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

NCT ID: NCT07070232

Last Updated: 2026-01-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 980 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-12
• Study Completion Date: 2029-10-31

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.

Detailed Description

Both parts (Part 1 and Part 2) will start enrolling study participants independent of each other.

In Part 1, participants with histologically or cytologically confirmed advanced solid tumors will receive BNT326 monotherapy in the following cohorts:

• Cohort 1A: Cutaneous melanoma (second-line or higher treatment [2L+]).
• Cohort 1B: Actionable oncogenic alterations (AGA)-negative non-small cell lung cancer (NSCLC) 2L+.
• Cohort 1C: Epithelial growth factor receptor mutated (EGFRm) NSCLC 2L+.
• Cohort 1D: Rare melanoma (acral/uveal/mucosal melanoma) 2L+.
• Cohort 1E: Other advanced solid tumors 2L+.
• Cohort 1F (drug-drug interaction [DDI] Cohort): Advanced solid tumors.
• Cohort 1G: Cervical cancer 2L+.

In Part 2, BNT326 will be studied as monotherapy or in combination with other immunotherapeutic agents. The first combination treatment will be BNT326 with BNT327 (also known as pumitamig, BMS-986545, or PM8002). The following cohorts are planned:

• Cohort 2A: BNT326 + pumitamig for cutaneous melanoma 2L+.
• Cohort 2B: BNT326 + pumitamig for human epidermal growth factor receptor 2 (HER2)-negative breast cancer 2L+/first line treatment (1L).
• Cohort 2C (Optional): BNT326 + pumitamig for cutaneous melanoma first-line or higher treatment (1L+). This cohort may be added if BNT326 + pumitamig for cutaneous melanoma 2L+ is tolerated, and shows signs of efficacy.
• Cohort 2D: BNT326 + pumitamig for gastric cancer (GC)/gastroesophageal junction cancer (GEJC) 2L+.
• Cohort 2E: BNT326 + pumitamig for colorectal cancer 2L+.
• Cohort 2F: BNT326 + pumitamig for cervical cancer 2L+.

Participants in Cohorts 1A, 1B, and 1C (dose optimization cohorts) will be randomized to one of two dose levels (DLs) of BNT326 in a 1:1 ratio.

In the dose expansion of Cohorts 2A and 2B, participants will be randomized 1:1 to one of two DLs of BNT326 and pumitamig combination treatment.

During the randomized dose optimization and contribution of components of Cohorts 2D and 2E, participants will be randomized in a 1:1:1 ratio to one of three treatment arms (BNT326 DL2 or one of two DLs of BNT326 and pumitamig combination treatment).

No randomization is planned for Cohorts 1D, 1E, 1F, 1G, 2C and 2F.

The study will consist of a screening period, a treatment period, a safety follow-up period, an efficacy follow-up period, and a long-term survival follow-up period. Study treatment will be continued for up to 24 months or until disease progression, withdrawal of consent, termination of the study by the sponsor, or unacceptable toxicity. For each participant, the treatment and follow-up periods are projected to be completed within ~38 months (Part 1) and ~48 months (Part 2), unless participants are continuing to benefit from treatment per investigator's recommendation and upon sponsor approval.

Conditions

Advanced Solid Tumor

Study Design

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

Study Groups

Part 1 (Cohort 1A) - BNT326 monotherapy

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Part 1 (Cohort 1B) - BNT326 monotherapy

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Part 1 (Cohort 1C) - BNT326 monotherapy

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Part 1 (Cohort 1D) - BNT326 monotherapy

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Part 1 (Cohort 1E) - BNT326 monotherapy

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

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

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Itraconazole

Intervention Type: DRUG

Oral administration

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

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Paroxetine

Intervention Type: DRUG

Oral administration

Part 1 (Cohort 1G) - BNT326 monotherapy

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Part 2 (Cohort 2A) - BNT326 + pumitamig

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.

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Pumitamig

Intervention Type: DRUG

IV infusion

Part 2 (Cohort 2B) - BNT326 + pumitamig

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.

