Recruiting

Phase 1

Phase 2

BNT326, ImmunotherapeuticsA 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

Sponsor:

BioNTech SE

Code:

NCT07070232

Conditions

Advanced Solid Tumor

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

BNT326

Pumitamig

Itraconazole

Paroxetine

Study Details

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

Study ID

NCT07070232

Start date

Aug 12, 2025

Status verified date

Sep, 2026

Completion date

Mar, 2030

Anticipated

Primary completion date

Mar, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):

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.
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 in the metastatic setting, 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: Esophageal squamous-cell carcinoma 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.

Key Exclusion Criteria (applicable to all participants and all parts unless otherwise specified):

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,
Known 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 pumitamig, 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 pumitamig, whichever is longer.
Are subject to exclusion periods from another investigational study.
Specific to pumitamig: Participants with significant risks of hemorrhage or evidence of major coagulation disorders as specified in the protocol.
Specific to pumitamig: Have a history of intolerance to treatment with an anti-vascular endothelial growth factor, 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Study Design

Enrollment

1438 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1 (Cohort 1A) - BNT326 monotherapy

BNT326 (DL1 or DL2 or DL3) in participants with cutaneous melanoma 2L+

experimental: Part 1 (Cohort 1B) - BNT326 monotherapy

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

experimental: Part 1 (Cohort 1C) - BNT326 monotherapy

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

experimental: Part 1 (Cohort 1D) - BNT326 monotherapy

BNT326 (DL2 or DL3) in participants with rare melanoma 2L+

experimental: Part 1 (Cohort 1E) - BNT326 monotherapy

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

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

BNT326 (DL1 or DL2 or DL3) + itraconazole in participants with advanced solid tumors

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

BNT326 (DL1 or DL2 or DL3) + paroxetine in participants with advanced solid tumors

experimental: Part 1 (Cohort 1G) - BNT326 monotherapy

BNT326 (DL2 or DL3) in participants with cervical cancer 2L+

experimental: Part 2 (Cohort 2A dose escalation) - BNT326 + pumitamig

Combination therapy of BNT326 (DL1 or DL2 or DL3) + pumitamig (DL1 or DL2) in participants with cutaneous melanoma 2L+. Optionally, combinations with lower doses of BNT326 and/or pumitamig may be explored.

experimental: Part 2 (Cohort 2A dose randomization/expansion) - BNT326 + pumitamig

Combination therapy of BNT326 (DL1 or DL2 or DL3) + pumitamig (DL3 or DL4 or DL 5) in participants with cutaneous melanoma 2L+. Optionally, combinations with lower doses of BNT326 and/or pumitamig may be explored.

experimental: Part 2 (Cohort 2B dose escalation) - BNT326 + pumitamig

Combination therapy of BNT326 (DL1 or DL2 or DL3) + pumitamig (DL1 or DL2) in participants with HER2-negative breast cancer (triple-negative breast cancer and hormone receptor-positive /HER2-negative breast cancer) 2L+/1L

experimental: Part 2 (Cohort 2B dose randomization/expansion) - BNT326 + pumitamig

Combination therapy of BNT326 (DL1 or DL2 or DL3) + pumitamig (DL3 or DL4 or DL 5) in participants with HER2-negative breast cancer (triple-negative breast cancer and hormone receptor-positive /HER2-negative breast cancer) 2L+/1L

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

Combination therapy of BNT326 + pumitamig in participants with cutaneous melanoma 1L+

experimental: Part 2 (Cohort 2D1) - BNT326 monotherapy

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

experimental: Part 2 (Cohort 2D2) - BNT326 + pumitamig

Combination therapy of BNT326 (DL2 or DL3) + pumitamig (DL1 or DL2) in participants with GC/GEJC 2L+

experimental: Part 2 (Cohort 2E1) - BNT326 monotherapy

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

experimental: Part 2 (Cohort 2E2) - BNT326 + pumitamig

Combination therapy of BNT326 (DL2 or DL3) + pumitamig (DL1 or DL2) in participants with colorectal cancer 2L+

experimental: Part 2 (Cohort 2F) - BNT326 + pumitamig

Combination therapy of BNT326 with pumitamig in participants with cervical cancer 2L+ (BNT326 DL2 with pumitamig DL1 or DL2 or BNT326 DL3 with pumitamig DL1 or DL2)

Interventions

BNT326

Intravenous (IV) infusion

Pumitamig

IV infusion

Itraconazole

Oral administration

Paroxetine

Oral administration

Primary outcome measure

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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: from the time of initiation of the first dose of IMP up to safety follow-up visit, approximately 42 days post last IMP dose ]

Central Contacts and Locations

Central contacts

BioNTech clinical trials patient information

+49 6131 9084 patients@biontech.de

Locations

Hartford Healthcare

Recruiting

Hartford, Connecticut, United States, 06102

Yale University

Recruiting

New Haven, Connecticut, United States, 06511

Florida Cancer Specialists

Recruiting

Sarasota, Florida, United States, 34232

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612-9497

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02215

Brigitte Harris Cancer Pavilion BHCP

Recruiting

Detroit, Michigan, United States, 48202

START Midwest, LLC

Recruiting

Grand Rapids, Michigan, United States, 49546

Memorial Sloan Kettering Hospital

Recruiting

New York, New York, United States, 10065

Cleveland Clinic Taussig Cancer Center

Recruiting

Cleveland, Ohio, United States, 44195

University of Pittsburgh Medical Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

South Texas Accelerated Research Therapeutics (START), LLC

Recruiting

San Antonio, Texas, United States, 78229

START Mountain Region

Recruiting

West Valley City, Utah, United States, 84119

The Board of Regents of the University of Wisconsin

Recruiting

Madison, Wisconsin, United States, 53792-6188

More Information

Sponsor

BioNTech SE

Last update posted

Sep 2, 2026

Last verified

Sep, 2026

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)
Gastric cancer (GC)
Gastroesophageal junction cancer (GEJC)
Epidermal growth factor receptor mutated (EGFRm) NSCLC

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by BioNTech SE on 2026-09-02.