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
Start Date
8/12/2025
Completion Date
3/1/2030
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: Epidermal 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 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. An additional, non-randomized dose level arm (DL3) is included in Cohort 1A. During the dose randomization phase of Cohorts 2A and 2B, participants will be randomized 1:1 to one of two combination DLs. 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 monotherapy at DL2 or BNT326 DL2 with pumitamig \[DL1 or DL2\] combination treatment). An additional, non-randomized dose level arm is included in Cohorts 2D and 2E (BNT326 DL3 in combination with pumitamig DL1 or DL2). 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. If a participant continues to derive clinical benefit at the end of study, study treatment continuation can be considered case-by-case after discussion with the sponsor's medical monitor. 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.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
BNT326
Pumitamig
Itraconazole
Paroxetine
Conditions
Locations
Mayo Clinic Arizona
Phoenix, Arizona 85054
United States
University of California San Francisco
San Francisco, California 94158
United States
Hartford Healthcare
Hartford, Connecticut 06102
United States
Yale University
New Haven, Connecticut 06511
United States
Florida Cancer Specialists
Sarasota, Florida 34232
United States
Moffitt Cancer Center
Tampa, Florida 33612-9497
United States
Dana Farber Cancer Institute
Boston, Massachusetts 02215
United States
Massachusetts General Hospital
Boston, Massachusetts 02215
United States
Brigitte Harris Cancer Pavilion BHCP
Detroit, Michigan 48202
United States
START Midwest, LLC
Grand Rapids, Michigan 49546
United States
Memorial Sloan Kettering Hospital
New York, New York 10065
United States
Duke Cancer Institute
Durham, North Carolina 27710
United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio 44195
United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania 15232
United States
The University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United States
South Texas Accelerated Research Therapeutics (START), LLC
San Antonio, Texas 78229
United States
START Mountain Region
West Valley City, Utah 84119
United States
The Board of Regents of the University of Wisconsin
Madison, Wisconsin 53792-6188
United States
Blacktown Hospital
Blacktown, New South Wales 2148
Australia
St Vincent's Hospital Sydney
Darlinghurst, New South Wales 2010
Australia
Melanoma Institute Australia
Wollstonecraft, New South Wales 2065
Australia
Tasman Oncology Research Ltd
Southport, Queensland 4215
Australia
Cancer Research SA
Adelaide, South Australia 5000
Australia
Peninsula and South Eastern Haematology & Oncology Group
Frankston, Victoria 3199
Australia
Austin Health
Heidelberg, Victoria 3084
Australia
The Alfred Hospital
Melbourne, Victoria 3004
Australia
One Clinical Research Pty Ltd
Nedlands, Western Australia 6009
Australia
Universitair Ziekenhuis Gent
Ghent, 9000
Belgium
Centre hospitalier universitaire de Liège
Liège, 4000
Belgium
Ziekenhuis Aan de Stroom ZAS vzw
Wilrijk, 2610
Belgium
Charité - Campus Charité Mitte
Berlin, 10117
Germany
Universitaetsklinikum Essen
Essen, 45147
Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55131
Germany
Klinikum der Universität München Campus Grosshadern
München, 81377
Germany
Universitätsklinikum Tübingen
Tübingen, 72076
Germany
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
Meldola, 47014
Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
Italy
IEO Istituto Europeo di Oncologia
Milan, 20141
Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Naples, 80131
Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, 00168
Italy
Istituto Clinico Humanitas
Rozzano, 20089
Italy
Hospital Universitari Vall d'Hebron - VHIO
Barcelona, 08035
Spain
Hospital Clinic de Barcelona
Barcelona, 08036
Spain
START Barcelona -HM Nou Delfos
Barcelona, 8023
Spain
Hospital de San Pedro
Logroño, 26006
Spain
Hospital Beata Maria Ana
Madrid, 28007
Spain
Hospital Clinico San Carlos
Madrid, 28040
Spain
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
Spain
Centro Integral Oncologico Clara Campal
Madrid, 28050
Spain
Hospital Universitario Quironsalud Madrid
Pozuelo de Alarcón, 28223
Spain
Hospital Universitari i Politecnic La Fe
Valencia, 46026
Spain
Dr. Abdurrahman Yurtaslan Ankara Oncology Traning & Research
Ankara, 06200
Turkey (Türkiye)
Hacettepe Oncology Hospital
Ankara, 6230
Turkey (Türkiye)
Ankara Bilkent City Hospital Phase 1 Clinical Research Cente
Ankara, 6800
Turkey (Türkiye)
Yeditepe University Kosuyolu Hospital
Istanbul, 34718
Turkey (Türkiye)
Queen Elizabeth Hospital
Birmingham, B15 2TH
United Kingdom
Velindre Cancer Centre
Cardiff, CF14 2TL
United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
United Kingdom
The Clatterbridge Cancer Centre
Liverpool, L7 8YA
United Kingdom
Royal Free Hospital
London, NW3 2QG
United Kingdom
Royal Marsden Hospital-London
London, SW3 6JJ
United Kingdom
Imperial College London
London, W12 0HS
United Kingdom
University College London Hospitals
London, W1T 7HA
United Kingdom
The Christie Hospital
Manchester, M20 4BX
United Kingdom
Northern Centre for Cancer Care
Newcastle upon Tyne, NE7 7DN
United Kingdom
Southampton General Hospital
Southampton, SO16 6YD
United Kingdom
Royal Marsden Hospital
Sutton, SM2 5PT
United Kingdom