New combo therapy aims to tackle tough lung cancer

NCT ID NCT07111520

Disease control Sponsor: BioNTech SE Source: ClinicalTrials.gov ↗

First seen Jun 25, 2026 · Last updated Aug 06, 2026 · Updated 3 times

Summary

This study tests two experimental drugs, BNT326 and BNT327, in people with advanced non-small cell lung cancer that has spread or come back. The trial has three parts to find the best dose and check safety, and will compare the combination to standard treatments like pembrolizumab or chemotherapy. About 420 adults are being recruited across multiple sites.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: BNT326 and BNT327 (investigational drugs) given by IV infusion, compared with pembrolizumab or standard chemotherapy
What this could lead to: If successful, this combination could offer a new treatment option for people with advanced lung cancer that has stopped responding to other therapies.
What could go wrong: This is an early-phase trial (Phase 1/2) with a small number of participants, so safety and effectiveness are not yet proven. Side effects from the drug combination are unknown and could be serious.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1/2

Runs two stages together: safety and dose first, then whether the treatment works.

Participants

About 880 people

The number the study aims to enrol. It can still change while the study runs.

Started

Sep 2025

Expected to finish

Jun 2030

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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 measurable disease defined by RECIST v1.1. * Have Eastern Cooperative Oncology Group performance status of 0 or 1. * Have adequate organ and bone marrow function within 7 days before randomization/enrollment as defined in the protocol. * Have advanced (i.e., metastatic or locally recurrent where local therapy with curative intent is not possible) non-squamous or squamous NSCLC. Cohort-specific inclusion criteria Part 1, 2L+, squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1 (NOTE: regimens used as neoadjuvant and/or adjuvant treatment may be considered as prior lines for advanced disease if relapse occurred within 6 months of the last dose.) * 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 in the metastatic setting, which can include anti-PD-1/PD-L1 therapy, chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. However, prior 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 tyrosine kinase inhibitor \[TKI\]) or sequentially. However, chemotherapy treatment must be limited to 2 lines or less. * Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance. * for AGA-positive NSCLC only (with EGFR activating mutation): * 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 TKI, with at least one being a third-generation EGFR TKI. * 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. * Chemotherapy is permitted only if it was 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. * Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance. Part 2a (Cohort A), 2L+, squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1 (NOTE: regimens used as neoadjuvant and/or adjuvant treatment may be considered as prior lines for advanced disease if relapse occurred within 6 months of the last dose.) * for AGA-positive NSCLC only, excluding EGFR activating mutation: * Have documented positive test results for one or more actionable genomic alterations: EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other genomic alterations, with available targeted therapy. * May have received 1 to 4 lines of systemic treatment, of which one prior systemic therapy for advanced disease 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 genomic alterations for which targeted therapies are available as part of local SoC. * Other therapies may include anti-PD-1/PD-L1 therapy, chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently/in combination (including with TKI) or sequentially. However, chemotherapy treatment must be limited to 2 lines or less. * Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance. * for AGA-positive NSCLC only, with EGFR activation mutation: * 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 TKI, with at least one being a third-generation EGFR TKI. * 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. * Chemotherapy is permitted only if it was 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. * Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance. Part 2a (Cohort B), 1L, squamous or non-squamous NSCLC, AGA-negative, any PD-L1 * Have no actionable genomic alterations, such as EGFR mutations, ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available. * Have received no systemic anti-cancer treatment in the advanced/metastatic setting. May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have not received treatment in the advanced/metastatic setting. Part 2b (Cohort C), 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1 * for AGA-negative NSCLC only: * Have no actionable genomic alterations, such as EGFR mutations, ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available. * Participants should have received 1 to 4 lines of systemic treatment, which can include anti-PD-1/PD-L1 therapy, chemotherapy, and/or anti-angiogenic agents. * Regimens used as neoadjuvant and/or adjuvant treatment may be considered as prior lines for advanced disease if relapse occurred within 6 months of the last dose. * for EGFR-sensitizing mutation NSCLC only: * Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del). * Have received 1 or 2 prior systemic therapies for advanced and/or metastatic disease with an approved EGFR TKI, which must include one third-generation anti-EGFR TKI. * 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. * Chemotherapy is permitted only if it was 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. * May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have experienced disease progression on or after EGFR TKI treatment administered in the advanced/metastatic setting. * Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance. Part 2b (Cohort D1) 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50% and Part 2b (Cohort D2) 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 \<50% * Have no actionable genomic alterations, such as EGFR mutations (Cohort D1)/EGFR-sensitizing mutations (Cohort D2), ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available. * Have not received prior systemic therapy for advanced and/or metastatic disease. May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have not received treatment in the advanced/metastatic setting. Key Exclusion Criteria (applicable to all participants and all parts): * 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 * Clinically significant 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 * Infectious colitis Grade ≥2 not resolved to Grade 1 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. * Have clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. * 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. * Are subject to exclusion periods from another investigational study. * Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP. * Have urine protein ≥2+ and 24-hour urine protein excretion ≥1 g. If qualitative urine protein is ≤1+, a 24-hour urine protein quantitative test is not required. * Have a history of Grade ≥3 immune-related adverse events that led to treatment discontinuation of a prior checkpoint inhibitor. * Have a significant risk of hemorrhage (per investigator clinical judgment) indicated by protocol defined criteria. * Have active or chronic clinically significant corneal disorders or any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy. NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

