Safety and efficacy of BNT327, an investigational therapy, in combination with chemotherapy for patients with untreated small-cell 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

4 Feb 2026 → ongoing

Decision date (initial)

2025-12-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515765-34-00

ClinicalTrials.gov

NCT06712355

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the efficacy of BNT327 in combination with chemotherapy (etoposide plus carboplatin) followed by any subsequent therapy compared to atezolizumab in combination with chemotherapy (etoposide plus carboplatin) followed by any subsequent therapy in terms of a hazard ratio for overall survival (OS) in the intent-to-treat set (ITT Set).

Secondary objectives 5

1. To evaluate the progression-free survival (PFS) of BNT327 in combination with chemotherapy (etoposide plus carboplatin) compared to atezolizumab in combination with chemotherapy (etoposide plus carboplatin) in the ITT Set as measured by PFS according to RECIST v1.1 assessed by investigator.
2. To evaluate the antitumor activity of BNT327 in combination with chemotherapy (etoposide plus carboplatin) compared to atezolizumab in combination with chemotherapy (etoposide plus carboplatin) in the ITT Set as measured by objective response rate (ORR) and duration of response (DOR).
3. To evaluate the progression-free survival (PFS) rate and overall survival (OS) rate at fixed timepoints in each treatment arm for the ITT Set.
4. To evaluate the safety and tolerability of BNT327 in combination with chemotherapy (etoposide plus carboplatin) in the Safety Analysis Set.
5. To evaluate patient reported outcomes (PRO) scores of quality-of-life using the EORTC QLQ-C30, QLQ-LC29, and FACT-GP5 for the ITT Set.

Conditions and MedDRA coding

English First-line extensive-stage small-cell lung cancer (ES-SCLC)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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 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 are able to understand and follow trial-related instructions.
3. Are 18 years of age or older at the time of giving informed consent.
4. Have histologically or cytologically confirmed extensive-stage small-cell lung cancer (ES-SCLC).
5. Have not had prior systemic therapy for ES-SCLC.
6. Have at least one measurable lesion as the targeted lesion based on RECIST v1.1.
7. ECOG performance status of 0 or 1.
8. Have a body weight of at least 40 kg.
9. Have adequate hematologic (coagulation) and organ function (liver, kidney).
10. Are participants of child-bearing potential (POCBP) who have a negative serum beta-human chorionic gonadotropin test at screening within 7 days of the first investigational medicinal product (IMP) dose.
11. Are POCBP who agree to practice a highly effective form of contraception starting at the Screening Visit and continuously until 6 months after receiving the last dose of trial treatment or 7 months after the last dose of cisplatin, whichever is later, if cisplatin is received at any point during the induction period.
12. Men who are sexually active with a partner born female and have not had a vasectomy 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 Screening Visit and continuously until 6 months after receiving the last dose of trial treatment or 7 months after the last dose of cisplatin, whichever is later, if cisplatin is received at any point during the induction period.
13. 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 trial treatment or 7 months after the last dose of cisplatin, whichever is later, if cisplatin is received at any point during the induction period.

Exclusion criteria 25

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 active autoimmune disease or history of autoimmune diseases with anticipated relapse, except for clinically stable autoimmune thyroid disease or Type-1 diabetes, or skin disorders including psoriasis, vitiligo, or alopecia.
3. Have had other malignant tumors within 3 years prior to the trial treatment.
4. Have serious non-healing wounds or serious bone fractures.
5. Have significant risks of hemorrhage as defined in the study protocol.
6. Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
7. Have a history of serious Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior immunotherapy.
8. Have a known or suspected hypersensitivity to the trial treatments including any active ingredient or excipients thereof.
9. Have a known human immunodeficiency virus infection or known acquired immunodeficiency syndrome.
10. Participants with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen test result at screening).
11. Have an active hepatitis C virus infection.
12. Have any of the heart conditions within 6 months prior to the trial treatment as specified in the study protocol.
13. Have hypertension or diabetic conditions prior to trial treatment as specified in the study protocol.
14. Have 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.
15. Have histologically or cytologically confirmed small-cell lung cancer (SCLC) with combined histologies.
16. Have received any of the therapies or drugs within the time intervals prior to trial treatment as per study protocol.
17. Have undergone major organ surgery, have significant trauma, or invasive dental procedures within 21 days prior to the trial treatment or plan to undergo elective surgery during the trial.
18. Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
19. Have any of the central nervous system metastases as described in the study protocol.
20. Have adverse events (AEs) from prior antitumor therapy whose AE(s) have not returned to Grade 1 (graded by CTCAE 5.0 criteria) or below.
21. Have superior vena cava syndrome or symptoms of spinal cord compression that requires urgent medical intervention.
22. Have active, or a history of, pneumonitis requiring treatment with steroids, or has active, or a history of, interstitial lung disease.
23. Have active tuberculosis or have active syphilis infection.
24. Have an underlying condition that may increase the 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.
25. Are vulnerable individuals as per ICH E6 definition, i.e., are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS) defined as the time from randomization to death from any cause.

Secondary endpoints 13

1. Progression-free survival (PFS) defined as the time from randomization to first objective tumor progression, or death from any cause, whichever occurs first.
2. Objective response rate (ORR) defined as the proportion of participants in whom a complete response (CR) or partial response (PR) is observed as best overall response with confirmation.
3. Duration of response (DOR) defined as the time from onset of objective response (confirmed CR or PR based on investigator’s assessment) to first occurrence of objective tumor progression (progressive disease) or death from any cause, whichever occurs first.
4. Progression-free survival (PFS) rate based on investigator’s assessment at 6, 12, and 18 months.
5. Overall survival (OS) rate at 6, 12, 18, and 24 months.
6. Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs, by relationship.
7. Occurrence of dose delay, infusion interruption, and discontinuation of study treatment due to TEAEs (including related TEAEs)
8. Change from baseline in EORTC QLQ-C30 Global Health status / Quality-of-Life score (Items 29 and 30).
9. Change from baseline in EORTC QLQ-C30 physical functioning
10. Change from baseline in coughing scale of the EORTC quality-of-life-Lung cancer 29 questionnaire (QLQ-LC29).
11. Change from baseline in shortness of breath scale of the EORTC QLQ-LC29.
12. Change from baseline in "coughed up blood item" of the EORTC QLQ-LC29
13. Change from baseline in the Functional Assessment of Cancer Therapy overall bother item (FACT-GP5).

Investigational products

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

Test 1

Comparator 4

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 6

Locations

7 EU/EEA countries · 75 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 146 files

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

Application history

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