements; those with actionable results should not be enrolled. − If locally approved targeted first-line therapies are available, participants with known actionable mutations (other than EGFR and ALK alterations) should not be enrolled. Note: Testing for other genomic mutations is not mandated if not done as part of standard local practice. • Participants with squamous NSCLC will be enrolled to Substudy B. Mixed tumors which involve squamous tumor cells will be categorized as squamous cell NSCLC; if small cell elements are present, the participant is ineligible. − If the participant is <50 years old or has never smoked or quit smoking >15 years ago then they should be tested for EGFR mutations and ALK rearrangements; those with actionable results should not be enrolled.
- Have at least one measurable lesion as the targeted lesion based on RECIST v1.1.
- Have ECOG performance status of 0 or 1.
- Have adequate organ function regarding hematology, liver, renal, and coagulation.
- Are a person of child-bearing potential (POCBP) who have a negative serum beta-human chorionic gonadotropin test at screening and before each IMP dose.
Exclusion Criteria
- Are pregnant or breastfeeding or are planning pregnancy or to father children during the trial or within 6 months after the last dose of IMP.
- Have any of the following heart conditions within 6 months prior to the trial treatment: • Acute coronary syndrome, coronary artery bypass grafting, congestive heart failure, aortic dissection, stroke, arterial thrombosis, or other Grade 3 and above cardiovascular and cerebrovascular events. • New York Heart Association functional classification ≥II heart failure or left ventricular ejection fraction less than 50%. • Those who have ventricular arrhythmias requiring clinical intervention, second- to third-degree atrioventricular block, or congenital long QT syndrome. • Mean QT interval corrected by QTcF more than 480 ms.
- Have any of the following hypertension or diabetic conditions prior to trial treatment: • Uncontrolled hypertension (systolic blood pressure (BP) ≥160 mmHg and/or diastolic BP ≥100 mmHg) while on antihypertensive medicine within 7 days prior to the first dose of trial treatment. • Those with a history of hypertensive crisis or hypertensive encephalopathy. • Poorly controlled diabetes (fasting blood glucose ≥13.3 mmol/L [240 mg/dL] or HbA1C ≥8.5% [69 mmol/mol]) within 7 days prior to the first dose of trial treatment.
- Having a medical, psychological, or social condition which, in the opinion of the investigator, could compromise their wellbeing if they participate in the trial, or that could prevent, limit, or confound the protocol-specified assessments or procedures, or that could impact adherence to protocol-described requirements.
- 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 trial treatment: • Previous chemotherapy (platinum-based) or PD(L)-1 for treating NSCLC in either neoadjuvant/adjuvant or locally advanced/metastatic setting. • Receipt of an investigational drug or device within 30 days of screening or within five half-lives of the investigational drug (whichever is shorter). • 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 within 7 days prior to the initiation of trial treatment. • Have been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of the trial treatment. • Received broad-spectrum intravenous antibiotics therapy within 2 weeks prior to initiation of trial treatment.
- Have undergone major organ surgery, significant trauma, or invasive dental procedures within 21 days prior to the trial treatment or plan to undergo elective surgery during the trial.
- Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
- Have the following central nervous system metastases: • Participants with untreated brain metastases that are symptomatic. • Participants with treated central nervous system metastases who are not neurologically stable or on steroids (prednisone equivalent more than 10 mg/day) within 7 days before initiating trial treatment. • Participants with known metastases in spinal cord, or leptomeningeal carcinomatosis.
- Have active autoimmune disease or history of autoimmune diseases with anticipated relapse (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.) are not allowed, except for those with clinically stable autoimmune diseases such as autoimmune thyroid disease or Type 1 diabetes, or skin disorders including psoriasis, vitiligo, or alopecia.
- Have had other malignant tumours within 3 years prior to the trial treatment are not allowed. Except for those who have been cured with local treatment
- Have a serious or non-healing wound or (incompletely healed) bone fracture.
- Participants with significant risk of hemorrhage, (per investigator clinical judgment) indicated by any of the following criteria: -Tumors with clear radiographic evidence of major blood vessel invasion -Tumor lesions with clear invasion of major airways (such as tracheal invasion) or vital organs (such as the heart, pericardium, and esophagus). -At least one major cavitation posing hemorrhage risk. -Clinically significant hemoptysis -Intracranial or intraspinal hemorrhage within 3 months before randomization. -Gastrointestinal bleeding within 3 months before the first dose of trial treatment. -Vascular diseases (such as aortic aneurysm) with a risk of rupture within 3 months prior to randomization. -Therapeutic anticoagulation or antiplatelet therapy within 10 days before randomization. However, prophylactic use of anticoagulants is allowed.
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
- Participants with a history of serious Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior immunotherapy.
- Have a known or suspected hypersensitivity to the trial treatments including any active ingredient or excipients thereof.
- Have known human immunodeficiency virus infection or known acquired immunodeficiency syndrome, with the following exceptions: • Participants with CD4+ T-cell counts ≥350 cells/mL per local laboratory should generally be eligible for the trial. • Participants who have not had an opportunistic infection within the past 12 months.
- Participants with past hepatitis B virus infection or resolved hepatitis B virus infection.
- Have an active hepatitis C virus infection; individuals who have completed curative antiviral treatment with hepatitis C virus viral load below the limit of quantification are allowed.
- Participants with an adverse event (AE) from prior antitumor therapy whose AE(s) have not returned to Grade 1 or below are not eligible for the trial.
- Have superior vena cava syndrome or symptoms of spinal cord compression.
- Those with active, or a history of, pneumonitis requiring treatment with steroids, or has active, or a history of, interstitial lung disease. Those with a history of pulmonary fibrosis, or currently diagnosed with severe lung diseases such as interstitial pneumonia, pneumoconiosis, chemical pneumonitis, or any other condition resulting in significant impairment in lung function.
- Those with active tuberculosis or have active syphilis infection.
- Have an underlying condition that may increase risk of the combination treatment or complicate the interpretation of AEs, as judged by the investigator, or other scenarios that the investigators consider the participant is not eligible for the trial.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 26 Jan 2026 | 21 |
 Bulgaria | Recruiting | 26 Jan 2026 | 35 |
 France | Recruiting | 26 Jan 2026 | 35 |
 Germany | Recruiting | 26 Jan 2026 | 150 |
 Hungary | Recruiting | 26 Jan 2026 | 35 |
 Italy | Recruiting | 26 Jan 2026 | 61 |
 Poland | Recruiting | 26 Jan 2026 | 220 |
 Romania | Recruiting | 26 Jan 2026 | 40 |
 Spain | Recruiting | 26 Jan 2026 | 114 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PACLITAXEL | Test | PHF00230MIG | SOLUTION FOR INTRAVENOUS INFUSION | 200 | 12 | SCP129816 |
BNT327 | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | SOLUTION FOR INTRAVENOUS INFUSION | 2000 | 24 | PRD12821958 |
BNT327 | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | SOLUTION FOR INTRAVENOUS INFUSION | 2000 | 24 | PRD11607432 |
PEMBROLIZUMAB | Comparator | PHF00230MIG | SOLUTION FOR INTRAVENOUS INFUSION | 200 | 24 | SCP6094344 |
PEMETREXED | Test | PHF00230MIG | SOLUTION FOR INFUSION | 500 | 24 | SCP111841108 |
CARBOPLATIN | Test | PHF00230MIG | SOLUTION FOR INFUSION | 900 | 12 | SCP10337134 |