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Pumitamig

Intervention Type: DRUG

IV infusion

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

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Pumitamig

Intervention Type: DRUG

IV infusion

Part 2 (Cohort 2D1) - BNT326 monotherapy

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Part 2 (Cohort 2D2) - BNT326 + pumitamig

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Pumitamig

Intervention Type: DRUG

IV infusion

Part 2 (Cohort 2E1) - BNT326 monotherapy

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Part 2 (Cohort 2E2) - BNT326 + pumitamig

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Pumitamig

Intervention Type: DRUG

IV infusion

Part 2 (Cohort 2F) - BNT326 + pumitamig

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

Group Type: EXPERIMENTAL

BNT326

Intervention Type: DRUG

Intravenous (IV) infusion

Pumitamig

Intervention Type: DRUG

IV infusion

Interventions

BNT326

Intravenous (IV) infusion

Intervention Type: DRUG

Pumitamig

IV infusion

Intervention Type: DRUG

Itraconazole

Oral administration

Intervention Type: DRUG

Paroxetine

Oral administration

Intervention Type: DRUG

Other Intervention Names

BNT327; PM8002; BMS-986545

Eligibility Criteria

Inclusion Criteria

• 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:

• Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).
• Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR Tyrosine Kinase Inhibitors (TKI), with at least one being a third-generation EGFR TKI. If there is no third-generation EGFR TKI approved as part of SoC by local health authorities in a certain country, failure/progression on any EGFR TKI is acceptable for eligibility.
• Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.
• Prior chemotherapy and amivantamab are permitted only if administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease. Participants must not have received any other systemic therapies (such as chemotherapy, immunotherapy, or targeted agents) for advanced/metastatic disease, unless those treatments were given in combination with an EGFR TKI.
• Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
• Cohort 1D:

• Have histologically or cytologically confirmed diagnosis of unresectable or metastatic acral/uveal/mucosal melanoma not amenable to local therapy.
• Participants must have:

• Previously been treated with a PD-1 or PD-L1 inhibitor, if clinically indicated and available per local SoC, and/or
• For participants with Human Leukocyte Antigen Alleles (HLA-A)*02:01 serotype-positive disease (only applicable for uveal melanoma), previously been treated with tebentafusp-tebn if clinically indicated and available per local SoC, and
• Experienced progression during or after the previous treatment or discontinued from prior therapy due to intolerance.
• Cohorts 1E and 1F (DDI):

• Have histologically or cytologically confirmed diagnosis of unresectable or metastatic advanced solid tumor not amenable to ablative or curative approach including, but not limited to:

• Cholangiocarcinoma, including tumors of the intra- and extrahepatic biliary tract and gallbladder
• Hepatocellular carcinoma (HCC).
• Renal cell carcinoma
• Endometrial carcinoma, excluding those classified as true sarcomas
• Pancreatic ductal adenocarcinoma (PDAC) (see below other related inclusion criterion)
• Neuroendocrine tumor of pancreatic, gastrointestinal, lung, and thymus that is well differentiated, Grade 1 to 3.
• NSCLC (Cohort 1F only)
• Have experienced disease progression on at least one and no more than three lines of prior therapy or, for Cohort 1E only, discontinued from prior therapy due to intolerance.
• (For participants with PDAC only) Have received one or two lines of systemic therapy for metastatic tumors, and have experienced progression or intolerance to the treatment during or following therapy.
• Cohort 2A: Have histologically or cytologically confirmed diagnosis of unresectable or metastatic cutaneous melanoma not amenable to local therapy.
• Cohort 2B: Have histologically or cytologically confirmed diagnosis of recurrent unresectable or metastatic breast cancer that is documented as HER2-negative and either HR-negative or HR-positive per American Society of Clinical Oncology/College of American Pathologists guidelines.
• Cohort 2D:

• Histologically and/or cytologically documented metastatic adenocarcinoma and squamous carcinoma of GC/GEJC. (Note: ESCC is excluded).
• (2L subgroup): Had disease progression during or after one prior line of anti-cancer therapy for recurrent/metastatic disease.
• (3L subgroup): Has received two or more lines of prior anti-cancer therapy for recurrent/metastatic disease.
• (HER2-expression positive subgroup): Has received at least one prior line of systemic therapy for recurrent or metastatic disease, including a HER2-targeted agent in accordance with local SoC.
• Cohort 2E:

• Histologically and/or cytologically documented recurrent unresectable metastatic colorectal adenocarcinoma.
• Must have received at least one line to a maximum of three lines of prior SoC treatment for recurrent/metastatic disease.
• Cohort 1G and 2F:

• Histologically and/or cytologically documented recurrent unresectable metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology.
• Must have received platinum-based chemotherapy, with or without an anti-PD-(L)1 agent and bevacizumab for metastatic/recurrent disease, unless the patient is not a candidate in the opinion of the treating physician.

