A clinical study to investigate the efficacy and safety of an investigational combination therapy with BNT324 and BNT327 in patients with advanced 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

20 Apr 2026 → ongoing

Decision date (initial)

2026-02-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-520238-31-01

ClinicalTrials.gov

NCT06892548

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

Part 1 (Dose Escalation): To determine the recommended phase II dose (RP2D) of BNT324 in combination with BNT327 by assessing the safety and tolerability in participants with advanced lung cancer. Part 2 (Dose Optimization/Signal Seeking): Lead indications Cohort 1 and Cohort 2: To determine the optimal dose of BNT324 in combination with BNT327 by assessing the safety profile and efficacy of the combination therapy in the randomized dose optimization cohorts in the lead cohorts (Cohort 1 treatment naive non-sq non-small cell lung cancer (NSCLC) and Cohort 2 relapsed/progressive small cell lung cancer (SCLC)). Efficacy signal seeking cohorts 3-7: To evaluate the efficacy of BNT324 in combination with BNT327 according to response evaluation criteria in solid tumors (RECIST) v1.1.

Secondary objectives 3

1. Part 1 (Dose Escalation): To evaluate the efficacy of BNT324 in combination with BNT327 according to RECIST v1.1.
2. Part 2 (Dose Optimization/Signal Seeking): To evaluate the efficacy (other than objective response rate (ORR)) of BNT324 in combination with BNT327 in dose optimization/signal seeking cohorts 1-7.
3. Part 2 (Dose Optimization/Signal Seeking): To assess the safety of BNT324 in combination with BNT327 in the signal seeking cohorts 3-7.

Conditions and MedDRA coding

Advanced Lung Cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Aged ≥18 years at the time of giving informed consent.
2. Histological or cytological confirmed unresectable advanced/metastatic lung cancer. Histological classification may be based on tumor samples prior to metastatic disease. Participants with mixed histology must be classified based on the main component. Participants with NSCLC are eligible with any or no PD-L1 expression. Participants with AGA-positive disease must have received targeted therapy prior to enrollment in this study.
3. Have measurable disease defined by RECIST version 1.1.
4. Have an Eastern Cooperative Oncology Group performance status of 0 or 1.
5. Have a life expectancy of ≥12 weeks.

Exclusion criteria 4

1. Prior treatment with B7-H3 targeted therapy.
2. Prior treatment with ADC with topoisomerase inhibitor (e.g., datopotamab deruxtecan, trastuzumab deruxtecan). Note: This exclusion applies to participants in the first-line/treatment-naïve cohorts in the advanced/metastatic setting. Prior treatment with ADC with topoisomerase inhibitor payload is only allowed for participants in the second-line plus cohorts in the advanced/metastatic setting.
3. Is a candidate to locoregional treatment (including surgical resection, stereotactic radiotherapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control (sometimes described as “radical” intent), per investigator’s assessment.
4. Has a history of significant hematologic toxicity to prior lines of therapy, as assessed by investigator, e.g., Grade 4 febrile neutropenia or recurrent/persistent Grade 3 to 4 neutropenia.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Part 1 - Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period
2. Part 1 - Occurrence of Treatment-emergent adverse events (TEAEs), serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs from the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
3. Part 1 - Occurrence of dose interruption, reduction, and treatment discontinuations due to TEAEs by dose level from the time of the first dose of IMP to 90 days after the last dose of IMP or until new anticancer therapy is started, whichever occurs first
4. Part 2 cohorts 1 and 2 - Occurrence of TEAEs, serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs from the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
5. Part 2 cohorts 1 and 2 - Occurrence of dose interruption, reduction, and treatment discontinuation due to TEAEs from the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first
6. Part 2 cohorts 1 and 2 - 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 (per response evaluation criteria in solid tumors [RECIST] version v1.1 based on the investigator’s assessment).
7. Part 2 cohorts 3-7 - ORR defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response (per RECIST version v1.1 based on the investigator’s assessment).

Secondary endpoints 9

1. Part 1 - ORR defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response (per RECIST version v1.1 based on the investigator’s assessment).
2. Part 1 - Disease control rate (DCR), defined as the proportion of participants with confirmed CR, PR, or stable disease (SD) as best overall response (per RECIST version v1.1 based on the investigator’s assessment).
3. Part 2 all cohorts - PFS defined as the time from first dose of IMP to the first objective tumor progression (PD) or death from any cause, whichever occurs first, per RECIST v1.1 based on the investigator’s assessment.
4. Part 2 all cohorts - Duration of response (DOR), defined as the time from first objective response (CR or PR) to first occurrence of objective tumor progression (PD) or death from any cause, whichever occurs first (per RECIST v1.1 based on the investigator’s assessment).
5. Part 2 all cohorts - Overall survival (OS), defined as the time from first dose of IMP to death from any cause.
6. Part 2 all cohorts - DCR, defined as the proportion of participants with confirmed CR, PR, or SD as best overall response (per RECIST v1.1 based on the investigator’s assessment).
7. Part 2 all cohorts - Time to response (TTR), 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)
8. Part 2 cohorts 3-7 - Occurrence of TEAEs, serious TEAEs, treatment-related TEAEs, and treatment-related serious TEAEs from the time of the first dose of IMPs to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first.
9. Part 2 cohorts 3-7 - Occurrence of dose interruption, reduction, and treatment discontinuation due to TEAEs from the time of the first dose of IMP to 90 days after the last IMP dose or until new anticancer therapy is started, whichever occurs first

Investigational products

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

Test 2

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 11

Locations

4 EU/EEA countries · 26 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 31 files

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

Application history

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