Safety, efficacy, and pharmacokinetics of BNT327 in combination with chemotherapy and other investigational agents for lung cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BioNTech SE

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Jun 2025 → ongoing

Decision date (initial)

2025-04-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515764-31-00

ClinicalTrials.gov

NCT06712316

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Dose response, Pharmacokinetic, Safety, Efficacy

For the Phase II parts of sub-studies A and B: To evaluate the safety and tolerability of BNT327 at two dose levels in combination with chemotherapy. To evaluate the efficacy of BNT327 at two dose levels in combination with chemotherapy.
For the Phase III parts of sub-studies A and B: To compare efficacy of BNT327 in combination with chemotherapy to pembrolizumab plus chemotherapy.

Secondary objectives 7

1. For the Phase II parts of sub-studies A and B: To evaluate the antitumor activity of BNT327 at two dose levels in combination with chemotherapy. For the Phase 3 part: To evaluate the efficacy of BNT327 in combination with chemotherapy compared to pembrolizumab plus chemotherapy.
2. For Phase III parts of sub-studies A and B: To evaluate the safety and tolerability of BNT327 in combination with chemotherapy a versus pembrolizumab plus chemotherapy.
3. For the Phase III parts of sub-studies A and B: To evaluate the antitumor activity of BNT327 in combination with chemotherapy compared to pembrolizumab plus chemotherapy.
4. For the Phase III parts of sub-studies A and B: To evaluate the progression-free survival (PFS) rate and overall survival (OS) rate at fixed timepoints in each treatment arm.
5. For the Phase III parts of sub-studies A and B: To evaluate patient-reported outcome (PRO) scores of quality-of-life questionnaires.
6. For the Phase III parts of sub-studies A and B: To evaluate the safety and tolerability of BNT327 in combination with chemotherapy a versus pembrolizumab plus chemotherapy.
7. For the Phase III parts of sub-studies A and B: To compare efficacy of BNT327 in combination with chemotherapy followed by any subsequent therapy to pembrolizumab plus chemotherapy followed by any subsequent therapy.

Conditions and MedDRA coding

Non-small cell lung cancer

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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.
2. 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).
3. 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.
4. 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.
5. 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.
6. Male or female, aged ≥18 years at the time of giving informed consent.
7. 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.
8. Have at least one measurable lesion as the targeted lesion based on RECIST v1.1.
9. Have ECOG performance status of 0 or 1.
10. Have adequate organ function regarding hematology, liver, renal, and coagulation.
11. 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 24

1. 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.
2. 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.
3. 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.
4. 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.
5. Have histologically or cytologically confirmed NSCLC with small cell lung cancer or neuroendocrine histologic component.
6. 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.
7. 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.
8. Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
9. 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.
10. 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.
11. 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
12. Have a serious or non-healing wound or (incompletely healed) bone fracture.
13. 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.
14. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
15. Participants with a history of serious Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior immunotherapy.
16. Have a known or suspected hypersensitivity to the trial treatments including any active ingredient or excipients thereof.
17. 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.
18. Participants with past hepatitis B virus infection or resolved hepatitis B virus infection.
19. 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.
20. 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.
21. Have superior vena cava syndrome or symptoms of spinal cord compression.
22. 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.
23. Those with active tuberculosis or have active syphilis infection.
24. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. For the Phase II parts of sub-studies A and B: Occurrence of treatment-emergent adverse events (TEAE) (including Grade ≥3), adverse events of special interest (AESIs), treatment-related TEAEs, treatment emergent serious adverse events (SAE), and treatment-related treatment-emergent SAEs in the combination treatment regimen from the first dose of investigational medicinal product (IMP) to the 90-day Follow-Up Visit.
2. For the Phase II parts of sub-studies A and B: Occurrence of dose interruptions, reductions, and discontinuations of IMP due to TEAEs (including related TEAEs) from the first dose of IMP to the 90-day Follow-Up Visit.
3. For the Phase II parts of sub-studies A and B: Objective response rate (ORR) defined as the proportion of participants in whom a confirmed complete response (CR) or confirmed partial response (PR) (per RECIST v1.1 based on the investigator’s assessment) is observed as best overall response.
4. For the Phase II parts of sub-studies A and B: Best percentage change from baseline in tumor size (based on investigator’s tumor assessment according to RECIST 1.1).
5. For the Phase III parts of sub-studies A and B: Progression-free survival (PFS) defined as the time from randomization to first documented tumour progression (progressive disease assessed by blinded independent central review (BICR) per RECIST v1.1), or death from any cause, whichever occurs first.

Secondary endpoints 18

1. For the Phase II parts of sub-studies A and B: Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST v1.1) to first occurrence of objective tumour progression (progressive disease per RECIST v1.1) or death from any cause, whichever occurs first.
2. For the Phase II parts of sub-studies A and B: Disease control rate (DCR) defined as the proportion of participants in whom a confirmed CR or confirmed PR or stable disease (per RECIST v1.1, stable disease assessed at least 6 weeks after randomization) is observed as best overall response.
3. For the Phase III parts of sub-studies A and B: Progression-free survival (PFS) defined as the time from randomization to first documented tumour progression (progressive disease assessed by investigator per RECIST v1.1), or death from any cause, whichever occurs first.
4. For the Phase III parts of sub-studies A and B: Objective response rate (ORR) defined as the proportion of participants in whom a confirmed CR or confirmed PR (per RECIST v1.1) is observed as best overall response.
5. For the Phase III parts of sub-studies A and B: Progression-free survival (PFS) rate as assessed by blinded independent central review (BICR) at 6, 12, and 18 months.
6. For the Phase III parts of sub-studies A and B: PFS rate as assessed by investigator at 6, 12, and 18 months.
7. For the Phase III parts of sub-studies A and B: Overall survival (OS) rate at 6, 12, 18, and 24 months.
8. For the Phase III parts of sub-studies A and B: Change from baseline in EORTC QLQ-C30 Global Health status/Quality-of-Life score (Items 29 and 30).
9. For the Phase III parts of sub-studies A and B: Change from baseline in EORTC QLQ-C30 physical functioning.
10. For the Phase III parts of sub-studies A and B: Change from baseline in the “coughing” scale of the EORTC QLQ-LC29.
11. For the Phase III parts of sub-studies A and B: Change from baseline in the “shortness of breath” scale of the EORTC QLQ-LC29.
12. For the Phase III parts of sub-studies A and B: Change from baseline in the “coughed-up blood” item of the EORTC QLQ-LC29.
13. For the Phase III parts of sub-studies A and B: Change from baseline in the “fatigue domain” score scale of the NSCLC-SAQ.
14. For the Phase III parts of sub-studies A and B: Change from baseline in the “pain domain” score of the NSCLC-SAQ.
15. For the Phase III parts of sub-studies A and B: Change from baseline in FACT-G overall bother item (FACT-GP5).
16. For the Phase III parts of sub-studies A and B: Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs by relationship, according to CTCAE v5.0.
17. For the Phase III parts of sub-studies A and B: Occurrence of dose interruptions, reductions, and discontinuations of IMP due to TEAEs (including related TEAEs) from the first dose of IMP to the 90-day Follow-Up Visit.
18. For the Phase III parts of sub-studies A and B: Overall survival (OS) defined as the time from randomization to death from any cause.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BioNTech SE

Sponsor organisation

BioNTech SE

Address

An Der Goldgrube 12, Oberstadt Oberstadt

City

Mainz

Postcode

55131

Country

Germany

Scientific contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

BioNTech SE

Contact name

Clinical Trial Information Desk

Third parties 7

Locations

9 EU/EEA countries · 151 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 168 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications