A Clinical Study to Test if an Investigational Treatment Called BNT326 is Safe and Potentially Beneficial When Used Alone or in Combination With Other Investigational Treatments Such as BNT327, for People With Advanced Malignant Tumors

NCT07070232 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: BNT326-012024-517261-16-001011236
• Study Type: interventional
• Target: 980
• Locations: 8 countries
• Sites: 64

Brief Summary

This study will evaluate the safety, efficacy, optimal dose, and pharmacokinetics (PK) of BNT326 as monotherapy (Part 1) and as combination treatment with immunotherapeutic agents (Part 2) in participants with histologically or cytologically confirmed solid tumors that are advanced (i.e., either metastatic or recurrent tumors with no further definitive treatment possible) and/or have relapsed/progressed after prior therapy.

Conditions

Advanced Solid Tumor

Keywords

Combination with other investigational agents; Programmed death-ligand 1 (PD-L1); Antibody-drug conjugate (ADC); Human epidermal growth factor receptor 3 (HER3); Programmed Death-1 (PD-1); Programmed Death-1 monoclonal antibodies; Combination chemotherapy; Anti vascular endothelial growth factor-A (anti-VEGF-A); Bispecific antibody; Immunotherapy; Dose optimization; Time to progression; Vascular endothelial growth factor (VEGF); Cutaneous Melanoma; Rare melanoma; Actionable oncogenic alterations (AGA)-negative non-small cell lung cancer (NSCLC); Epithelial growth factor receptor mutated (EGFRm) NSCLC; Gastric cancer (GC); Gastroesophageal junction cancer (GEJC)

Outcome Measures

Primary Outcomes (6)

• Parts 1 and 2 - All cohorts except Cohort 1F - Occurrence of treatment emergent adverse events (TEAEs), treatment related adverse events (TRAEs), treatment emergent serious adverse events (TESAEs), and treatment related serious adverse events (TRSAEs)

  By cohort and by dose in (Part 1), and by cohort and combination treatment regimen (in Part 2).

  from first dose of investigational medicinal product (IMP) up to 42 days (Part 1) and 90 days (Part 2) after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to 26 months Part 1 or 27 months Part 2)

• Parts 1 and 2 - All cohorts except Cohort 1F - Occurrence of dose interruption, reduction, and treatment discontinuations due to TEAEs

  By cohort and by dose in (Part 1), and by cohort and combination treatment regimen (in Part 2)

  from first dose of IMP up to 42 days (Part 1) and 90 days (Part 2) after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to 26 months Part 1 or 27 months Part 2)

• Parts 1 and 2 - All cohorts except Cohort 1F - Confirmed overall response rate (ORR)

  Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) based on the investigator's assessment (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]) is observed as best overall response. By cohort and by dose in (Part 1), and by cohort and combination treatment regimen (in Part 2).

  from the time of initiation of the first dose of IMP up to approximately 38 months (Part 1) and approximately 48 months (Part 2)

• Part 2 - Occurrence of dose limiting toxicities (DLTs)

  During the DLT observation period.

  from the time of initiation of the first dose of IMP up to 21 days

• Part 1 - Cohort 1F (DDI) only - PK assessment: Maximum concentration (Cmax) derived from serum concentrations of BNT326 ADC and unconjugated payload

  Evaluation of Cmax without and in combination with the CYP inhibitors (± itraconazole or ± paroxetine). Treatment comparison using geometric mean ratio of Cycle 3 as compared with Cycle 2 as a reference.

  from the time of initiation of the first dose of IMP up to safety follow-up visit, approximately 42 days post last IMP dose

• Part 1 - Cohort 1F (DDI) only - PK assessment: Area under the curve (AUC) over the last 17-day dosing interval derived from serum concentrations of BNT326 ADC and unconjugated payload