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Conditions

The condition(s) this trial relates to.

lethal congenital contracture syndrome 2 non-small cell lung carcinoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Non-small cell lung cancer

How to take part

Only the study team decides who joins. These are the ways to reach them.

The places running it

85 sites in 10 countries. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

Adana City Hospital
RECRUITING

Adana, 01230, Turkey (Türkiye)
Affiliated Hospital of Hebei University
RECRUITING

Baoding, 071000, China
Anhui Chest Hospital
RECRUITING

Hefei, 230022, China
Anhui Provincial Cancer Hospital
RECRUITING

Hefei, 230088, China
Ankara Memorial Hospital
RECRUITING

Ankara, 06520, Turkey (Türkiye)
Azienda Ospedaliera Universitaria Careggi
RECRUITING

Florence, 50134, Italy
Azienda Ospedaliero - Universitaria Nazionale Santi Antonio e Biagio e Cesare Arrigo
RECRUITING

Alessandria, 15100, Italy
Azienda Ospedaliero Universitaria Policlinico "Gaspare Rodolico - San Marco" (Presidio G. Rodolico)
RECRUITING

Catania, 95123, Italy
Baskent University Adana Application and Research Center
RECRUITING

Adana, 01240, Turkey (Türkiye)
Beijing GoBroad Hospital
RECRUITING

Beijing, 102200, China
Cancer Research SA
RECRUITING

Adelaide, 5000, Australia
Centrum Medyczne Pratia Poznan
RECRUITING

Poznan, 60-192, Poland
Chongqing University Cancer Hospital
RECRUITING

Chongqing, 400030, China
Cleveland Clinic Taussig Cancer Institute Case Comprehensive Cancer Center
RECRUITING

Cleveland, Ohio, 44195, United States
Clinica Universidad de Navarra
RECRUITING

Madrid, 31008, Spain
Clinica Universidad de Navarra
RECRUITING

Pamplona, 31008, Spain
Dana-Farber Cancer Institute
RECRUITING

Boston, Massachusetts, 02215, United States
Dr. Abdurrahman Yurtaslan Ankara Oncology Research and Training Hospital, Clinical Research Center
RECRUITING

Ankara, 06105, Turkey (Türkiye)
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
RECRUITING

Roma, 138, Italy
Fujian Provincial Cancer Hospital
RECRUITING

Fuzhou, 350014, China
Gazi University Medical Faculty
RECRUITING

Ankara, 06500, Turkey (Türkiye)
Georgetown University - Lombardi Comprehensive Cancer Center
RECRUITING

Washington D.C., District of Columbia, 20007, United States
Goztepe Prof. Dr. Suleyman Yalcin City Hospital
RECRUITING

Istanbul, 34722, Turkey (Türkiye)
Hacettepe University Medical Faculty
RECRUITING

Ankara, 06100, Turkey (Türkiye)
Henry Ford Health System
RECRUITING

Detroit, Michigan, 48202, United States
Hospital Clinic de Barcelona
RECRUITING

Barcelona, 08036, Spain
Hospital Quironsalud Malaga
RECRUITING

Málaga, 29004, Spain
Hospital Universitari Dexeus
RECRUITING

Barcelona, 08028, Spain
Hospital Universitari Vall d'Hebron - VHIO
RECRUITING

Barcelona, 08035, Spain
Hospital Universitari i Politecnic La Fe
RECRUITING

Valencia, 46026, Spain
Hospital Universitario 12 de Octubre
RECRUITING

Madrid, 28041, Spain
Hospital Universitario HM Madrid Sanchinarro
RECRUITING

Madrid, 28050, Spain
Hospital Universitario Reina Sofia
RECRUITING

Córdoba, 14004, Spain
Hospital Universitario Virgen Macarena
RECRUITING

Seville, 41009, Spain
Hubei Cancer Hospital
RECRUITING

Wuhan, 430079, China
IEO Istituto Europeo di Oncologia
RECRUITING

Milan, 20141, Italy
Institute of Oncology, ARENSIA Exploratory Medicine
RECRUITING

