Clinical trial • Phase I/II • Oncology

BNT326 for Non-small cell lung cancer

Phase I/II trial of BNT326 for Non-small cell lung cancer. open-label, none/not specified-controlled, adaptive. 332 participants.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Non-small cell lung cancer
Trial Stage
Phase I/II
Drug Modality
ADC|Monoclonal antibody|Small molecule

Key dates

Initial CTIS Submission Date
06-08-2025
First CTIS Authorization Date
02-12-2025

Trial design

open-label, none/not specified-controlled, adaptive Phase I/II trial across 33 sites in Germany, Italy, Spain and others.

Open Label
Yes
Comparator
None/Not specified
Adaptive
True, dose-escalation design to determine recommended phase 2 dose (RP2D) with a DLT evaluation period; includes dose expansion and dose optimization cohorts (Part 1 dose escalation; Part 2a dose expansion; Part 2b dose optimization).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
332

Eligibility

Recruits 332 No vulnerable population selected; trial enrols adults only (Aged ≥18). Informed consent is required from participants. No assent or parental consent provisions are described in the provided materials..

Pregnancy Exclusion
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.
Vulnerable Population
No vulnerable population selected; trial enrols adults only (Aged ≥18). Informed consent is required from participants. No assent or parental consent provisions are described in the provided materials.

Inclusion criteria

  • {"criterion_text":"- Aged ≥18 years at the time of giving informed consent.\n- Have measurable disease defined by RECIST v1.1.\n- All participants have to provide a tumor tissue sample from archival tissue. Alternatively, a fresh biopsy should be collected, unless medically not justifiable to be conducted.\n- Have Eastern Cooperative Oncology Group performance status of 0 or 1.\n- Have adequate organ and bone marrow function within 7 days before randomization/enrollment.\n- All parts: Have advanced non-squamous or squamous NSCLC."}

Exclusion criteria

  • {"criterion_text":"- Had disease progression on or were intolerant to prior treatment with an agent targeting HER3 or with a topoisomerase I inhibitor payload. 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.\n- 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.\n- Have a history of Grade ≥3 immune-related adverse events that led to treatment discontinuation of a prior checkpoint inhibitor.\n- Have clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.\n- Participants with significant risks of hemorrhage or evidence of major coagulation disorders.\n- Have active or chronic corneal disorders or with any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.\n- Have an uncontrolled concomitant or intercurrent illness, that contraindicates study participation, limits compliance with study procedures or substantially increases the risk of incurring adverse events (AEs).\n- Have left ventricular ejection fraction < 50 % by either echocardiography or multi-gated acquisition within 28 days before randomization/enrollment.\n- 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.\n- Cohort C: 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1: Are eligible for 2L therapy with amivantamab in combination with chemotherapy.\n- Have had exposure to protocol-specific treatments with a washout period before randomization/enrollment.\n- 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.\n- Are subject to exclusion periods from another investigational study.\n- Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.\n- Cohort C: 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1: Are eligible for 2L therapy with amivantamab in combination with chemotherapy."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Part 1 - Occurrence of dose limiting toxicities (DLTs) within a participant during the DLT evaluation period","definition_or_measurement_approach":"Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period (DLT assessment window defined in protocol)."}
  • {"endpoint_text":"- 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)","definition_or_measurement_approach":"Collection and reporting of TEAEs, TRAEs, TESAEs and TRSAEs per protocol safety monitoring procedures."}
  • {"endpoint_text":"- Part 1 and Part 2a - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs","definition_or_measurement_approach":"Recording of any dose interruption, dose reduction or discontinuation attributable to TEAEs as documented in participant treatment records."}
  • {"endpoint_text":"- Part 2a and Part 2b - Objective response rate (ORR): Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) is observed as best overall response.","definition_or_measurement_approach":"ORR measured as proportion with confirmed CR or PR (per RECIST v1.1) as best overall response."}