  Evaluation of AUC over the last 17-day dosing interval without and in combination with the CYP inhibitors (± itraconazole or ± paroxetine). Treatment comparison using geometric mean ratio of Cycle 3 as compared with Cycle 2 as a reference.

  from the time of initiation of the first dose of IMP up to safety follow-up visit, approximately 42 days post last IMP dose

Secondary Outcomes (17)

• Part 1 - Cohort 1F (DDI) only - Occurrence of TEAEs, TRAEs, TESAEs, and TRSAEs

  from the time of initiation of the first dose of IMP to 42 days after the last dose of IMP

• Part 1 - Cohort 1F (DDI) only - Occurrence of dose interruption, reduction, and treatment discontinuations due to TEAEs

  from the time of initiation of the first dose of IMP to 42 days after the last dose of IMP

• Part 1 - Cohort 1F (DDI) only - Occurrence of clinically relevant changes from baseline for vital signs

  from the time of initiation of the first dose of IMP to 42 days after the last dose of IMP

• Part 1 - Cohort 1F (DDI) only - Occurrence of clinically relevant changes from baseline for clinical laboratory tests

  from the time of initiation of the first dose of IMP to 42 days after the last dose of IMP

• Part 1 - Cohort 1F (DDI) only - Occurrence of clinically relevant changes from baseline for cardiac function

  from the time of initiation of the first dose of IMP to 42 days after the last dose of IMP

Study Arms (16)

Part 1 (Cohort 1A) - BNT326 monotherapy

EXPERIMENTAL

BNT326 (DL1 or DL2) in participants with cutaneous melanoma 2L+

Drug: BNT326

Part 1 (Cohort 1B) - BNT326 monotherapy

EXPERIMENTAL

BNT326 (DL1 or DL2) in participants with NSCLC 2L+ AGA-negative

Drug: BNT326

Part 1 (Cohort 1C) - BNT326 monotherapy

EXPERIMENTAL

BNT326 (DL1 or DL2) in participants with NSCLC 2L+ EGFRm

Drug: BNT326

Part 1 (Cohort 1D) - BNT326 monotherapy

EXPERIMENTAL

BNT326 (DL2) in participants with rare melanoma 2L+

Drug: BNT326

Part 1 (Cohort 1E) - BNT326 monotherapy

EXPERIMENTAL

BNT326 (DL2) in participants with advanced solid tumors 2L+

Drug: BNT326

Part 1 (Cohort 1F, DDI) - BNT326 + itraconazole

EXPERIMENTAL

BNT326 (DL1 or DL2) + itraconazole in participants with advanced solid tumors

Drug: BNT326; Drug: Itraconazole

Part 1 (Cohort 1F, DDI) - BNT326 + paroxetine

EXPERIMENTAL

BNT326 (DL1 or DL2) + paroxetine in participants with advanced solid tumors

Drug: BNT326; Drug: Paroxetine

Part 1 (Cohort 1G) - BNT326 monotherapy

EXPERIMENTAL

BNT326 (DL2) in participants with cervical cancer 2L+

Drug: BNT326

Part 2 (Cohort 2A) - BNT326 + pumitamig

EXPERIMENTAL

Combination therapy of BNT326 (DL1 or DL2) + pumitamig (DL1 or DL2) in participants with cutaneous melanoma 2L+. Optionally, combinations with lower doses of BNT326 and/or pumitamig may be explored.

Drug: BNT326; Drug: Pumitamig

Part 2 (Cohort 2B) - BNT326 + pumitamig

EXPERIMENTAL

Combination therapy of BNT326 (DL1 or DL2) + pumitamig (DL1 or DL2) in participants with HER2-negative breast cancer (triple-negative breast cancer and hormone receptor positive \[HR+\]/HER2- breast cancer) 2L+/1L.

