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
Status and phase
Conditions
Treatments
Details and patient eligibility
About
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.
Full 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.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Key Inclusion Criteria:
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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.
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Have at least one measurable lesion based on RECIST v1.1.
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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).
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Predicted life expectancy of ≥3 months.
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Left ventricular ejection fraction ≥50% by either echocardiography or multigated acquisition scan within 28 days prior to first dose of study treatment.
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Adequate liver, renal, hematological, and coagulation function.
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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.
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The investigator considers discontinuation of protocol-defined anti-cancer therapies and restricted medications with protocol-defined washout periods as medically acceptable.
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For Parts B and D only: Participants must be diagnosed with specific indications.
Key Exclusion Criteria:
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Active infection (e.g., bacterial or fungal infections) requiring systemic treatment (e.g., severe pneumonia, bacteremia, sepsis), except oral antibiotics.
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Participants with primary central nervous system (CNS) malignancies.
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Active CNS metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
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Unstable pleural effusion or ascites requiring thoracentesis or paracentesis within 14 days prior to initiation of study treatment.
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Have active, or a history of, pneumonitis requiring treatment with steroids, or has active, or a history of, interstitial lung disease.
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Clinically significant pulmonary complications.
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History of severe cardiovascular disease.
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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.
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Have active or chronic corneal disorders or with any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.
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Have uncontrolled hypertension while on antihypertensive medicine or poorly controlled diabetes.
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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.
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Unstable thrombotic event (e.g., deep vein thrombosis, arterial thrombosis, pulmonary embolism).
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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.
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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).
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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.
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For Parts C and D only: Have serious non-healing wounds, ulcer, or bone fracture.
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For Parts C and D only: Have evidence of major coagulation disorders or other significant risks of hemorrhage.
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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.
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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.
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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.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial design
Primary purpose
Allocation
Interventional model
Masking
375 participants in 8 patient groups
Trial contacts and locations
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Central trial contact
: BioNTech clinical trials patient information
Data sourced from clinicaltrials.gov
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