Chisinau, 2025, Moldova
Jinan Central Hospital
RECRUITING

Jinan, 250013, China
John Flynn Private Hospital
RECRUITING

Tugun, 4224, Australia
Koc University Hospital
RECRUITING

Istanbul, 34010, Turkey (Türkiye)
Mater
RECRUITING

South Brisbane, 4101, Australia
Med-Polonia Sp. z o.o.
RECRUITING

Poznan, 60-693, Poland
Medical Park Seyhan Hospital
RECRUITING

Adana, 01140, Turkey (Türkiye)
Memorial Antalya Hastanesi
RECRUITING

Antalya, 07020, Turkey (Türkiye)
Memorial Sloan Kettering Cancer Center
RECRUITING

New York, New York, 10065, United States
Mersin City Education and Research Hospital
RECRUITING

Mersin, 33330, Turkey (Türkiye)
Moffit Cancer Center
RECRUITING

Tampa, Florida, 33612, United States
NEXT Virginia
RECRUITING

Fairfax, Virginia, 22031, United States
Northern Centre for Cancer Care
RECRUITING

Newcastle upon Tyne, NE7 7DN, United Kingdom
Northern Jiangsu People's Hospital
RECRUITING

Yangzhou, 225001, China
Pratia ES Hospital Universitario de Torrejon
RECRUITING

Madrid, 28850, Spain
Pratia MCM Krakow
RECRUITING

Krakow, 30-727, Poland
Provita Prolife
RECRUITING

Tomaszów Mazowiecki, 97-200, Poland
Royal Free Hospital
RECRUITING

London, NW3 2QG, United Kingdom
Royal Marsden Hospital
RECRUITING

London, SW3 6JJ, United Kingdom
Royal Marsden Hospital-Sutton
RECRUITING

Sutton, SM2 5PT, United Kingdom
Royal North Shore Hospital
RECRUITING

Saint Leonards, 2065, Australia
Sakarya Training and Research Hospital
RECRUITING

Sakarya, 54290, Turkey (Türkiye)
Shanghai East Hospital
RECRUITING

Shanghai, 200120, China
Shanghai GoBroad Cancer Hospital
RECRUITING

Shanghai, 200120, China
St George Private Hospital
RECRUITING

Kogarah, 2217, Australia
Stanford Cancer Institute
RECRUITING

Stanford, California, 94305, United States
The Affiliated Hospital of Qingdao University
RECRUITING

Qingdao, 266003, China
The First Affiliated Hospital School of Clinical Medicine of Guangdong Pharmaceutical University
RECRUITING

Guangzhou, 510080, China
The First Affiliated Hospital of Anhui Medical University
RECRUITING

Hefei, 230022, China
The First Affiliated Hospital of Guangzhou Medical University
RECRUITING

Guangzhou, 510163, China
The First Affiliated Hospital of Nanchang University
RECRUITING

Nanchang, 330006, China
The First Affiliated Hospital of Soochow University
RECRUITING

Suzhou, 215006, China
The First Affiliated Hospital of Xinxiang Medical University
RECRUITING

Xinxiang, 453100, China
The First Hospital of Jilin University
RECRUITING

Changchun, 130021, China
The Second Affiliated Hospital of Nanchang University
RECRUITING

Nanchang, 330006, China
The Second Hospital of Anhui Medical University
RECRUITING

Hefei, 230601, China
Thoraxklinik Heidelberg gGmbH
RECRUITING

Heidelberg, 69126, Germany
Tianjin Medical University Cancer Institute & Hospital
RECRUITING

Tianjin, 300060, China
UCLA Hematology Oncology - Main Site
RECRUITING

Los Angeles, California, 90095, United States
University of Texas M. D. Anderson Cancer Center
RECRUITING

Houston, Texas, 77030, United States
Universitätsklinikum Carl Gustav Carus TU Dresden
RECRUITING

Dresden, 01307, Germany
Universitätsklinikum Freiburg
RECRUITING

Freiburg im Breisgau, 79106, Germany
Uniwersyteckie Centrum Kliniczne
RECRUITING

Gdansk, 80-214, Poland
West China Hospital, Sichuan University
RECRUITING

Chengdu, 611135, China
Westmead Hospital
RECRUITING

Westmead, 2145, Australia
Xiangyang Central Hospital
RECRUITING

Xiangyang, 441138, China
Xuzhou Central Hospital
RECRUITING

Xuzhou, 221009, China
Yale University
RECRUITING

New Haven, Connecticut, 06511, United States
Yeditepe University Medical School Hospital
RECRUITING

Istanbul, 31755, Turkey (Türkiye)

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