A clinical study to test if an investigational treatment called BNT326 is safe and potentially beneficial when used alone or in combination with other investigational treatments such as BNT327, for people with advanced malignant tumors

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

5 Dec 2025 → ongoing

Decision date (initial)

2025-10-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BioNTech SE

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Dose response

Part 1 (monotherapy): To assess safety and efficacy of BNT326 monotherapy according to RECIST 1.1.
Part 2 (combination therapy): To assess safety and efficacy of BNT326 in each combination treatment with immunotherapy (e.g., BNT327) according to RECIST 1.1.

Secondary objectives 3

1. Parts 1 and 2: To evaluate the efficacy of BNT326 (other than objective response rate (ORR)) as monotherapy and in each combination treatment with immunotherapy (e.g., BNT327).
2. Parts 1 and 2: To assess the pharmacokinetics (PK) of BNT326 as monotherapy and in each combination treatment with immunotherapy (e.g., BNT327).
3. Parts 1 and 2: To evaluate immunogenicity of BNT326 as monotherapy and in each combination treatment with immunotherapy (e.g., BNT327).

Conditions and MedDRA coding

Advanced solid tumors

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Participants need to be able to give informed consent and have given written consent in accordance with International Conference on Harmonisation Good Clinical Practice (ICH GCP) and local legislation prior to the start of any trial-specific procedures.
2. Participants are willing and able to comply with scheduled visits, treatment schedule, the planned trial assessments, lifestyle restrictions, and other requirements of the trial. This includes that they can understand and follow trial-related instructions.
3. Participants must be 18 years of age or older at the time of giving informed consent. Local laws will be followed if the age of consent is older.
4. Have histologic or cytologic documented advanced disease, either at relapse or upon diagnosis of metastatic disease.
5. Have measurable disease defined by RECIST 1.1.
6. All participants must provide a tumor tissue sample (FFPE slides) from archival tissue. The archival tissue can be an FFPE block or freshly cut slides derived from the advanced setting. If archival tissue is not available, a fresh biopsy must be collected, collection must be before Cycle 1 Day 1. Details are provided in the Laboratory Manual. If a tumor tissue sample cannot be provided, enrollment depends on approval by the sponsor’s medical monitor.
7. Have ECOG performance status of 0 or 1.
8. Have adequate organ and bone marrow function within 7 days before randomization/enrollment.
9. Have had an adequate washout period of previous treatments before randomization/enrolment.
10. For Part 2 only: Qualitative urine protein ≤1+. If qualitative urine protein is ≥2+, a 24 h urine protein quantitative test is required. If the 24 h urine protein result is <1 g, participants can be enrolled.
11. Agree not to enroll in another clinical trial of an investigational medicinal product (IMP), starting at the time of giving informed consent and continuously until the last planned visit in this trial.
12. People of child-bearing potential (POCBP) who have a negative serum β-hCG pregnancy test, agree to practice a highly effective form of contraception, require their potentially fertile male partners to use condoms, and agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the trial.
13. Men who are sterile, or if they are potentially fertile and sexually active with a partner of child-bearing potential, agree to use condoms and to ask their sexual partners to practice a highly effective form of contraception during the trial, and are willing to refrain from sperm donation.
14. Fulfil the cohort-specific inclusion criteria as detailed in the trial protocol.

