First-in-human dose escalation and expansion of BNT3212 alone or with BNT327 for adults with advanced solid tumors

A Phase I/II, First-in-human, Open-label, Dose Escalation and Indication Expansion Study of the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of BNT3212 as Monotherapy or in Combination With BNT327 in Adults With Advanced Solid Tumors

This trial will test BNT3212 by itself and together with pumitamig (BNT327) in adults with advanced solid tumors who have exhausted standard treatment options.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 375 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: BioNTech SE (Industry-sponsored)
• Drugs / interventions: immunotherapy
• Locations: 16 sites (Adelaide and 15 other locations)
• Trial ID: NCT07147348 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, open-label, multi-site study using a stepwise four-part design to find safe and active dose(s) for BNT3212 alone and in combination with pumitamig (BNT327). Part A and C are dose-escalation cohorts (monotherapy and combination, respectively) and Parts B and D are dose-expansion cohorts across selected tumor indications. Key data collected will include safety, tolerability, pharmacokinetics, immunogenicity, biomarker profiles, and preliminary efficacy measures such as RECIST responses. Results will be used to identify a recommended dose for further testing while continuously monitoring participant safety.

Who should consider this trial

Good fit: Adults with histologically or cytologically confirmed locally advanced, recurrent, or metastatic solid tumors with at least one measurable lesion, ECOG performance status 0–1, adequate organ and cardiac function, life expectancy ≥3 months, and prior standard therapies exhausted or inappropriate are the intended participants.

Not a fit: Patients with poor performance status (ECOG ≥2), uncontrolled comorbidities, inadequate organ or cardiac function, very limited life expectancy, or who still have effective standard treatment options are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the regimen could provide a new treatment option that shrinks tumors or slows disease progression for patients with advanced solid tumors who have few other options.

How similar studies have performed: Combining immune checkpoint inhibition with anti-VEGF therapy has shown benefit in several cancers (for example atezolizumab plus bevacizumab), but PD-L1/VEGF-A bispecific antibodies are a novel approach with limited published first-in-human results so far.

Eligibility criteria

Key Inclusion Criteria:

* Participants with histologically or cytologically confirmed locally advanced, recurrent, or metastatic solid tumors that have received prior adequate therapy in accordance with local practice for their tumor type and stage of disease; 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.

Key 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 adverse events 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Where this trial is running

Adelaide and 15 other locations

• Cancer Research SA — Adelaide, Australia (Not_yet_recruiting)
• Monash Medical Centre — Clayton, Australia (Not_yet_recruiting)
• Peter MacCallum Cancer Centre — Melbourne, Australia (Not_yet_recruiting)
• The Alfred Hospital — Melbourne, Australia (Recruiting)
• One Clinical Research — Nedlands, Australia (Not_yet_recruiting)
• Scientia Clinical Research Limited — Randwick, Australia (Recruiting)
• Beijing Cancer Hospital — Beijing, China (Recruiting)
• Anhui Provincial Hospital — Hefei, China (Recruiting)
• First Affiliated Hospital of Xinxiang Medical University — Henan, China (Recruiting)
• Hunan Province Cancer Hospital — Hunan, China (Not_yet_recruiting)
• Shandong University-Jinan Central Hospital — Shandong, China (Not_yet_recruiting)
• Linyi Tumor Hospital — Shandong, China (Recruiting)
• Shanghai East Hospital — Shanghai, China (Recruiting)
• Shanghai GoBroad Cancer Hospital — Shanghai, China (Recruiting)
• Sichuan Cancer Hospital — Sichuan, China (Recruiting)
• Zhejiang Cancer Hospital — Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: : BioNTech clinical trials patient information

Conditions Advanced Solid Tumor; BNT3212; BNT327; Programmed death-ligand 1; Vascular endothelial growth factor A; Bispecific antibody; Antibody-drug conjugate; Combination with other investigational agents