Drug: BNT326; Drug: Pumitamig

Part 2 (Cohort 2C) - Optional - BNT326 + pumitamig

EXPERIMENTAL

Combination therapy of BNT326 (DL1 or DL2) + pumitamig (DL1) in participants with cutaneous melanoma 1L+

Drug: BNT326; Drug: Pumitamig

Part 2 (Cohort 2D1) - BNT326 monotherapy

EXPERIMENTAL

BNT326 (DL2) in participants with GC/GEJC 2L+

Drug: BNT326

Part 2 (Cohort 2D2) - BNT326 + pumitamig

EXPERIMENTAL

Combination therapy of BNT326 (DL2) + pumitamig (DL1 or DL2) in participants with GC/GEJC 2L+

Drug: BNT326; Drug: Pumitamig

Part 2 (Cohort 2E1) - BNT326 monotherapy

EXPERIMENTAL

BNT326 (DL2) in participants with colorectal cancer 2L+

Drug: BNT326

Part 2 (Cohort 2E2) - BNT326 + pumitamig

EXPERIMENTAL

Combination therapy of BNT326 (DL2) + pumitamig (DL1 or DL2) in participants with colorectal cancer 2L+

Drug: BNT326; Drug: Pumitamig

Part 2 (Cohort 2F) - BNT326 + pumitamig

EXPERIMENTAL

Combination therapy of BNT326 (DL2) + pumitamig (DL2) in participants with cervical cancer 2L+

Drug: BNT326; Drug: Pumitamig

Interventions

BNT326 DRUG

Intravenous (IV) infusion

Part 1 (Cohort 1A) - BNT326 monotherapy; Part 1 (Cohort 1B) - BNT326 monotherapy; Part 1 (Cohort 1C) - BNT326 monotherapy; Part 1 (Cohort 1D) - BNT326 monotherapy; Part 1 (Cohort 1E) - BNT326 monotherapy; Part 1 (Cohort 1F, DDI) - BNT326 + itraconazole; Part 1 (Cohort 1F, DDI) - BNT326 + paroxetine; Part 1 (Cohort 1G) - BNT326 monotherapy; Part 2 (Cohort 2A) - BNT326 + pumitamig; Part 2 (Cohort 2B) - BNT326 + pumitamig; Part 2 (Cohort 2C) - Optional - BNT326 + pumitamig; Part 2 (Cohort 2D1) - BNT326 monotherapy; Part 2 (Cohort 2D2) - BNT326 + pumitamig; Part 2 (Cohort 2E1) - BNT326 monotherapy; Part 2 (Cohort 2E2) - BNT326 + pumitamig; Part 2 (Cohort 2F) - BNT326 + pumitamig

Pumitamig DRUG

IV infusion

Also known as: BNT327, PM8002, BMS-986545

Part 2 (Cohort 2A) - BNT326 + pumitamig; Part 2 (Cohort 2B) - BNT326 + pumitamig; Part 2 (Cohort 2C) - Optional - BNT326 + pumitamig; Part 2 (Cohort 2D2) - BNT326 + pumitamig; Part 2 (Cohort 2E2) - BNT326 + pumitamig; Part 2 (Cohort 2F) - BNT326 + pumitamig

Itraconazole DRUG

Oral administration

Part 1 (Cohort 1F, DDI) - BNT326 + itraconazole

Paroxetine DRUG

Oral administration

Part 1 (Cohort 1F, DDI) - BNT326 + paroxetine

Eligibility Criteria

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

You may qualify if:

