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

NCT ID: NCT07147348

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 375 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-27
• Study Completion Date: 2028-03-31

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.

Detailed Description

This study will include four parts (i.e., Parts A, B, C, and D) and follow a stepwise approach, beginning with a typical dose escalation in advanced solid tumors, followed by dose expansion in a range of indications. This design allows to gradually assess safety, preliminary efficacy, potential recommended Phase 2 dose (RP2D), and indications, while ensuring an acceptable benefit-risk balance along the way. Throughout this process, clinical data - including PK, biomarker, immunogenicity, safety, and efficacy, as well as non-clinical data, will be continuously collected and evaluated to support decision-making and ensure participant safety.

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A - BNT3212 monotherapy (dose escalation)

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.

Group Type: EXPERIMENTAL

BNT3212

Intervention Type: BIOLOGICAL

Intravenous infusion

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

Indication-specific cohort populations will be tested.

Group Type: EXPERIMENTAL

BNT3212

Intervention Type: BIOLOGICAL

Intravenous infusion

Part B - BNT3212 monotherapy DL2 (expansion cohort)

Indication-specific cohort populations will be tested.

Group Type: EXPERIMENTAL

BNT3212

Intervention Type: BIOLOGICAL

Intravenous infusion

Part B - BNT3212 monotherapy DL3 (expansion cohort)

Indication-specific cohort populations will be tested.

Group Type: EXPERIMENTAL

BNT3212

Intervention Type: BIOLOGICAL

Intravenous infusion

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

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.

Group Type: EXPERIMENTAL

BNT3212

Intervention Type: BIOLOGICAL

Intravenous infusion

BNT327

Intervention Type: BIOLOGICAL

Intravenous infusion

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

Indication-specific cohort populations will be tested.

Group Type: EXPERIMENTAL

BNT3212

Intervention Type: BIOLOGICAL

Intravenous infusion

BNT327

Intervention Type: BIOLOGICAL

Intravenous infusion

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

Indication-specific cohort populations will be tested.

Group Type: EXPERIMENTAL

BNT3212

Intervention Type: BIOLOGICAL

Intravenous infusion

BNT327

Intervention Type: BIOLOGICAL

Intravenous infusion

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

Indication-specific cohort populations will be tested.

Group Type: EXPERIMENTAL

BNT3212

Intervention Type: BIOLOGICAL

Intravenous infusion

BNT327

Intervention Type: BIOLOGICAL

Intravenous infusion

Interventions

BNT3212

Intravenous infusion

Intervention Type: BIOLOGICAL

BNT327

Intravenous infusion

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• For Parts C and D only: Have serious non-healing wounds, ulcer, or bone fracture.
• For Parts C and D only: Have evidence of major coagulation disorders or other significant risks of hemorrhage.
• For Parts C and D only: Have a history of serious Grade 3 or higher immune-related AEs that led to treatment discontinuation of a prior immunotherapy.
• For Parts C and D only: Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
• For Parts C and D only: Have received:

• anticoagulant therapy for therapeutic purposes (except low molecular weight heparin) within 14 days prior to the first dose of IMP.
• antiplatelet drugs within 10 days prior to the initiation of study treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biotheus (Hengqin) Co., Ltd.

UNKNOWN

Sponsor Role: collaborator

BioNTech (Shanghai) Pharmaceuticals Co., Ltd.

UNKNOWN

Sponsor Role: collaborator

BioNTech SE

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

BioNTech Responsible Person

Role: STUDY_DIRECTOR

BioNTech SE

Locations

Scientia Clinical Research Limited

Randwick, , Australia

Site Status: NOT_YET_RECRUITING

Shanghai East Hospital

Shanghai, , China

Site Status: RECRUITING

Countries

Australia; China

Central Contacts

: BioNTech clinical trials patient information

Role: CONTACT

patients@biontech.de

+49 6131 9084 ext. 0

Other Identifiers

BNT3212-01

Identifier Type: -

Identifier Source: org_study_id