A First-in-human, Dose Escalation and Indication Expansion Study of BNT3212 as Monotherapy or in Combination With BNT327 in Adults With Advanced Solid Tumors

NCT07147348 | Recruiting Phase 1 DMC

• 1 other identifier: BNT3212-01
• Study Type: interventional
• Target: 375
• Locations: 2 countries
• Sites: 2

Brief Summary

The aim of this first-in-human (FIH) open-label, multi-site study is to evaluate safety, tolerability, pharmacokinetics (PK), immunogenicity and preliminary clinical efficacy of BNT3212, including identification of the recommended dose of BNT3212 for use as monotherapy and with BNT327 as combination therapy, in adults with advanced solid tumors who have exhausted other treatment options.

Conditions

Advanced Solid Tumor

Keywords

BNT3212 (or PM1300); BNT327; Programmed death-ligand 1 (PD-L1); Vascular endothelial growth factor A (VEGF-A); Bispecific antibody; Antibody-drug conjugate (ADC); Combination with other investigational agents; Immunotherapy; Antibody; Programmed death 1 (PD-1)

Outcome Measures

Primary Outcomes (4)

• Parts A and C - Occurrence of dose limiting toxicities (DLTs) within a participant during the DLT observation period

  Per cohort.

  Until 28 days after first dose of investigational medicinal product (IMP).

• All parts - Percentage of participants with treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs by relationship

  Per cohort. Adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for AEs version 5.0 (NCI CTCAE v5.0).

  From the time of the first dose of IMP until 90 days after the last dose of IMP, approximately up to 31 months.

• Parts A and C - Percentage of participants with dose interruptions or discontinuations of study treatment due to TEAEs

  Per cohort.

  From the time of the first until last dose of IMP, approximately up to 31 months.

• Parts B and D - Percentage of participants with dose interruptions, reductions or discontinuations of study treatment due to TEAEs

  Per cohort.

  From the time of the first until last dose of IMP, approximately up to 31 months.

Secondary Outcomes (11)

• All parts - PK assessment: Maximum concentration (Cmax) derived from serum/plasma concentrations

  From predose to 28 days after first dose of IMP.

• All parts - PK assessment: Area under the concentration-time curve (AUC0-t) derived from serum/plasma concentrations

  From predose to 28 days after first dose of IMP.

• All parts - PK assessment: Minimum concentration (Ctrough) derived from serum/plasma concentrations

  From predose until 90 days after the last dose of IMP.

• All parts - Anti-drug antibody (ADA) prevalence

  For up to 90 days from the last dose of IMP.

• All parts - ADA incidence

  For up to 90 days from the last dose of IMP.

Study Arms (8)

Part A - BNT3212 monotherapy (dose escalation)

EXPERIMENTAL

Escalating dose levels of BNT3212 to define the maximum tolerated dose (MTD) in participants with histologically or cytologically confirmed locally advanced/unresectable, recurrent, or metastatic malignant solid tumors who are refractory to or unable to tolerate standard treatment, or for whom no standard treatment is available.

Biological: BNT3212

Part B - BNT3212 monotherapy dose level (DL)1 (expansion cohort)

EXPERIMENTAL

Indication-specific cohort populations will be tested.

Biological: BNT3212

Part B - BNT3212 monotherapy DL2 (expansion cohort)

EXPERIMENTAL

Indication-specific cohort populations will be tested.

Biological: BNT3212

Part B - BNT3212 monotherapy DL3 (expansion cohort)

EXPERIMENTAL

Indication-specific cohort populations will be tested.

Biological: BNT3212

Part C - BNT3212 + BNT327 combination therapy (dose escalation)

EXPERIMENTAL

Escalating dose levels of BNT3212 plus a fixed dose of BNT327 to define the MTD in participants with histologically or cytologically confirmed locally advanced/unresectable, recurrent, or metastatic malignant solid tumors who are refractory to or unable to tolerate standard treatment, or for whom no standard treatment is available.

Biological: BNT3212; Biological: BNT327

Part D - BNT3212 DL1 + BNT327 combination therapy (expansion cohort)

EXPERIMENTAL

Indication-specific cohort populations will be tested.

Biological: BNT3212; Biological: BNT327

Part D - BNT3212 DL2 + BNT327 combination therapy (expansion cohort)

EXPERIMENTAL

Indication-specific cohort populations will be tested.

Biological: BNT3212; Biological: BNT327

Part D - BNT3212 DL3 + BNT327 combination therapy (expansion cohort)

EXPERIMENTAL

Indication-specific cohort populations will be tested.