• Aged ≥18 years at the time of giving informed consent. Local laws will be followed if the age of consent is older.
• Have histologic or cytologic documented advanced disease, either at relapse or upon diagnosis of metastatic disease. This requirement may be considered met when advanced disease derives from unequivocal progression of a previously biopsied site of disease (e.g., progression of residual tumor after concomitant chemo-radiation for Stage III NSCLC).
• Have measurable disease defined by RECIST v1.1.
• All participants must provide a tumor tissue sample (Formalin-fixed paraffin-embedded \[FFPE\] slides) from archival tissue. The archival tissue can be an FFPE block or freshly cut slides derived from the advanced setting or a new/fresh tumor biopsy.
• Have ECOG performance status of 0 or 1.
• Have adequate organ and bone marrow function (as specified in the protocol) within 7 days before randomization/enrollment.
• Cohort 1A:
• Have histologically or cytologically confirmed diagnosis of unresectable or metastatic cutaneous melanoma not amenable to local therapy.
• Participants must have previously received a PD-1 or PD-L1 inhibitor, and, for participants with human gene that encodes a protein called B-Raf (BRAF) gene mutant melanoma, a prior treatment regimen that included vemurafenib, dabrafenib, or another BRAF gene inhibitor with or without mitogen-activated protein kinase protein inhibitor, if available and clinically indicated per local standard of care (SoC) and have experienced progression during or after the previous treatment or discontinued from prior therapy due to intolerance.
• Cohort 1B and 1C: Have advanced (i.e., metastatic or locally recurrent where local therapy with curative intent is not possible) non-squamous or squamous NSCLC.
• Cohort 1B:
• Have no actionable genomic alterations, such as EGFR mutations, anaplastic lymphoma kinase rearrangements, or other genomic alterations for which targeted molecular therapies are available. For enrolled participants with predominantly squamous histology tumors, molecular testing will not be required in cases where it is not part of the SoC.
• Have experienced relapse or progression during or after treatment with standard systemic therapy including platinum-based chemotherapy and/or immune checkpoint inhibitor in the advanced/metastatic setting or discontinued from prior therapy due to intolerance.
• Participants must have received 1 to 3 lines of systemic treatment, which can include anti-PD-1/PD-L1 therapy (if PD-L1 positive), chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. Prior chemotherapy must be limited to 2 lines or less.
• Cohort 1C:

You may not qualify if:

• Have a history of intolerance to treatment with a topoisomerase I inhibitor or intolerance to an ADC that consists of a topoisomerase I inhibitor, including but not limited to topotecan, irinotecan, and deruxtecan (e.g., severe diarrhea).
• Have an uncontrolled concomitant or intercurrent illness that contra-indicates study participation, limits compliance with study procedures or substantially increases the risk of incurring adverse events, including:
• Bleeding diathesis or active hemorrhage,
• Active infection,
• Child-Pugh class B or C cirrhosis,
• Pulmonary disease with significant impact in lung function
• Oncologic emergencies or complications (e.g., malignant hypercalcemia, superior vena cava syndrome, carcinoid syndrome that is unstable and with available alternative therapies),
• Psychiatric or abuse condition
• Infectious colitis Grade ≥2 not resolved to Grade 1 within 72 hours within the past 3 months.
• Have LVEF \<50% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.
• Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
• Have a history of (non-infectious) interstitial lung disease (ILD) /pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable.
• Are a participant of child-bearing potential who are pregnant or breastfeeding or are planning pregnancy within 225 days (\~7.5 months) after receiving last dose of BNT326 and within 6 months after last dose of BNT327, whichever is longer.
• Are potentially fertile males, who are planning to father children during the study or within 135 days (\~4.5 months) after the last dose of BNT326 and within 6 months after last dose of BNT327, whichever is longer.
• Specific to BNT327: Participants with significant risks of hemorrhage or evidence of major coagulation disorders as specified in the protocol.