Secondary endpoints

  • {"endpoint_text":"- Part 1 – ORR: Defined as the percentage of participants in whom a confirmed CR or PR (per RECIST v1.1 based on the investigator’s assessment) is observed as best overall response.","definition_or_measurement_approach":"ORR per RECIST v1.1 based on investigator assessment; percentage of participants with confirmed CR or PR."}
  • {"endpoint_text":"- Part 2b - Occurrence of TEAEs, TRAEs, TESAEs, TRSAEs","definition_or_measurement_approach":"Collection and reporting of TEAEs, TRAEs, TESAEs and TRSAEs per protocol safety monitoring procedures."}
  • {"endpoint_text":"- Part 2b - Occurrence of dose interruption, reduction, and discontinuation due to TEAEs","definition_or_measurement_approach":"Recording of dose modifications and discontinuations due to TEAEs."}
  • {"endpoint_text":"- Part 2a and Part 2b - Progression free survival based on the investigator's assessment: Defined as the time from first dose of IMP to the first objective tumor progression or death from any cause, whichever occurs first.","definition_or_measurement_approach":"PFS measured from first IMP dose to first objective tumor progression or death (investigator assessment)."}
  • {"endpoint_text":"- Part 2a and Part 2b - Disease control rate: Defined as the proportion of participants with CR, PR, or stable disease as best overall response.","definition_or_measurement_approach":"Disease control rate = proportion with CR, PR, or stable disease as best overall response (per RECIST v1.1)."}
  • {"endpoint_text":"- Part 2a and Part 2b - Duration of response: Defined as the time from first confirmed objective response (CR or PR per RECIST v1.1 based on the investigator’s assessment) to first occurrence of objective tumor progression or death from any cause, whichever occurs first","definition_or_measurement_approach":"Duration measured from first confirmed CR/PR to first objective progression or death."}
  • {"endpoint_text":"- Part 2a and Part 2b - Time to response: Defined as the time from first dose of IMP to first confirmed objective response in participants with a confirmed objective response","definition_or_measurement_approach":"Time from first dose to first confirmed objective response (CR/PR)."}
  • {"endpoint_text":"- Part 2a and Part 2b - Overall survival: Defined as the time from first dose of IMP to death from any cause","definition_or_measurement_approach":"Overall survival measured from first IMP dose to death from any cause."}
  • {"endpoint_text":"- All cohorts - PK assessment: Maximum concentration derived from serum concentrations of BNT326 ADC, total anti-HER3 antibody component, and unconjugated payload. For applicable participants, if data permits.","definition_or_measurement_approach":"PK assessment includes Cmax derived from serum concentrations of BNT326 ADC, total anti-HER3 antibody component, and unconjugated payload."}
  • {"endpoint_text":"- All cohorts - PK assessment: Time to reach maximum (peak) serum concentration derived from serum concentrations of BNT326 ADC, total anti-HER3 antibody component, and unconjugated payload. For applicable participants, if data permits.","definition_or_measurement_approach":"PK assessment includes time to Cmax (Tmax) for BNT326 ADC and components."}
  • {"endpoint_text":"- All cohorts - Anti-drug antibody (ADA) prevalence and ADA incidence. By cohort and combination treatment regimen for applicable participants.","definition_or_measurement_approach":"Immunogenicity assessment measuring ADA prevalence and incidence by cohort and regimen."}

Recruitment

Digital Remote Recruitment
True, study includes Patient Pre-screening Website Content (digital pre-screening materials) and web-based informational content for potential participants.
Planned Sample Size
332
Recruitment Window Months
36
Consent Approach
Informed consent required from participants (participants must be aged ≥18). Subject information and informed consent forms are provided; ICF documents and participant information sheets are available in multiple local-language versions (examples in German, Italian, Spanish, Polish and English variants are present among provided ICF/SIS documents). No assent/parental consent described.

Methods

  • Physician referral letters (K2_RecruitMat_Physician Referral Letter; country-specific versions present) - channel: physician-to-physician letters to refer eligible patients; target audience: treating clinicians; country-specific versions (e.g., DEU, ITA, ESP, POL) included in recruitment materials.
  • Doctor-to-Patient letters (K2_RecruitMat_Doctor-to-Patient Letter / K2_Dr-to-Patient Letter) - channel: clinician-delivered letters to patients; target audience: potential participants; country-specific versions present.
  • Patient brochure (K2_RecruitMat_Patient Brochure / K2_Patient Brochure) - channel: printed/digital brochure for patients; target audience: potential participants; country-specific versions present (DEU, ITA, ESP, POL).
  • Patient pre-screening website content (K2_RecruitMat_Patient Pre-screening Website Content / K2_ Patient Informational Website Content) - channel: online pre-screening content; target audience: potential participants for self-pre-screening; country/language-specific versions available.
  • Study information slides and doctor/patient informational slides (K2_RecruitMat_Study Information Slides) - channel: presentation/slide materials for information sessions; target audience: clinicians and patients; versions available for multiple countries.

