Early-phase Trial to Assess the Safety and Preliminary Efficacy of BNT3214 in 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 study is the first time the drug BNT3214 (also referred to as PM8102) will be tested in people. It is designed to find out if the drug is safe and how well it works for adults with advanced solid tumors. The study will have three parts. The first two parts (Parts A and B) will focus on testing different amounts of BNT3214 to figure out the best and safest dose. The third part (Part C) will test selected doses of BNT3214 in multiple types of cancer.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor Cancer
• Intervention / Treatment: Drug: BNT3214

Detailed Description

Parts A and B will investigate the safety and tolerability of BNT3214. Part B is optional and will only be opened if emerging data from Part A indicates that an alternative BNT3214 dosing schedule may have a better benefit-risk profile for further development. Based on the available safety, pharmacokinetics (PK) or preliminary overall response data from Parts A and B, the study may progress to Part C. A study internal review committee will oversee the study to evaluate safety data as the study progresses and/or may recommend the dose levels (DLs) for the dose expansion, possible changes in the schedule of dosing, and expansion indications based on the totality of available data.

There will be no randomization in Parts A and B or the dose expansion cohorts of Part C. In the dose optimization cohorts of Part C, eligible participants will be randomized to one of two DLs selected from Parts A and B. In the dose expansion cohorts, participants will be enrolled into indication-specific cohorts as predefined or may be adjusted per safety, efficacy signals from Parts A and/or B.

Participants will receive BNT3214 for a maximum of 2 years or until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), unacceptable toxicity, withdrawal of consent, loss of clinical benefit as determined by the investigator, lost to follow-up, death, or until the sponsor terminates the study or any other criterion for discontinuation is met, whichever occurs first.

• Study Type: Interventional
• Enrollment (Estimated): 533
• 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
  • Fitzroy, Australia, 3065
    • Not yet recruiting
    • Monash Medical Centre Clayton
  • Richmond, Australia, 3121
    • Not yet recruiting
    • Epworth Healthcare
• China
  • Guangzhou, China, 510515
    • Recruiting
    • Nanfang Hospital of Southern Medical University
  • Shanghai, China, 200120
    • Recruiting
    • Shanghai East Hospital
• Taiwan
  • Taipei, Taiwan, 100225
    • Not yet recruiting
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

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

Description

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.

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: Part A - Escalating DLs of BNT3214; Up to 7 DLs of BNT3214. In Part A, participants will stay on the same DL. In DL1 and DL2, intra-participant dose escalation will be allowed at the discretion of the investigator as specified in the protocol.	Drug: BNT3214; Intravenous infusion; Other Names: PM8102
Experimental: Part B (optional) - Selected DLs of BNT3214; Up to 4 DLs. The starting dose for Part B will be at least one DL below the DL that has been declared safe for Part A.	Drug: BNT3214; Intravenous infusion; Other Names: PM8102
Experimental: Part C - Optimized DL of BNT3214; Optimized dose of BNT3214 selected based on totality of data from Parts A and (if conducted) Part B.	Drug: BNT3214; Intravenous infusion; Other Names: PM8102
Experimental: Part C - Dose expansion of BNT3214; DLs as recommended based on the totality of available data from previous parts.	Drug: BNT3214; Intravenous infusion; Other Names: PM8102

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All parts - Number and percentage of participants with treatment emergent adverse events (TEAEs)	Per DL/cohort. By United States National Cancer Institute Common Terminology Criteria for Adverse Events grading, seriousness, and relatedness.	From the time of initiation of the first dose of BNT3214 until 90 days after the last dose of BNT3214
All parts - Number and percentage of participants with dose interruptions, reductions, and discontinuation of BNT3214 due to TEAEs	Per DL/cohort.	Up to 24 months
Parts A and B only - Number and percentage of participants with dose limiting toxicities (DLTs)	During the DLT evaluation period	From first dose up to 28 days
Part C only - Objective response rate (ORR)	Per DL/cohort. Defined as the percentage of participants in whom a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 (based on the investigator's assessment) is observed as best overall response.	Up to 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All parts - PK assessment: Area under the curve (AUC)	Per DL/cohort. Derived for BNT3214 levels in plasma or serum (for Cycle 1, single-dose and Cycle 3, multiple-dose). If data permits.	Up to 3 months from first dose of BNT3214
All parts - PK assessment: Maximum concentration (Cmax)	Per DL/cohort. Derived for BNT3214 levels in plasma or serum (for Cycle 1, single-dose and Cycle 3, multiple-dose). If data permits.	Up to 3 months from first dose of BNT3214
All parts - PK assessment: Time to maximum observed concentration (Tmax)	Per DL/cohort. Derived for BNT3214 levels in plasma or serum (for Cycle 1, single-dose and Cycle 3, multiple-dose). If data permits.	Up to 3 months from first dose of BNT3214
All parts - PK assessment: Half-life (t1/2)	Per DL/cohort. Derived for BNT3214 levels in plasma or serum (for Cycle 1, single-dose and Cycle 3, multiple-dose). If data permits.	Up to 3 months from first dose of BNT3214
Parts A and B only - ORR	Per DL/cohort. Defined as the percentage of participants in whom a confirmed CR or PR per RECIST v1.1 (based on the investigator's assessment) is observed as best overall response.	Up to 30 months
All parts - Disease control rate	Per DL/cohort. Defined as the percentage of participants in whom a confirmed CR or PR or stable disease (assessed at least 6 weeks after the first BNT3214 dose) per RECIST v1.1 (based on the investigator's assessment) is observed as best overall response.	Up to 30 months
All parts - Duration of response	Per DL/cohort. Defined as the time from first objective response (CR or PR) to first occurrence of objective tumor progression (progressive disease) (based on the investigator's assessment) or death from any cause, whichever occurs first.	Up to 30 months
All parts - Anti-drug antibody (ADA) prevalence (percentage of participants who are ADA-positive)	Either baseline or post-baseline. If data permits.	Up to 90 days from the last dose of BNT3214
All parts - ADA incidence (percentage of participants having treatment-emergent ADA)	If data permits.	Up to 90 days from the last dose of BNT3214

Collaborators and Investigators

• Sponsor: BioNTech SE
• Collaborators: BioNTech (Shanghai) Pharmaceuticals Co., Ltd.; Biotheus (Hengqin) Co., Ltd.
• Investigators: Study Director: BioNTech Responsible Person, BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Immune checkpoint inhibitor; Bispecific antibody; Advanced solid tumors
• Other Study ID Numbers: BNT3214-01

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