Testing BNT329 for people with advanced solid tumors that express 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

This will test whether the drug BNT329 is safe and might help people with advanced solid tumors that express the CA19-9 marker.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 245 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: BioNTech SE (Industry-sponsored)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 10 sites (Orlando, Florida and 9 other locations)
• Trial ID: NCT07186842 on ClinicalTrials.gov

What this trial studies

This Phase 1/2, multi-part study starts with dose-escalation cohorts (Parts A–C) to find a safe and tolerable dose of the antibody–drug conjugate BNT329, including exploration of a more frequent dosing schedule and pre-dosing with a CA19-9–targeting antibody. Part D will randomize participants with second-line-or-later pancreatic ductal adenocarcinoma to compare two dose levels chosen from earlier parts to gather preliminary evidence of anti-tumor activity. Key outcomes include rates and severity of side effects, objective tumor responses, progression-free duration, and pharmacokinetics/pharmacodynamics of BNT329. Enrollment focuses on patients with advanced, CA19-9–expressing solid tumors who have limited standard therapy options.

Who should consider this trial

Good fit: Adults with advanced or metastatic solid tumors known to express CA19-9, measurable disease, ECOG performance status 0–1, adequate organ function, and no remaining standard therapies likely to provide clinical benefit.

Not a fit: Patients whose tumors do not express CA19-9, who have ECOG performance status greater than 1, or who have effective standard treatment options available are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, BNT329 could become a new targeted treatment option that shrinks tumors or delays progression in patients with CA19-9–expressing advanced cancers.

How similar studies have performed: Antibody–drug conjugates have shown benefit in some other cancers, but CA19-9–targeted therapies are relatively new and have limited prior clinical proof of concept.

Eligibility criteria

Key Inclusion Criteria

All participants and parts:

* Have an ECOG PS of 0 to 1
* Have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), 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, 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.
* Have received at least one prior systemic treatment regimen for advanced/metastatic disease. Participants who have progressed on \<6 months of (neo)adjuvant chemotherapy can be included in the study.
* 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 requires 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 may apply.

Where this trial is running

Orlando, Florida and 9 other locations

• Florida Cancer Specialists — Orlando, Florida, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
• St. Josef-Hospital im Katholischen Klinikum Bochum — Bochum, Germany (Recruiting)
• Universitaetsklinikum Ulm — Ulm, Germany (Recruiting)
• Hospital Universitari Vall d'Hebron — Barcelona, Spain (Recruiting)
• Hospital San Pedro — Logroño, Spain (Recruiting)
• Hospital Universitario HM Sanchinarro - START Madrid CIOCC — Madrid, Spain (Recruiting)
• Hospital Universitario Quironsalud Madrid - NEXT Oncology — Pozuelo de Alarcón, Spain (Recruiting)
• Northern Centre for Cancer Research — Newcastle upon Tyne, United Kingdom (Recruiting)
• The Royal Marsden Hospital — Sutton, United Kingdom (Recruiting)

Study contacts

• Study coordinator: BioNTech clinical trials patient information

Conditions Advanced Solid Cancers; CA19-9; Anti-drug conjugate; Pancreatic ductal adenocarcinoma; Bile duct cancer; Colorectal cancer; Gastroesophageal junction cancer; Endometrial cancer