Geography

Total Number Of Sites
33
Total Number Of Participants
332

Germany

Earliest CTIS Part Ii Submission Date
13-11-2025
Latest Decision Or Authorization Date
08-12-2025
Processing Time Days
25
Number Of Sites
7
Number Of Participants
22

Sites

Site Name
Technische Universitaet Dresden
Department Name
Studiensekretariat Onkologie, Haus 31 Zimmer 217
Contact Person Name
Martin Wermke
Site Name
Goethe University Frankfurt
Department Name
Med. Klinik II
Contact Person Name
Martin Sebastian
Contact Person Email
sebastian@med.uni-frankfurt.de
Site Name
Thoraxklinik Heidelberg gGmbH
Department Name
Studienzentrum Thoraxonkologie
Contact Person Name
Michael Thomas
Site Name
Medical Center - University Of Freiburg
Department Name
Klinik für Innere Medizin I
Contact Person Name
Cornelius Waller
Site Name
Universitaetsklinikum Essen AöR
Department Name
Department of Medical Oncology
Contact Person Name
Gregor Zaun
Contact Person Email
gregor.zaun@uk-essen.de
Site Name
Universitaetsmedizin Goettingen
Department Name
Department of Hematology and Medical Oncology
Contact Person Name
Tobias Overbeck
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Campus Benjamin Franklin - Studienzentrale Onkologie
Contact Person Name
Sebastian Ochsenreither

Italy

Earliest CTIS Part Ii Submission Date
25-08-2025
Latest Decision Or Authorization Date
02-12-2025
Processing Time Days
99
Number Of Sites
8
Number Of Participants
24

Sites

Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
UOC Oncologia Medica
Contact Person Name
Emilio Bria
Site Name
Azienda Ospedaliero Universitaria Careggi
Department Name
SODc Clinical Oncology
Contact Person Name
Lorenzo Antonuzzo
Site Name
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
Department Name
Medical oncology
Contact Person Name
Hector Josè Soto Parra
Contact Person Email
hsotoparra@yahoo.it
Site Name
Azienda Ospedaliero-Universitaria Ss.Antonio E Biagio E C.Arrigo Alessandria
Department Name
S.C. Oncologia
Contact Person Name
Pier Luigi Piovano
Contact Person Email
plpiovano@ospedale.al.it
Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
SC Oncologia Falck, Niguarda Cancer Center
Contact Person Name
Giulio Cerea
Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
New drugs development for innovative therapies
Contact Person Name
Dario Trapani
Contact Person Email
Dario.trapani@ieo.it
Site Name
Azienda Ospedaliera Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
PRECISION MEDICINE - UNIVERSITY OF CAMPANIA
Contact Person Name
Carminia Maria Della Corte
Site Name
Azienda Ospedaliero-Universitaria Senese
Department Name
UOC Immunoterapia Oncologica
Contact Person Name
Michele Maio
Contact Person Email
maio@unisi.it

Spain

Earliest CTIS Part Ii Submission Date
12-11-2025
Latest Decision Or Authorization Date
09-12-2025
Processing Time Days
27
Number Of Sites
13
Number Of Participants
26

