BNT3214 for adults with advanced solid tumors

A Phase I/IIa, First-in-human, Open-label, Multi-site, Multi-regional, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of BNT3214 in Adults With Advanced Solid Tumors

This trial will test whether the experimental drug BNT3214 is safe and shows signs of benefit for adults whose advanced solid tumors have progressed after standard treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 533 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: BioNTech SE (Industry-sponsored)
• Drugs / interventions: immunotherapy, prednisone
• Locations: 4 sites (Fitzroy and 3 other locations)
• Trial ID: NCT07455734 on ClinicalTrials.gov

What this trial studies

This first-in-human, multi-part trial uses dose-escalation (Parts A and optional B) to identify safe and tolerable dose levels of BNT3214 and then tests selected doses across multiple tumor types in dose-expansion cohorts (Part C). Parts A and B focus on safety, tolerability, pharmacokinetics, and early response signals, while Part C enrolls indication-specific cohorts and includes a randomized dose-optimization subcohort. No randomization is used in Parts A, B, or most dose-expansion cohorts, and treatment continues up to 2 years or until progression, unacceptable toxicity, or other discontinuation criteria. An internal review committee will review accumulating safety and efficacy data to recommend dose levels and cohort expansion decisions.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically or cytologically confirmed locally advanced, recurrent, or metastatic solid tumors, measurable disease by RECIST v1.1, ECOG performance status 0–1, adequate organ function, and disease that progressed after at least one available standard therapy are the intended participants.

Not a fit: Patients with poor performance status (ECOG >1), inadequate organ function, a life expectancy under three months, or those for whom standard effective treatments remain available are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, BNT3214 could provide a new treatment option that shrinks or slows progression of some advanced solid tumors that have stopped responding to standard therapies.

How similar studies have performed: While other bispecific antibodies and immune checkpoint approaches have shown activity in some cancers, BNT3214 is being tested in humans for the first time and its clinical effects are unproven.

Eligibility criteria

Inclusion Criteria:

* Participants aged ≥18 years of age inclusive at the time of giving informed consent.
* Have at least one measurable tumor lesion based on RECIST v1.1. One lesion with prior local treatment (i.e., radiotherapy) can be considered measurable only if a disease progression from prior local treatment was demonstrated in the lesion per RECIST v1.1.
* Eastern Cooperative Oncology Group performance status of 0 or 1.
* Have a predicted life expectancy ≥3 months.
* Have histologically or cytologically confirmed locally advanced, recurrent, or metastatic solid tumors that have progressed after at least one available standard therapy; or for whom the standard therapy is considered to be ineffective, inappropriate or intolerable; or for whom a clinical study of an investigational agent is a recognized standard of care.
* Have adequate liver function as defined in the protocol.
* Have adequate renal function as defined in the protocol.
* Have adequate hematologic function as defined in the protocol.
* Have adequate coagulation as defined in the protocol.

Exclusion Criteria:

* Untreated or symptomatic central nervous system (CNS) metastases and leptomeningeal disease.
* Have a primary CNS malignancy.
* Have active, or a history of, pneumonitis requiring treatment with steroids, or have active, or a history of, interstitial lung disease.
* Have clinically significant pulmonary complications including, but not limited to, chronic obstructive pulmonary disease, restrictive lung disease, lung injury accompanied with autoimmune disease/connective tissue disorders.
* Have a history of severe cardiovascular disease.
* Have a history of significant hematologic toxicity to prior lines of therapy, as assessed by the investigator.
* Have uncontrolled hypertension or poorly controlled diabetes prior to allocation or randomization.
* Have concurrent malignancy within 5 years prior to allocation or randomization (protocol defined exceptions apply).
* Have unstable thrombotic event (e.g., deep vein thrombosis, arterial thrombosis, pulmonary embolism) requiring therapeutic intervention within 3 months prior to allocation or randomization, unless the participant has been fully treated (e.g., inferior vena cava filter placed) and/or adequately anticoagulated on a prophylactic dose.
* Have known human immunodeficiency virus infection or known acquired immunodeficiency syndrome (protocol defined exceptions apply).
* Have an active hepatitis B virus infection.
* Have an active hepatitis C virus (HCV) infection. Participants with a negative HCV antibody test at screening or positive HCV antibody test followed by a negative HCV ribonucleic acid test at screening are eligible. Participants who have completed curative antiviral treatment with HCV viral load below the limit of quantification are allowed.
* Have adverse reactions from prior anti-tumor therapy that have not returned to Grade ≤1, except for alopecia or toxicities (not specified elsewhere) considered irreversible and posing no safety risk to participants.
* Have active, or history of, autoimmune disease (e.g., myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, vasculitis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis) (protocol defined exceptions apply).
* Have serious non-healing wounds, ulcer, or bone fracture.
* Participants with lung cancer who have major coagulation disorders or an increased risk of hemorrhage (per investigator's clinical judgment)
* Have a history of serious Grade ≥3 immune-related adverse events (irAEs) that led to treatment discontinuation of a prior immunotherapy. Participants with a history of Grade ≥3 irAEs that did not lead to treatment discontinuation of a prior immunotherapy should be evaluated and determined by investigators for potential safety risk.
* Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to allocation or randomization.
* Current or prior use of immunosuppressive medication within 14 days before the first dose of study treatment (protocol defined exceptions apply).
* Have received any of the following therapies or drugs within the noted time intervals prior to allocation or randomization:

  * Systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 10 days prior to the initiation of study treatment.
  * Have been vaccinated with live, attenuated vaccine(s) within 4 weeks prior to initiation of the study treatment.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Where this trial is running

Fitzroy and 3 other locations

• Monash Medical Centre Clayton — Fitzroy, Australia (Not_yet_recruiting)
• Epworth HealthCare — Richmond, Australia (Not_yet_recruiting)
• Shanghai East Hospital — Shanghai, China (Recruiting)
• National Taiwan University Hospital — Taipei, Taiwan (Not_yet_recruiting)

Study contacts

• Study coordinator: BioNTech clinical trials patient information

Conditions Advanced Solid Tumor Cancer; Advanced solid tumors; Bispecific antibody; Immune checkpoint inhibitor