A Clinical Trial to Test if an Investigational Combination Therapy With BNT326 and BNT327 is Safe and Potentially Beneficial for People With Advanced Non-small Cell Lung Cancer (NSCLC)
A Phase Ib/II, Multi-site, Open-label, Dose Finding Trial to Evaluate the Safety, Efficacy, and Pharmacokinetics of BNT326 in Combination With BNT327 in Participants With Advanced Non-small Cell Lung Cancer (NSCLC)
2 other identifiers
interventional
420
10 countries
68
Brief Summary
This is a multi-site, open-label, dose-finding study, consisting of Parts 1, 2a, and 2b to investigate the combination of BNT326 with BNT327 in participants with relapsed, progressive as well as treatment-naïve, advanced/metastatic non-small cell lung cancer (NSCLC). This study will enroll adult participants with histologically or cytologically confirmed NSCLC that is advanced (i.e., either metastatic or recurrent tumors with no known curative treatment available).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 nonsmall-cell-lung-cancer
Started Sep 2025
Typical duration for phase_1 nonsmall-cell-lung-cancer
68 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 1, 2025
CompletedFirst Posted
Study publicly available on registry
August 8, 2025
CompletedStudy Start
First participant enrolled
September 22, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2030
May 5, 2026
April 1, 2026
3.3 years
August 1, 2025
April 29, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Part 1 - Occurrence of dose limiting toxicities (DLTs) within a participant
During the DLT evaluation period by dose level
21 days starting on Day 1 of Cycle 1
Part 1 and Part 2a - Occurrence of treatment emergent adverse events (TEAEs), treatment-related adverse events (TRAE), treatment emergent serious adverse events (TESAE), treatment-related serious adverse events (TRSAE)
from the first dose of investigational medicinal product (IMP) up to 90 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to a maximum of 27 months)
Part 1 and Part 2a - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs
from the first dose of IMP up to 90 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to a maximum of 27 months)
Part 2a and Part 2b - Objective response rate (ORR)
Defined as the percentage of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] based on the investigator's assessment) is observed as best overall response.
from the time of initiation of the first dose of IMP to approximately 36 months
Secondary Outcomes (11)
Part 1 - ORR
from the time of initiation of the first dose of IMP to approximately 36 months
Part 2b - Occurrence of TEAEs, TRAEs, TESAEs, TRSAEs
from the first dose of IMP up to 90 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to a maximum of 27 months)
Part 2b - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs
from the first dose of IMP up to 90 days after the last dose of IMP or until a new systemic anti-cancer therapy is started, whichever occurs first (up to a maximum of 27 months)
Part 2a and Part 2b - Progression free survival based on the investigator's assessment
from the first dose of IMP to approximately 36 months
Part 2a and Part 2b - Disease control rate
from the first dose of IMP to approximately 36 months
- +6 more secondary outcomes
Study Arms (15)
Part 1 - BNT326 (DL1, starting dose) + BNT327
EXPERIMENTALCombination therapy of BNT326 and BNT327. In participants with second-line (or higher) 2L(+), squamous or non-squamous NSCLC, actionable genomic alterations (AGA)-negative/positive, any PD-L1.
Part 1 - BNT326 (DL2) + BNT327
EXPERIMENTALCombination therapy of BNT326 and BNT327. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1.
Part 1 - BNT326 (DL3, optional) + BNT327
EXPERIMENTALCombination therapy of BNT326 and BNT327. In participants with 2L(+), squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1.
Part 2a (Cohort A, Arm 1) - BNT326 (DL1) + BNT327
EXPERIMENTALCombination therapy of BNT326 and BNT327. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1.
Part 2a (Cohort A, Arm 2) - BNT326 (DL2) + BNT327
EXPERIMENTALCombination therapy of BNT326 and BNT327. In participants with 2L+ squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1.
Part 2a (Cohort B, Arm 1) - BNT326 (DL1) + BNT327
EXPERIMENTALCombination therapy of BNT326 and BNT327. In participants with first-line (1L) squamous or non-squamous NSCLC, AGA-negative, any PD-L1.
Part 2a (Cohort B, Arm 2) - BNT326 (DL2) + BNT327
EXPERIMENTALCombination therapy of BNT326 and BNT327. In participants with 1L squamous or non-squamous NSCLC, AGA-negative, any PD-L1.
Part 2b (Cohort C, Arm 1) - BNT326 (DL1) + BNT327
EXPERIMENTALCombination therapy of BNT326 and BNT327. In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or epithelial growth factor receptor (EGFR) activating mutation, any PD-L1.
Part 2b (Cohort C, Arm 2) - BNT326 (DL2) + BNT327
EXPERIMENTALCombination therapy of BNT326 and BNT327. In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1.
Part 2b (Cohort C, Arm 3) - BNT326 monotherapy
EXPERIMENTALBNT326 monotherapy (DL2). In participants with 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1.