Exclusion Criteria

• 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.
• Are subject to exclusion periods from another investigational study.
• Specific to BNT327: Participants with significant risks of hemorrhage or evidence of major coagulation disorders as specified in the protocol.
• Specific to BNT327: Have a history of intolerance to treatment with an anti-VEFG, anti-PD-1/PDL-1, or similar substance, including, but not limited to, bevacizumab, ramucirumab, atezolizumab, pembrolizumab, nivolumab, or other related therapies.
• Cohort 1E: Have histological diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.

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

Sponsors

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

Hartford Healthcare

Hartford, Connecticut, United States

Site Status: NOT_YET_RECRUITING

Yale University

New Haven, Connecticut, United States

Site Status: RECRUITING

Florida Cancer Specialists

Sarasota, Florida, United States

Site Status: RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status: NOT_YET_RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

START Midwest, LLC

Grand Rapids, Michigan, United States

Site Status: RECRUITING

Memorial Sloan Kettering Hospital

New York, New York, United States

Site Status: RECRUITING

Duke Cancer Institute

Durham, North Carolina, United States

Site Status: NOT_YET_RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

South Texas Accelerated Research Therapeutics (START), LLC

San Antonio, Texas, United States

Site Status: RECRUITING

START Mountain Region

West Valley City, Utah, United States

Site Status: RECRUITING

The Board of Regents of the University of Wisconsin

Madison, Wisconsin, United States

Site Status: NOT_YET_RECRUITING

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Site Status: NOT_YET_RECRUITING

Melanoma Institute Australia

Wollstonecraft, New South Wales, Australia

Site Status: RECRUITING

Tasman Oncology Research Ltd

Southport, Queensland, Australia

Site Status: RECRUITING

Cancer Research SA

Adelaide, South Australia, Australia

Site Status: RECRUITING

Austin Health

Heidelberg, Victoria, Australia

Site Status: RECRUITING

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status: NOT_YET_RECRUITING

One Clinical Research Pty Ltd

Nedlands, Western Australia, Australia

Site Status: RECRUITING

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status: RECRUITING

Ziekenhuis Aan de Stroom ZAS vzw

Wilrijk, , Belgium

Site Status: RECRUITING

Istituto Nazionale Tumori Fondazione G. Pascale

Naples, , Italy

Site Status: RECRUITING

Hospital Beata Maria Ana

Madrid, , Spain

Site Status: RECRUITING

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Site Status: RECRUITING

Centro Integral Oncologico Clara Campal

Madrid, , Spain

Site Status: RECRUITING

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, , Spain

Site Status: RECRUITING

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Site Status: RECRUITING

Velindre Cancer Centre

Cardiff, , United Kingdom

Site Status: RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status: RECRUITING

The Clatterbridge Cancer Centre

Liverpool, , United Kingdom

Site Status: NOT_YET_RECRUITING

Royal Free Hospital

London, , United Kingdom

Site Status: RECRUITING

Royal Marsden Hospital-London

London, , United Kingdom

Site Status: RECRUITING

Imperial College London

London, , United Kingdom

Site Status: RECRUITING

University College London Hospitals

London, , United Kingdom

Site Status: RECRUITING

The Christie Hospital

Manchester, , United Kingdom

Site Status: RECRUITING

Northern Centre for Cancer Care

Newcastle upon Tyne, , United Kingdom

Site Status: RECRUITING

Southampton General Hospital

Southampton, , United Kingdom

Site Status: RECRUITING

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status: RECRUITING

Countries

United States; Australia; Belgium; Italy; Spain; United Kingdom

Central Contacts

BioNTech clinical trials patient information

Role: CONTACT

patients@biontech.de

+49 6131 9084 ext. 0

Other Identifiers

2024-517261-16-00

Identifier Type: CTIS

Identifier Source: secondary_id

1011236

Identifier Type: OTHER

Identifier Source: secondary_id

BNT326-01

Identifier Type: -

Identifier Source: org_study_id