Sites

Site Name
Hospital Universitario De Torrejon
Department Name
Oncology
Contact Person Name
Luis Cabezon Gutierrez
Contact Person Email
lcabezon@torrejonsalud.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncology
Contact Person Name
Enriqueta Felip Font
Contact Person Email
efelip@vhio.net
Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology
Contact Person Name
Santiago Ponce Aix
Contact Person Email
santiago.ponce@oncosur.org
Site Name
Hospital Universitario Reina Sofia
Department Name
Oncology
Contact Person Name
Isidoro Carlos Barneto Aranda
Contact Person Email
isidoroc.barneto@gmail.com
Site Name
Clinica Universidad De Navarra (Madrid)
Department Name
Oncology
Contact Person Name
Miguel Fernandez de Sanmamed Gutierrez
Contact Person Email
msanmamed@unav.es
Site Name
Hospital Clinic De Barcelona
Department Name
Oncology
Contact Person Name
Noemi Reguart Aransay
Contact Person Email
nreguart@clinic.cat
Site Name
Hospital Universitari Dexeus Grupo Quironsalud
Department Name
Oncology
Contact Person Name
Andrés Aguilar Hernandez
Contact Person Email
aaguilar@oncorosell.com
Site Name
Clinica Universidad De Navarra (Pamplona)
Department Name
Oncology
Contact Person Name
Miguel Fernandez de Sanmamed Gutierre
Contact Person Email
msanmamed@unav.es
Site Name
Complejo Hospitalario Universitario Insular Materno Infantil
Department Name
Oncology
Contact Person Name
Delvys Rodriguez Abreu
Contact Person Email
drodabr@gobiernodecanarias.org
Site Name
Hospital Quironsalud Malaga
Department Name
Oncology
Contact Person Name
Manuel Cobo Dols
Contact Person Email
manuelcobodols@yahoo.es
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Oncology
Contact Person Name
Oscar José Juan Vidal
Contact Person Email
juan_osc@gva.es
Site Name
Hospital Universitario Virgen De La Macarena
Department Name
Oncology
Contact Person Name
David Vicente Baz
Contact Person Email
david.vbaz@gmail.com
Site Name
Hospital Universitario Hm Sanchinarro
Department Name
Oncology
Contact Person Name
Ramón Yarza Barrio
Contact Person Email
Ramon.Yarza@startmadrid.com

Poland

Earliest CTIS Part Ii Submission Date
17-11-2025
Latest Decision Or Authorization Date
08-12-2025
Processing Time Days
21
Number Of Sites
5
Number Of Participants
16

Sites

Site Name
Pratia S.A. (Poznan)
Department Name
Site name: Pratia Poznań
Contact Person Name
Marek Kotlarski
Contact Person Email
marek.kotlarski@pratia.com
Site Name
Pratia S.A. (Cracow)
Department Name
Site name: Pratia MCM Kraków
Contact Person Name
Anna Drosik-Kwaśniewska
Contact Person Email
anna.drosik@pratia.pl
Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Site name:Centrum Wsparcia Badań Klinicznych, Ośrodek Badań Klinicznych Wczesnych Faz
Contact Person Name
Katarzyna Szymczak
Contact Person Email
kszymczak@uck.gda.pl
Site Name
Provita Centrum Medyczne Sp. z o.o.
Department Name
Site name: Provita Prolife
Contact Person Name
Magdalena Ciążyńska
Contact Person Email
ciazynska.magdalena@gmail.com
Site Name
Med Polonia Sp. z o.o.
Contact Person Name
Rodryg Ramlau

Sponsor

Primary sponsor

Full Name
BioNTech SE
Organisation Type
Pharmaceutical company
Country Of Registered Address
Germany

Contract research organisations

Name
IQVIA Limited
Responsibilities
Vendor Management, Project Management, Data Management
Name
Almac Clinical Services LLC
Responsibilities
IMP supply management, secondary packaging and labelling
Name
Almac Clinical Services Limited
Responsibilities
IMP supply management, secondary packaging and labelling, QP release and distribution
Name
Pharmaceutical Research Associates Group B.V.
Responsibilities
Pharmacokinetic and ADA for BNT326

Third parties

  • {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"3","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Specialty Lab (Histology, IHC) & Central lab","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"BioAgilytix Europe GmbH","duties_or_roles":"Pharmacokinetic and ADA for BNT327","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Vendor Management, Project Management, Data Management","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"IMP supply management, secondary packaging and labelling","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"central lab for the study, histology for exploratory endpoints and research, processing of blood samples for exploratory research e.g. ctDNA etc.","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Pharmaceutical Research Associates Group B.V.","duties_or_roles":"Pharmacokinetic and ADA for BNT326","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"IMP supply management, secondary packaging and labelling, QP release and distribution","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"Speciality lab for ctDNA analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Long-Term storage","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
BNT326
Active Substance
BNT326
Modality
ADC
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
1
Investigational Product Name
BNT327
Active Substance
BNT327
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
1
Investigational Product Name
PEMBROLIZUMAB
Active Substance
PEMBROLIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
2
Investigational Product Name
PEMETREXED DISODIUM
Active Substance
PEMETREXED DISODIUM
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
2
Investigational Product Name
CARBOPLATIN
Active Substance
CARBOPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
2
Investigational Product Name
PACLITAXEL
Active Substance
PACLITAXEL
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
2
Combination Treatment
Yes

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