Part 2b (Cohort D1, Arm 1) - BNT326 (DL2) + BNT327
EXPERIMENTALCombination therapy of BNT326 and BNT327. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%.
Part 2b (Cohort D1, Arm 2) - Pembrolizumab
ACTIVE COMPARATORPembrolizumab monotherapy. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%.
Part 2b (Cohort D1, Arm 3) - BNT327 monotherapy
EXPERIMENTALBNT327 monotherapy. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50%.
Part 2b (Cohort D2, Arm 1) - BNT326 (DL2) + BNT327
EXPERIMENTALCombination therapy of BNT326 and BNT327. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 \<50%.
Part 2b (Cohort D2, Arm 2) - SoC - Pembrolizumab + chemotherapy
ACTIVE COMPARATORCombination therapy of pembrolizumab and chemotherapy. In participants with 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 \<50%.
Interventions
intravenous (IV) infusion
IV infusion
IV infusion
IV infusion. Combination chemotherapy (pemetrexed, paclitaxel, or carboplatin). Chemotherapy will be selected according to the indication.
Eligibility Criteria
You may qualify if:
- Aged ≥18 years at the time of giving informed consent.
- Have measurable disease defined by RECIST v1.1.
- All participants have to provide a tumor tissue sample (e.g. Formalin-fixed paraffin-embedded \[FFPE\] slides or block) from archival tissue. Alternatively, a fresh biopsy should be collected, unless medically not justifiable to be conducted.
- Have Eastern Cooperative Oncology Group performance status of 0 or 1.
- Have adequate organ and bone marrow function within 7 days before randomization/enrollment.
- Have advanced (i.e., metastatic or locally recurrent where local therapy with curative intent is not possible) non-squamous or squamous (all cohorts) or only non-squamous (Cohort D2) NSCLC.
- Part 1, 2L+, squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1
- for AGA-negative NSCLC only:
- Have no actionable genomic alterations, such as EGFR mutations, anaplastic lymphoma kinase (ALK) gene rearrangements, or other genomic alterations for which targeted molecular therapies are available.
- Have experienced relapse or progression during or after treatment with standard systemic therapy 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, chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. However, chemotherapy treatment must be limited to 2 lines or less.
- for AGA-positive NSCLC only (excluding EGFR activating mutation):
- Have documented positive test results for one or more actionable genomic alteration: EGFR (other than activating mutations), ALK, ROS proto-oncogene 1 (ROS1), gene encoding the hepatocyte growth factor receptor (MET), human gene that encodes a protein called B-Raf (BRAF), rearranged during transfection (RET), neurotrophic tropomyosin-receptor kinase (NTRK), human epidermal growth factor receptor 2 (HER2), Kirsten rat sarcoma virus (KRAS), or other genomic alteration with available targeted therapy.
- Must have received at least one prior systemic therapy for advanced disease, which must have included targeted treatment for actionable genomic alterations, which include alterations such as EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other alterations for which targeted therapies are available as a part of local SoC.
- Participants may have received between 1 to 3 lines of systemic treatment of anti-PD-1/PD-L1 therapy, chemotherapy, and/or anti-angiogenic agents. These treatments may be administered concurrently (including with TKI) or sequentially. However, chemotherapy treatment must be limited to 2 lines or less.
- +36 more criteria
You may not qualify if:
- Had disease progression on or were intolerant to prior treatment with an agent targeting HER3 (including antibody, ADC, cell therapy, and other drugs) or with a topoisomerase I inhibitor payload (including topoisomerase I inhibitor-containing ADCs). Note: For Part 2a Cohort A, prior exposure to agents targeting HER3 or topoisomerase I inhibitor payload may be allowed on a case-by-case basis after discussion with and approval by the sponsor.
- Have an uncontrolled concomitant or intercurrent illness, that contra-indicates study participation, limits compliance with study procedures or substantially increases the risk of incurring AEs, including:
- Bleeding diathesis or active hemorrhage
- Active infection, including respiratory viral infection
- Child-Pugh class B or C cirrhosis
- Known pulmonary disease with significant impact in lung function and/or with potential risk of severe infection
- 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
- Colitis Grade ≥2 not resolved within 72 h within the past 3 months
- Have left ventricular ejection fraction \<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.
- Have had exposure to protocol-specific treatments with a washout period before randomization/enrollment.
- Are participants of childbearing potential who are pregnant or breastfeeding or are planning pregnancy within the time specified in the protocol or are potentially fertile males, who are planning to father children during the study or within the time specified in the protocol.
- Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- BioNTech SElead
- MediLink Therapeutics (Suzhou) Co., Ltd.collaborator
Study Sites (68)
Stanford Cancer Institute
Stanford, California, 94305, United States
Yale University
New Haven, Connecticut, 06511, United States
Moffit Cancer Center
Tampa, Florida, 33612, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Cleveland Clinic Taussig Cancer Institute Case Comprehensive Cancer Center
Cleveland, Ohio, 44195, United States
University of Texas M. D. Anderson Cancer Center
Houston, Texas, 77030, United States
NEXT Virginia
Fairfax, Virginia, 22031, United States
Cancer Research SA
Adelaide, 5000, Australia
St George Private Hospital
Kogarah, 2217, Australia
John Flynn Private Hospital
Tugun, 4224, Australia
Westmead Hospital
Westmead, 2145, Australia
Affiliated Hospital of Hebei University
Baoding, 071000, China
Beijing GoBroad Hospital
Beijing, 102200, China
The First Hospital of Jilin University
Changchun, 130021, China
West China Hospital, Sichuan University
Chengdu, 611135, China
Chongqing University Cancer Hospital
Chongqing, 400030, China
The First Affiliated Hospital School of Clinical Medicine of Guangdong Pharmaceutical University
Guangzhou, 510080, China
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, 510163, China
Anhui Chest Hospital
Hefei, 230022, China
The First Affiliated Hospital of Anhui Medical University
Hefei, 230022, China
Anhui Provincial Cancer Hospital
Hefei, 230088, China
The Second Hospital of Anhui Medical University
Hefei, 230601, China
Jinan Central Hospital
Jinan, 250013, China
The First Affiliated Hospital of Nanchang University
Nanchang, 330006, China
The Second Affiliated Hospital of Nanchang University
Nanchang, 330006, China
The Affiliated Hospital of Qingdao University
Qingdao, 266003, China
Shanghai East Hospital
Shanghai, 200120, China
Shanghai GoBroad Cancer Hospital
Shanghai, 200120, China
The First Affiliated Hospital of Soochow University
Suzhou, 215006, China
Tianjin Medical University Cancer Institute & Hospital
Tianjin, 300060, China
Hubei Cancer Hospital
Wuhan, 430079, China
Xiangyang Central Hospital
Xiangyang, 441138, China
The First Affiliated Hospital of Xinxiang Medical University
Xinxiang, 453100, China
Northern Jiangsu People's Hospital
Yangzhou, 225001, China
Universitätsklinikum Carl Gustav Carus TU Dresden
Dresden, 01307, Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
Azienda Ospedaliero - Universitaria Nazionale Santi Antonio e Biagio e Cesare Arrigo
Alessandria, 15100, Italy
Azienda Ospedaliera Universitaria Careggi
Florence, 50134, Italy
Institute of Oncology, ARENSIA Exploratory Medicine
Chisinau, 2025, Moldova
Pratia MCM Krakow
Krakow, 30-727, Poland
Centrum Medyczne Pratia Poznan
Poznan, 60-192, Poland
Med-Polonia Sp. z o.o.
Poznan, 60-693, Poland
Provita Prolife
Tomaszów Mazowiecki, 97-200, Poland
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Universitario HM Madrid Sanchinarro
Madrid, 28050, Spain
Clinica Universidad de Navarra
Madrid, 31008, Spain
Hospital Quironsalud Malaga
Málaga, 29004, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
Medical Park Seyhan Hospital
Adana, 01140, Turkey (Türkiye)
Adana City Hospital
Adana, 01230, Turkey (Türkiye)
Baskent University Adana Application and Research Center
Adana, 01240, Turkey (Türkiye)
Hacettepe University Medical Faculty
Ankara, 06100, Turkey (Türkiye)
Dr. Abdurrahman Yurtaslan Ankara Oncology Research and Training Hospital, Clinical Research Center
Ankara, 06105, Turkey (Türkiye)
Gazi University Medical Faculty
Ankara, 06500, Turkey (Türkiye)
Ankara Memorial Hospital
Ankara, 06520, Turkey (Türkiye)
Memorial Antalya Hastanesi
Antalya, 07020, Turkey (Türkiye)
Yeditepe University Medical School Hospital
Istanbul, 31755, Turkey (Türkiye)
Koc University Hospital
Istanbul, 34010, Turkey (Türkiye)
Goztepe Prof. Dr. Suleyman Yalcin City Hospital
Istanbul, 34722, Turkey (Türkiye)
Mersin City Education and Research Hospital
Mersin, 33330, Turkey (Türkiye)
Sakarya Training and Research Hospital
Sakarya, 54290, Turkey (Türkiye)
Royal Free Hospital
London, NW3 2QG, United Kingdom
Royal Marsden Hospital
London, SW3 6JJ, United Kingdom
Northern Centre for Cancer Care
Newcastle upon Tyne, NE7 7DN, United Kingdom
Royal Marsden Hospital-Sutton
Sutton, SM2 5PT, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
BioNTech Responsible Person
BioNTech SE
Central Study Contacts
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
August 1, 2025
First Posted
August 8, 2025
Study Start
September 22, 2025
Primary Completion (Estimated)
January 1, 2029
Study Completion (Estimated)
January 1, 2030
Last Updated
May 5, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share