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

Plain English Summary

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 is a Phase 2 clinical trial sponsored by BioNTech SE studying Advanced Solid Tumor. This study tests a new drug called BNT3212, alone or with another drug (BNT327), in adults with advanced solid tumors. It is for patients with advanced solid tumors who have not responded to or cannot tolerate standard treatments. Participation involves receiving the study drug intravenously, with regular check-ups and tests to monitor safety and effectiveness. Alternative treatments may include other chemotherapy, targeted therapies, or immunotherapy, depending on the specific cancer type and prior treatments. The trial aims to enroll 375 participants.

Official 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 pumitamig (also known as BNT327 or PM8002) as combination therapy, in adults with advanced solid tumors who have exhausted other treatment options.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with advanced solid tumors that have spread or returned after previous treatment. Patients must have tumors that can be measured and be in good general health (ECOG 0 or 1). Individuals with active infections, untreated brain metastases, or significant heart or lung problems may not be eligible. Specific criteria apply for certain tumor types and prior treatments, especially for combination therapy arms. This trial is studying Advanced Solid Tumor, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures will determine how safe the drug is, how the body processes it, and whether it shows early signs of shrinking tumors or stopping their growth. The specific primary outcome measures are: Parts A and C - Occurrence of dose limiting toxicities (DLTs) within a participant during the DLT observation period (Up to 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 (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 (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 (From the time of the first until last dose of IMP, approximately up to 31 months.); Parts B and D (expansion cohorts) - Objective response rate (ORR) (From first dose of IMP until end of study, approximately up to 31 months.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial is important because it explores a novel treatment approach for patients with advanced solid tumors who have limited options, aiming to fill a gap in current cancer therapies. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Advanced Solid Tumor, where improved treatment options are needed.

Investor Insight

This Phase I/II trial represents an early-stage investment in a novel cancer therapy, with potential for significant market impact if successful in treating a broad range of advanced solid tumors. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific goals of this trial for your type of cancer and what to expect regarding treatment schedule and potential side effects. Be prepared for regular clinic visits for drug infusions, blood tests, scans, and to report any new symptoms or side effects. Understand that this is an open-label study, meaning both you and your doctor will know which treatment you are receiving. This trial is currently recruiting participants. The trial is being conducted at 16 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 375 participants

Interventions

• BIOLOGICAL: BNT3212 — Intravenous infusion
• BIOLOGICAL: Pumitamig — Intravenous infusion

Primary Outcomes

• Parts A and C - Occurrence of dose limiting toxicities (DLTs) within a participant during the DLT observation period (Up to 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 (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 (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 (From the time of the first until last dose of IMP, approximately up to 31 months.)
• Parts B and D (expansion cohorts) - Objective response rate (ORR) (From first dose of IMP until end of study, approximately up to 31 months.)

Secondary Outcomes

• 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.)

Full 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.

Trial Locations

• Cancer Research SA, Adelaide, Australia
• Monash Medical Centre, Clayton, Australia
• Peter MacCallum Cancer Centre, Melbourne, Australia
• The Alfred Hospital, Melbourne, Australia
• One Clinical Research, Nedlands, Australia
• Scientia Clinical Research Limited, Randwick, Australia
• Beijing Cancer Hospital, Beijing, China
• Anhui Provincial Hospital, Hefei, China
• First Affiliated Hospital of Xinxiang Medical University, Henan, China
• Hunan Province Cancer Hospital, Hunan, China
• ...and 6 more locations

Frequently Asked Questions

Related Conditions

• Advanced Solid Tumors
• Metastatic Cancer
• Recurrent Cancer
• Cancer of Unknown Primary
• Carcinomas
• Sarcomas
• Melanoma
• Lung Cancer
• Colorectal Cancer
• Breast Cancer

More Advanced Solid Tumor Trials

View all Advanced Solid Tumor clinical trials