Exclusion criteria 30

1. Prior treatment with an agent targeting HER3 (including antibody, antibody-drug conjugates (ADCs), cell therapy, and other drugs).
2. Have active or chronic corneal disorders or any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.
3. Are a candidate to locoregional treatment (including surgical resection, stereotactic radiation therapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control, per investigator’s assessment.
4. Have a known history or a positive test at screening of HIV 1 or 2 infection or hepatitis B infection. Participants with a negative hepatitis C virus (HCV)-antibody test at screening or positive HCV antibody test followed by a negative HCV RNA test at screening are eligible.
5. Have unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than alopecia) not yet resolved to at or below Grade 1 or baseline.
6. Are POCBP who are pregnant or breastfeeding or are planning pregnancy or potentially fertile males, who are planning to father children.
7. Have a history of allergies, hypersensitivities, or intolerance to the trial treatments including any excipients thereof.
8. Have a history of intolerance to treatment with a topoisomerase I inhibitor or intolerance to an ADC that consists of a topoisomerase I inhibitor, including but not limited to topotecan, irinotecan, and deruxtecan (DXd) (e.g., severe diarrhea).
9. Have 24-h urine protein excretion of 1 g or more.
10. Have a history of Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior checkpoint inhibitor.
11. Have active or a history of autoimmune disease with a risk of exacerbation following PD-L1 inhibition or have an immune deficiency.
12. Have received any IMP within 28 days or five half-lives if known (whichever is longer) before administration of first dose of IMP or are participating in the active treatment period of another interventional clinical trial.
13. Have serious non-healing wounds, ulcers, or bone fractures.
14. Have hypertension or diabetic conditions prior to trial treatment including people with a history of hypertensive crisis or hypertensive encephalopathy.
15. Have a history of significant hematologic toxicity to prior lines of therapy, as assessed by investigator.
16. Have an uncontrolled concomitant or intercurrent illness, that contra-indicates trial participation, limits compliance with trial procedures or substantially increases the risk of incurring adverse events (AEs).
17. Have active or have a history of uncontrolled or significant cardiovascular disease.
18. Have left ventricular ejection fraction (LVEF) below 50% by either ECHO or MUGA within 28 days before randomization/enrollment.
19. 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.
20. 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.
21. Have a history of another primary malignancy within 2 years or have a known additional malignancy that is progressing or requires treatment.
22. Have a medical, psychological, or social condition or substance abuse 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.
23. Have a history of any of prior immunosuppressive medication within 14 days prior to first dose of IMP or prior live-attenuated vaccine within 30 days prior to the first dose of IMP, or prior randomization or treatment in a previous trial with the same IMPs as the current trial, regardless of treatment assignment.
24. Are subject to exclusion periods from another investigational 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.
26. Are fulfilling any of the cohort-specific exclusion criteria as detailed in the trial protocol.
27. Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
28. Have clinically active central nervous system metastases.
29. Participants with significant risks of hemorrhage or evidence of major coagulation disorders.
30. Have a history of intolerance to treatment with an anti-VEFG, anti-PD-1/PDL-1, or similar substance, including, but not limited to, bevacizumab, ramucirumab, atezolizumab, pembrolizumab, nivolumab, or other related therapies.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. For Part I (monotherapy): Occurrence of treatment-emergent adverse events (TEAEs), treatment-emergent related adverse events (TRAEs), treatment-emergent serious adverse events (TESAEs), and treatment-emergent related serious adverse events (TRSAEs), by cohort and dose, from the time of initiation of the first dose of IMP to 42 days after the last dose of IMP or until a new anti-cancer therapy is started.
2. For Part I (monotherapy): Occurrence of dose interruption, reduction, and treatment discontinuations due to TEAEs, by cohort and dose, from the time of initiation of the first dose of IMP to 42 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first.
3. For Part I (monotherapy): Confirmed objective response rate (ORR), defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) based on the investigator’s assessment (per RECIST 1.1) is observed as best overall response, by cohort and dose.
4. Part 2 (combination therapy): Occurrence of treatment-emergent adverse events (TEAEs), treatment-emergent related adverse events (TRAEs), treatment-emergent serious adverse events (TESAEs), and treatment-emergent serious related adverse events (TRSAEs), and dose interruption, reduction, and discontinuation due to TEAEs, by cohort and dose.
5. Part 2 (combination therapy): Occurrence of dose-limiting toxicities (DLTs) during the DLT observation period.
6. Part 2 (combination therapy): Confirmed objective response rate (ORR), defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on the investigator’s assessment, is observed as best overall response, by cohort and combination treatment regimen.

Secondary endpoints 8

1. Parts 1 and 2: Progression-free survival (PFS), based on the investigator’s assessment, defined as the time from first dose of IMP to the first objective tumor progression (progressive disease (PD) per RECIST 1.1) or death from any cause, whichever occurs first, by cohort and combination treatment regimen.
2. Parts 1 and 2: Depth of response (DpR) defined as the maximum percent reduction from baseline in tumor size measured by sum of target lesion diameter, by cohort and combination treatment regimen.
3. Parts 1 and 2: Disease control rate (DCR) defined as the proportion of participants with a confirmed complete response (CR), partial response (PR), or a stable disease (per RECIST 1.1 based on the investigator’s assessment) as best overall response, by cohort and combination treatment regimen.
4. Parts 1 and 2: Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1 based on the investigator’s assessment) to first occurrence of objective tumor progression (PD per RECIST 1.1 based on the investigator’s assessment) or death from any cause, whichever occurs first, by cohort and combination treatment regimen.
5. Parts 1 and 2: Time to response (TTR) defined as the time from first dose of IMP to first objective response (CR or PR per RECIST 1.1 based on the investigator’s assessment), by cohort and combination treatment regimen.
6. Parts 1 and 2: Overall survival (OS) defined as the time from first dose of IMP to death from any cause, by cohort and combination treatment regimen.
7. Parts 1 and 2: Pharmacokinetic (PK) parameters derived from serum concentrations of BNT326 ADC, total anti-HER3 antibody component, and unconjugated payload YL0010014 component, by cohort and combination treatment regimen.
8. Parts 1 and 2: Anti-drug antibody (ADA) prevalence and ADA incidence up to 1 year from the last dose of IMP, by cohort and combination treatment regimen.

Investigational products

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

Test 3

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 8

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 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