Biological: BNT3212; Biological: BNT327

Interventions

BNT3212 BIOLOGICAL

Intravenous infusion

Part A - BNT3212 monotherapy (dose escalation); Part B - BNT3212 monotherapy DL2 (expansion cohort); Part B - BNT3212 monotherapy DL3 (expansion cohort); Part B - BNT3212 monotherapy dose level (DL)1 (expansion cohort); Part C - BNT3212 + BNT327 combination therapy (dose escalation); Part D - BNT3212 DL1 + BNT327 combination therapy (expansion cohort); Part D - BNT3212 DL2 + BNT327 combination therapy (expansion cohort); Part D - BNT3212 DL3 + BNT327 combination therapy (expansion cohort)

BNT327 BIOLOGICAL

Intravenous infusion

Part C - BNT3212 + BNT327 combination therapy (dose escalation); Part D - BNT3212 DL1 + BNT327 combination therapy (expansion cohort); Part D - BNT3212 DL2 + BNT327 combination therapy (expansion cohort); Part D - BNT3212 DL3 + BNT327 combination therapy (expansion cohort)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with 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 inappropriate or intolerable.
• Have at least one measurable lesion based on RECIST v1.1.
• Eastern Cooperative Oncology Group performance status of 0 (fully active, able to carry out all pre-disease activities without restriction) or 1 (unable to perform physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature).
• Predicted life expectancy of ≥3 months.
• Left ventricular ejection fraction ≥50% by either echocardiography or multigated acquisition scan within 28 days prior to first dose of study treatment.
• Adequate liver, renal, hematological, and coagulation function.
• Recovery to Grade 0-1 (or baseline) from adverse reactions related to prior anti cancer therapy except for:
• Asymptomatic laboratory abnormalities such as elevated alkaline phosphatase, hyperuricemia, elevated serum amylase/lipase, and elevated blood glucose.
• Toxicity that the investigator determined to have no safety risk, such as alopecia, Grade 2 peripheral neurotoxicity, hypothyroidism stabilized by hormone replacement therapy, etc.
• The investigator considers discontinuation of protocol-defined anti-cancer therapies and restricted medications with protocol-defined washout periods as medically acceptable.
• For Parts B and D only: Participants must be diagnosed with specific indications.

You may not qualify if:

• Active infection (e.g., bacterial or fungal infections) requiring systemic treatment (e.g., severe pneumonia, bacteremia, sepsis), except oral antibiotics.
• Participants with primary central nervous system (CNS) malignancies.
• Active CNS metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
• Unstable pleural effusion or ascites requiring thoracentesis or paracentesis within 14 days prior to initiation of study treatment.
• Have active, or a history of, pneumonitis requiring treatment with steroids, or has active, or a history of, interstitial lung disease.
• Clinically significant pulmonary complications.
• History of severe cardiovascular disease.
• Have a history of significant hematologic toxicity to prior lines of therapy, as assessed by investigator, e.g., Grade 4 febrile neutropenia or recurrent/persistent Grade 3 to 4 neutropenia.
• Have active or chronic corneal disorders or with any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.
• Have uncontrolled hypertension while on antihypertensive medicine or poorly controlled diabetes.
• Concurrent malignancy within 5 years prior to study enrollment. Exceptions: basal cell carcinoma, squamous cell carcinoma of the skin, carcinoma in situ after radical resection.
• Unstable thrombotic event (e.g., deep vein thrombosis, arterial thrombosis, pulmonary embolism).
• Have adverse reactions from prior anti-tumor therapy that have not returned to Grade 1 (graded by NCI CTCAE v5.0 criteria) or below (unless the investigator determines that certain AEs pose no safety risk to participants, such as hair loss, Grade 2 peripheral neuropathy or stable hypothyroidism under hormone replacement therapy) are not eligible for the study.
• For Parts C and D only: Prior treatment with PD-1/L1 and VEGF-A antibody combinations (including bispecific antibodies to PD-1/L1 and VEGF-A).
• For Parts C and D only: Have active, or history of, autoimmune disease with risk of exacerbation following PD-L1 inhibition OR an immune deficiency (e.g., allogeneic hematopoietic stem cell transplantation or organ transplantation). Participants with protocol-specified conditions may be eligible.

Sponsors & Collaborators

• BioNTech SE: lead
• Biotheus (Hengqin) Co., Ltd.: collaborator
• BioNTech (Shanghai) Pharmaceuticals Co., Ltd.: collaborator

Study Sites (2)

Scientia Clinical Research Limited

Randwick, 2031, Australia

NOT YET RECRUITING

Shanghai East Hospital

Shanghai, 200120, China

RECRUITING

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Central Study Contacts

: BioNTech clinical trials patient information

CONTACT

+49 6131 9084; patients@biontech.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2025
• First Posted: August 29, 2025
• Study Start: August 27, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); CN (1)