A Clinical Trial to Test if the Investigational Drug BNT329 is Safe and Potentially Beneficial for People With Advanced Solid Tumors Known to Express the Tumor Marker CA19-9

First-in-human, Open-label, Multi-site, Phase I/IIa, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of BNT329 in Participants With Advanced Solid Tumors Known to Express CA19-9

The main goal of this study is to evaluate the safety of BNT329 and to identify the best dose of BNT329. This will be done by measuring the number of side effects that participants experience and how severe they are.

The second goal of this study is to evaluate how well BNT329 works. This will be done by measuring the number of participants who respond to the treatment. The length of time where the tumor does not grow or spread will also be measured.

The study will also evaluate how BNT329 moves into, through, and out of the body and how the treatment affects the body.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Cancers
• Intervention / Treatment: Drug: BNT329; Drug: CA19-9-targeting monoclonal antibody

Detailed Description

The study will consist of up to four parts (Parts A, B, C, and D).

Parts A and B will be a dose escalation to investigate the safety and tolerability of BNT329. Parts A and B will enroll participants with the following advanced solid tumors known to express carbohydrate antigen 19-9 (CA19-9): pancreatic ductal adenocarcinoma (PDAC) (the most common type of pancreatic cancer), bile duct cancer, a certain type of bladder cancer that started in the lining of the bladder or urinary tract (invasive urothelial carcinoma of the bladder and urinary tract), colorectal cancer, gastroesophageal junction cancer, gastric adenocarcinoma, endometrial cancer, or ovarian cancer. The cancer must not have responded well to previous treatments.

The study will start with recruitment into Part A. Part B (testing a more frequent dosing schedule) will only be opened if indicated by cumulative data from Part A of the study.

Part C (testing pre-dosing with a CA19-9 targeting monoclonal antibody prior to BNT329 administration) will only be opened in case of unforeseen safety and/or weak efficacy signals are detected in Part A and (if opened) Part B. Details on Part C will be added in a future update, if it is necessary, to open this part.

Part D will be a dose optimization and proof-of-concept study to further investigate the safety and tolerability of BNT329 and to investigate preliminary anti-tumor activity. Part D will enroll participants with second-line plus PDAC.

Parts A, B, and C will be non-randomized. In Part D, participants will be randomized (1:1) into one of two arms which will evaluate two dose levels (as selected from Parts A and B).

The study consists of a screening period, a treatment period, an end of treatment visit, two safety follow-up visits, and a survival follow-up period. The treatment period will last for a maximum of 2 years. Participants will remain in the survival follow-up until death, withdrawal of participant's consent, or termination of the study, whichever occurs first.

• Study Type: Interventional
• Enrollment (Estimated): 245
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: BioNTech clinical trials patient information; Phone Number: +49 6131 9084; Email: patients@biontech.de

Study Locations

• Australia
  • Clayton, Australia, 3168
    • Recruiting
    • Monash Health
  • Heidelberg, Australia, 3084
    • Recruiting
    • Austin Health
• Germany
  • Bochum, Germany, 44791
    • Recruiting
    • St. Josef-Hospital im Katholischen Klinikum Bochum
  • München, Germany, 81377
    • Recruiting
    • Klinikum der Universität München
  • Ulm, Germany, D-89081
    • Recruiting
    • Universitaetsklinikum Ulm
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Logroño, Spain, 26006
    • Recruiting
    • Hospital San Pedro
  • Madrid, Spain, 28050
    • Recruiting
    • Hospital Universitario HM Sanchinarro - START Madrid CIOCC
  • Pozuelo de Alarcón, Spain, 28223
    • Recruiting
    • Hospital Universitario Quironsalud Madrid - NEXT Oncology
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • St James´s University Hospital
  • London, United Kingdom, NW3 2QG
    • Recruiting
    • Royal Free Hospital
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Recruiting
    • Northern Centre for Cancer Research
  • Sutton, United Kingdom, SM2 5PT
    • Recruiting
    • The Royal Marsden Hospital
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • SCRI at HCA Health One
  • Florida
    • Orlando, Florida, United States, 32827
      • Recruiting
      • Florida Cancer Specialists
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria

All participants and parts:

• Have an Eastern Cooperative Oncology Group performance score of 0 to 1
• Have measurable disease per RECIST v1.1, except for ovarian cancer where participants will be evaluated according to Gynecologic Cancer InterGroup criteria.
• Have a life expectancy of ≥3 months in the opinion of the investigator.
• Have adequate organ, coagulation, and hematologic function as defined in the protocol.

