A clinical trial to test if an investigational combination therapy with BNT326 and BNT327 is safe and potentially beneficial for people with advanced non-small cell lung cancer (NSCLC)

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

16 Mar 2026 → ongoing

Decision date (initial)

2025-12-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

BioNTech SE

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

Part 1 – Dose Escalation: To determine the recommended phase 2 dose (RP2D) of BNT326 in combination with BNT327 by assessing the safety and tolerability in participants with advanced NSCLC. Part 2a – Dose Expansion: To assess the safety profile of BNT326 in combination with BNT327. To assess the efficacy of BNT326 in combination with BNT327. Part 2b – Dose Optimization: To assess the efficacy and determine the optimized dose of BNT326 in combination with BNT327.

Secondary objectives 5

1. Part 1 – Dose Escalation, Part 2a – Dose Expansion and Part 2b – Dose Optimization: To evaluate the efficacy of BNT326 in combination with BNT327.
2. Part 2b – Dose optimization: To assess the safety profile of BNT326 in combination with BNT327.
3. Part 2b – Dose optimization: To evaluate the efficacy (other than ORR) of BNT326 in combination with BNT327.
4. All Cohorts: To assess the pharmacokinetics (PK) of BNT326 in combination therapy with BNT327.
5. All Cohorts: To evaluate immunogenicity of BNT326 in combination therapy with BNT327.

Conditions and MedDRA coding

Non-small Cell Lung Cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Aged ≥18 years at the time of giving informed consent.
2. Have measurable disease defined by RECIST v1.1.
3. All participants have to provide a tumor tissue sample from archival tissue. Alternatively, a fresh biopsy should be collected, unless medically not justifiable to be conducted.
4. Have Eastern Cooperative Oncology Group performance status of 0 or 1.
5. Have adequate organ and bone marrow function within 7 days before randomization/enrollment.
6. All parts: Have advanced non-squamous or squamous NSCLC.

Exclusion criteria 15

1. Had disease progression on or were intolerant to prior treatment with an agent targeting HER3 or with a topoisomerase I inhibitor payload. Note: For Part 2a Cohort A, prior exposure to agents targeting HER3 or topoisomerase I inhibitor payload may be allowed on a case-by-case basis after discussion with and approval by the sponsor.
2. Have urine protein ≥2+ and 24-hour urine protein excretion ≥1 g. If qualitative urine protein is ≤1+, a 24-hour urine protein quantitative test is not required.
3. Have a history of Grade ≥3 immune-related adverse events that led to treatment discontinuation of a prior checkpoint inhibitor.
4. Have clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
5. Participants with significant risks of hemorrhage or evidence of major coagulation disorders.
6. Have active or chronic corneal disorders or with any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.
7. Have an uncontrolled concomitant or intercurrent illness, that contraindicates study participation, limits compliance with study procedures or substantially increases the risk of incurring adverse events (AEs).
8. Have left ventricular ejection fraction < 50 % by either echocardiography or multi-gated acquisition within 28 days before randomization/enrollment.
9. Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
10. Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
11. Have had exposure to protocol-specific treatments with a washout period before randomization/enrollment.
12. Are participants of childbearing potential who are pregnant or breastfeeding or are planning pregnancy within the time specified in the protocol or are potentially fertile males, who are planning to father children during the study or within the time specified in the protocol.
13. Are subject to exclusion periods from another investigational study.
14. Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
15. Cohort C: 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1: Are eligible for 2L therapy with amivantamab in combination with chemotherapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1 - Occurrence of dose limiting toxicities (DLTs) within a participant during the DLT evaluation period
2. Part 1 and Part 2a - Occurrence of treatment emergent adverse events (TEAEs), treatment-related adverse events (TRAE), treatment emergent serious adverse events (TESAE), treatment-related serious adverse events (TRSAE)
3. Part 1 and Part 2a - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs
4. Part 2a and Part 2b - Objective response rate (ORR): Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) is observed as best overall response.

Secondary endpoints 11

1. Part 1 – ORR: Defined as the percentage of participants in whom a confirmed CR or PR (per RECIST v1.1 based on the investigator’s assessment) is observed as best overall response.
2. Part 2b - Occurrence of TEAEs, TRAEs, TESAEs, TRSAEs
3. Part 2b - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs
4. Part 2a and Part 2b - Progression free survival based on the investigator's assessment: Defined as the time from first dose of IMP to the first objective tumor progression or death from any cause, whichever occurs first.
5. Part 2a and Part 2b - Disease control rate: Defined as the proportion of participants with CR, PR, or stable disease as best overall response.
6. Part 2a and Part 2b - Duration of response: Defined as the time from first confirmed objective response (CR or PR per RECIST v1.1 based on the investigator’s assessment) to first occurrence of objective tumor progression or death from any cause, whichever occurs first
7. Part 2a and Part 2b - Time to response: Defined as the time from first dose of IMP to first confirmed objective response in participants with a confirmed objective response
8. Part 2a and Part 2b - Overall survival: Defined as the time from first dose of IMP to death from any cause
9. All cohorts - PK assessment: Maximum concentration derived from serum concentrations of BNT326 ADC, total anti-HER3 antibody component, and unconjugated payload. For applicable participants, if data permits.
10. All cohorts - PK assessment: Time to reach maximum (peak) serum concentration derived from serum concentrations of BNT326 ADC, total anti-HER3 antibody component, and unconjugated payload. For applicable participants, if data permits.
11. All cohorts - Anti-drug antibody (ADA) prevalence and ADA incidence. By cohort and combination treatment regimen for applicable participants.

Investigational products

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

Test 6

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 10

Locations

4 EU/EEA countries · 33 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 62 files

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

Application history

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