Sponsors & Collaborators

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

Study Sites (64)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

NOT YET RECRUITING

University of California San Francisco

San Francisco, California, 94158, United States

NOT YET RECRUITING

Hartford Healthcare

Hartford, Connecticut, 06102, United States

RECRUITING

Yale University

New Haven, Connecticut, 06511, United States

RECRUITING

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612-9497, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

Brigitte Harris Cancer Pavilion BHCP

Detroit, Michigan, 48202, United States

NOT YET RECRUITING

START Midwest, LLC

Grand Rapids, Michigan, 49546, United States

RECRUITING

Memorial Sloan Kettering Hospital

New York, New York, 10065, United States

RECRUITING

Duke Cancer Institute

Durham, North Carolina, 27710, United States

NOT YET RECRUITING

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

South Texas Accelerated Research Therapeutics (START), LLC

San Antonio, Texas, 78229, United States

RECRUITING

START Mountain Region

West Valley City, Utah, 84119, United States

RECRUITING

The Board of Regents of the University of Wisconsin

Madison, Wisconsin, 53792-6188, United States

RECRUITING

Blacktown Hospital

Blacktown, New South Wales, 2148, Australia

RECRUITING

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

RECRUITING

Tasman Oncology Research Ltd

Southport, Queensland, 4215, Australia

RECRUITING

Cancer Research SA

Adelaide, South Australia, 5000, Australia

RECRUITING

Austin Health

Heidelberg, Victoria, 3084, Australia

RECRUITING

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

RECRUITING

One Clinical Research Pty Ltd

Nedlands, Western Australia, 6009, Australia

RECRUITING

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

RECRUITING

Centre hospitalier universitaire de Liège

Liège, 4000, Belgium

RECRUITING

Ziekenhuis Aan de Stroom ZAS vzw

Wilrijk, 2610, Belgium

RECRUITING

Charité - Campus Charité Mitte

Berlin, 10117, Germany

NOT YET RECRUITING

Universitaetsklinikum Essen

Essen, 45147, Germany

RECRUITING

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

RECRUITING

Klinikum der Universität München Campus Grosshadern

München, 81377, Germany

NOT YET RECRUITING

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

RECRUITING

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori

Meldola, 47014, Italy

NOT YET RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

IEO Istituto Europeo di Oncologia

Milan, 20141, Italy

RECRUITING

Istituto Nazionale Tumori Fondazione G. Pascale

Naples, 80131, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

Istituto Clinico Humanitas

Rozzano, 20089, Italy

RECRUITING

Hospital Universitari Vall d'Hebron - VHIO

Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

NOT YET RECRUITING

START Barcelona -HM Nou Delfos

Barcelona, 8023, Spain

RECRUITING

Hospital de San Pedro

Logroño, 26006, Spain

NOT YET RECRUITING

Hospital Beata Maria Ana

Madrid, 28007, Spain

RECRUITING

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

RECRUITING

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, 28223, Spain

RECRUITING

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

RECRUITING

Dr. Abdurrahman Yurtaslan Ankara Oncology Traning & Research

Ankara, 6200, Turkey (Türkiye)

NOT YET RECRUITING

Hacettepe Oncology Hospital

Ankara, 6230, Turkey (Türkiye)

NOT YET RECRUITING

Yeditepe University Kosuyolu Hospital

Istanbul, 34718, Turkey (Türkiye)

NOT YET RECRUITING

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

RECRUITING

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

RECRUITING

The Clatterbridge Cancer Centre

Liverpool, L7 8YA, United Kingdom

RECRUITING

Royal Free Hospital

London, NW3 2QG, United Kingdom

RECRUITING

Royal Marsden Hospital-London

London, SW3 6JJ, United Kingdom

RECRUITING

Imperial College London

London, W12 0HS, United Kingdom

RECRUITING

University College London Hospitals

London, W1T 7HA, United Kingdom

RECRUITING

The Christie Hospital

Manchester, M20 4BX, United Kingdom

RECRUITING

Northern Centre for Cancer Care

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

RECRUITING

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Lethal Congenital Contracture Syndrome 2; Melanoma; Carcinoma, Non-Small-Cell Lung; Stomach Neoplasms

Interventions

Itraconazole; Paroxetine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Piperidines

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2025
• First Posted: July 17, 2025
• Study Start: August 12, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): October 1, 2029
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (9); GB (12); US (18); IT (6); BE (3); AU (8); DE (5); TU (3)