Parts A, B, and C:

• Have a histologically confirmed advanced/metastatic tumor type that is known to express CA19-9: PDAC, carcinoma of the bile ducts, invasive urothelial carcinoma of the bladder and urinary tract, colorectal adenocarcinoma, adenocarcinoma of the esophagogastric junction, gastric adenocarcinoma, endometrial carcinoma, and epithelial ovarian cancer (including adenocarcinoma of the fallopian tube and peritoneal epithelial cancer [except mesothelioma]).
• Have no available standard of care therapy likely to confer clinical benefit in the opinion of the investigator. Participants must have received all available standard therapies, including targeted therapies based on mutation status (per guidelines from the Food and Drug Administration, American Society of Clinical Oncology, European Society for Medical Oncology, or local guidelines used at the site), and failed at least first-line standard of care therapy prior to enrollment.

Part D:

• Have a histologically confirmed diagnosis of PDAC.
• Must have been offered all available standard therapies including targeted therapies based on mutation status. Established second-line therapies available must not be withheld.
• Have radiographic disease progression and no available standard of care therapy likely to confer clinical benefit in the opinion of the investigator.

Key Exclusion Criteria

All participants and parts:

• Are enrolled in another investigational study or are subject to exclusion periods from another investigational study.
• Have had an inadequate washout period for prior anticancer treatment prior to the first dose of investigational medicinal product (IMP) as defined in the protocol.

• Have received systemic steroids (>10 mg/day of prednisone or its equivalent) or other immunosuppressive therapy within 2 weeks prior to the first dose of IMP. The following are exceptions to this criterion:

  • Inhaled sprays, topical steroids, or local steroid injections (e.g., intra-articular injection).
  • Systemic steroids at physiological doses as replacement therapy (e.g., physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency).
  • Steroids as pre-medication for hypersensitivity reactions (e.g., computed tomography (CT) scan pre-medication).
• Have received any live vaccine within 4 weeks prior to the first dose of IMP or intend to receive a live vaccine during the study.
• Have brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anticonvulsants for at least 2 weeks prior to the first dose of IMP.
• Have a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Have active gastric and duodenal ulcers, ulcerative colitis, or other gastrointestinal conditions that may cause bleeding or perforation in the opinion of the treating investigator.
• Have an active infection that requires systemic therapy within 1 week prior to the first dose of IMP. Participants receiving prophylactic anti-infective therapy (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) may be eligible after discussion with the sponsor.
• Have unresolved toxicities from previous anticancer therapy as defined in the protocol.

NOTE: Other protocol defined inclusion/exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation - Part A; BNT329 administered once every 3 weeks at protocol-defined dose levels	Drug: BNT329; Intravenous (IV) infusion
Experimental: Dose Escalation - Part B; BNT329 administered once every 2 weeks at protocol-defined dose levels	Drug: BNT329; Intravenous (IV) infusion
Experimental: Dose Escalation: Part C; BNT329 administered after pre-dosing with a CA19-9 targeting monoclonal antibody	Drug: BNT329; Intravenous (IV) infusion; Drug: CA19-9-targeting monoclonal antibody; Monoclonal antibody
Experimental: Dose Expansion - Part D; Participants will be randomized to one of two arms evaluating two different doses as selected from Parts A, B, and/or C	Drug: BNT329; Intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A and B - Occurrence of dose-limiting toxicities within a participant	Per dose level.	First 21 days (Part A) or 28 days (Part B) after the first dose of BNT329.
Parts A, B, and D - Occurrence of treatment-emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious adverse events (SAEs), treatment-related TEAEs, treatment-related Grade ≥3 TEAEs, and treatment-related SAEs	Per dose level.	From first dose of BNT329 until 60 days after the last dose of BNT329 (up to 26 months).
Parts A, B, and D - Occurrence of dose interruptions, reductions, and discontinuation of BNT329 due to TEAEs	Per dose level.	From the time of initiation of the first dose of BNT329 until 60 days after the last dose of BNT329 (up to 26 months).
Part D - Objective response rate (ORR)	Per dose level. Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (based on the investigator's assessment) is observed as best overall response.	From first dose of BNT329 until end of study (up to approximately 36 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A, B, and D - Assessment of area under the curve derived from serum/plasma concentrations of CA19-9-unbound ADC, CA19-9-unbound total anti-CA19-9 antibody, and unconjugated YL0010014 payload	Per dose level (if data permit)	First 21 days (Part A) or 28 days (Part B) after the first dose of BNT329.
Parts A, B, and D - Assessment of maximum concentration derived from serum/plasma concentrations of CA19-9-unbound ADC, CA19-9-unbound total anti-CA19-9 antibody, and unconjugated YL0010014 payload	Per dose level (if data permit).	First 21 days (Part A) or 28 days (Part B) after the first dose of BNT329.
Parts A, B, and D - Assessment of time to reach maximum concentration derived from serum/plasma concentrations of CA19-9-unbound ADC, CA19-9-unbound total anti-CA19-9 antibody, and unconjugated YL0010014 payload	Per dose level (if data permit).	First 21 days (Part A) or 28 days (Part B) after the first dose of BNT329.
Parts A, B, and D - Assessment of terminal half-life derived from serum/plasma concentrations of CA19-9-unbound ADC, CA19-9-unbound total anti-CA19-9 antibody, and unconjugated YL0010014 payload	Per dose level (if data permit).	First 21 days (Part A) or 28 days (Part B) after the first dose of BNT329.
Parts A and B - ORR	Per dose level. Defined as the proportion of participants in whom a confirmed CR or PR (based on the investigator's assessment) is observed as best overall response.	From first dose of BNT329 until end of study (up to approximately 36 months).
Parts A, B, and D - Disease control rate	Per dose level. Defined as the proportion of participants in whom a CR or PR or stable disease (assessed at least 6 weeks [±2 days] after the first BNT329 dose) is observed as best overall response per investigator's assessment.	From first dose of BNT329 until end of study (up to approximately 36 months).
Parts A, B, and D - Duration of response	Per dose level. 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.	From first dose of BNT329 until end of study (up to approximately 36 months).
Parts A, B, and D - Progression free survival	Per dose level. Defined as the time from first dose of BNT329 to first objective tumor progression (PD per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1] based on the investigator's assessment), or death from any cause, whichever occurs first.	From first dose of BNT329 until end of study (up to approximately 36 months).
Part D - Overall survival	Per dose level. Defined as the time from first dose of BNT329 to death from any cause.	From first dose of BNT329 until end of study (up to approximately 36 months).
Parts A, B, and D: Anti-drug antibody (ADA) prevalence	Per dose level/cohort. Defined as the proportion of participants who are ADA positive at any timepoint (either baseline or post-baseline) (if data permit).	From first dose of BNT329 until up to 60 days after the last dose of BNT329 (up to 26 months).
Parts A, B, and D - ADA incidence	Per dose level/cohort. Defined as the proportion of participants having treatment-emergent ADA (if data permit).	From first dose of BNT329 until up to 60 days after the last dose of BNT329 (up to 26 months).

Collaborators and Investigators

• Sponsor: BioNTech SE
• Investigators: Study Director: BioNTech Response Person, BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2025
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: September 16, 2025
• First Submitted That Met QC Criteria: September 16, 2025
• First Posted (Actual): September 22, 2025

Study Record Updates

• Last Update Posted (Actual): August 27, 2026
• Last Update Submitted That Met QC Criteria: August 26, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal cancer; Ovarian cancer; Gastroesophageal junction cancer; Gastric adenocarcinoma; Pancreatic ductal adenocarcinoma; Endometrial cancer; CA19-9; Bile duct cancer; Anti-drug conjugate (ADC); Invasive urothelial carcinoma of the bladder and urinary tract
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Uterine Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Biliary Tract Diseases; Colonic Diseases; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Uterine Neoplasms; Bile Duct Diseases; Biliary Tract Neoplasms; Colorectal Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms; Bile Duct Neoplasms
• Other Study ID Numbers: BNT329-01; 2025 (U.S. NIH Grant/Contract: Faculty of Social Sciences Scientific Grant at the University of Gdańsk); 2025-522613-26-00 (Ctis); 1012877 (Other Identifier: United Kingdom (UK) integrated research application system (IRAS))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No