Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer (LuCa-MERIT-1)

LuCa-MERIT-1: First-in-human, Open Label, Phase I Dose Confirmation Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer

This first-in-human (FIH) study for BNT116 aims to establish the safety profile and a safe dose for BNT116 monotherapy as well as for BNT116 in combination with approved medicinal products and/or in combination with investigational medicinal products (IMPs) including, but not limited to, cemiplimab, docetaxel, carboplatin, paclitaxel, osimertinib, anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), rearranged during transfection (RET) TKIs, BNT316 (an anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] antibody), an anti-B7-H3 antibody conjugated to a topoisomerase I inhibitor, an anti-human epidermal growth factor receptor 3 (HER3) antibody conjugated to a topoisomerase I inhibitor or a bispecific antibody for programmed death ligand 1 (PD-L1) and vascular endothelial growth factor A (VEGF-A) in participants with non-small cell lung cancer (NSCLC).

The study will comprise several cohorts for dose confirmation in monotherapy as well as in combinations of BNT116 as mentioned above.

The study will enroll participants with NSCLC in advanced or metastatic stage in Cohorts 1 to 4 and Cohorts 7 to 10, unresectable NSCLC Stage III in Cohorts 5 and 11, resectable NSCLC of Stage II and III in Cohort 6, advanced/metastatic epidermal growth factor receptor (EGFR)-mutant NSCLC in Cohort EGFR, and advanced/metastatic ALK rearranged or RET rearranged NSCLC in Cohort ALK/RET.

Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Paclitaxel; Drug: Carboplatin; Biological: BNT116; Biological: Cemiplimab; Biological: BNT316; Biological: anti-B7-H3 antibody conjugated to topoisomerase I inhibitor; Biological: anti-HER3 antibody conjugated to topoisomerase I inhibitor; Biological: Bispecific antibody for PD-L1 and VEGF-A; Biological: Osimertinib; Biological: ALK-inhibitor or RET-inhibitor

Detailed Description

The maximum duration of treatment for each individual participant in this study is:

• Cohorts 1 to 4, Cohorts 7 to 10, Cohort EGFR, and Cohort ALK/RET: 24 months.
• Cohorts 5 and 11: 18 cycles, i.e., 12 months.
• Cohort 6: 4 cycles of neo-adjuvant treatment and 18 cycles of adjuvant treatment, i.e., 12 months of adjuvant treatment.

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: BioNTech clinical trials patient information; Phone Number: +49 6131 9084; Email: patients@biontech.de

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Recruiting
      • Scientia Clinical Research
    • Sydney, New South Wales, Australia, 2065
      • Recruiting
      • Royal North Shore Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Cancer Research SA
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Health
• Germany
  • Cologne, Germany, 50937
    • Recruiting
    • Universitätsklinikum Köln
  • Frankfurt, Germany, 60488
    • Recruiting
    • Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)
  • Hamburg, Germany, 20246
    • Recruiting
    • University Medical Center Hamburg-Eppendorf
  • Mainz, Germany, 55131
    • Recruiting
    • Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
• Hungary
  • Budapest, Hungary, 1122
    • Recruiting
    • National Institute of Oncology
  • Budapest, Hungary, 1083
    • Recruiting
    • Semmelweis Egyetem ÁOK Belgyógyászati és Onkológiai Klinika
  • Budapest, Hungary, 1077
    • Completed
    • ICON-PRA Budapest, Fázis 1 Vizsgálóhely
  • Gyöngyös, Hungary, 3200
    • Recruiting
    • Clinexpert Ltd
• Poland
  • Gdansk, Poland, 80-214
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Olsztyn, Poland, 10-357
    • Recruiting
    • Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie
  • Poznan, Poland, 60-693
    • Recruiting
    • NZOZ Medpolonia Sp. Z o.o
  • Warsaw, Poland, 02-781
    • Withdrawn
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
• Spain
  • Badalona, Spain, 08916
    • Recruiting
    • Institut Catala d'Oncologia Badalona, Hospital Germans Trias I Pujol
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28033
    • Recruiting
    • MD Anderson Cancer Center
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28050
    • Recruiting
    • START Madrid - CIOCC. Grupo Hospital de Madrid (HM) - Centro Integral Oncologico Clara Campal (CIOCC)
  • Santiago de Compostela, Spain, 15706
    • Recruiting
    • Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) - Hospital Clinico Universitario (University Clinical Hospital)
  • Seville, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitario y Politécnico La FE
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01370
    • Recruiting
    • Adana City Training and Research Hospital
  • Ankara, Turkey (Türkiye), 06800
    • Recruiting
    • Ankara City Hospital
  • Ankara, Turkey (Türkiye), 06100
    • Recruiting
    • Haceteppe Hospital
  • Ankara, Turkey (Türkiye), 06200
    • Recruiting
    • Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital
  • Istanbul, Turkey (Türkiye), 34010
    • Recruiting
    • Koç University Hospital
  • Istanbul, Turkey (Türkiye), 34718
    • Recruiting
    • Yeditepe University
  • Istanbul, Turkey (Türkiye), 34093
    • Recruiting
    • University Medical Faculty Oncology Institute
  • Izmir, Turkey (Türkiye), 35100
    • Recruiting
    • Ege University School of Medicine Tulay Aktas Oncology Hospital
  • Izmir, Turkey (Türkiye), 35330
    • Completed
    • Dokuz Eylul Medical School
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Recruiting
    • Cambridge University Hospitals NHS Foundation Trust
  • Cardiff, United Kingdom, CF14 2TL
    • Recruiting
    • Velindre NHS Trust
  • Liverpool, United Kingdom, L7 8YA
    • Recruiting
    • The Clatterbridge Cancer Centre NHS Foundation Trust
  • London, United Kingdom, W1T 7HA
    • Recruiting
    • University College London Hospitals NHS Foundation Trust
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's and St Thomas NHS Foundation Trust
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Recruiting
    • The Newcastle Upon Tyne Hospitals NHS Foundation Trust
• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University of Kentucky Chandler Medical Center
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Next Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participants must have histologically confirmed NSCLC and measurable disease by RECIST v1.1. Note: Participants in Cohorts 1, 5 and 11 do not have to present with measurable disease.

  1. Participants must present with unresectable Stage III or metastatic Stage IV NSCLC by American Joint Commission on Cancer (AJCC) Cancer Staging Manual, Eighth Edition.

     EXCEPT

  2. Participants in Cohorts 5 and 11 must present with unresectable Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition before receiving pre-study chemoradiotherapy.
  3. Participants in Cohort 6 with the initial diagnosis of resectable Stage II and Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition.
• Participants in Cohorts 2, 4, 5, 6, 10 and 11 must be able to tolerate (additional) anti-PD-1 therapy (i.e., did not permanently discontinue anti-programmed death protein 1 [PD-1] / programmed death ligand 1 [PD-L1] therapy due to toxicity).
• Participants must have an Eastern Cooperative Oncology Group performance status (ECOG-PS) less than or equal to (<=) 1, except for participants in Cohorts 1, 4, 5, 10 and 11 who are eligible with an ECOG-PS of 0-2.

Cohort-specific inclusion criteria:

Cohort 1:

• Participants' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen as well as one other line of systemic therapy (except if a participant is not candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor and/or another line of systemic therapy). Note: Participants newly enrolled in Cohort 1B under protocol v 5.0 and subsequent versions of the protocol must consent to mandatory blood sampling for peripheral blood mononuclear cells (PBMCs).
• Participants who are to start cemiplimab at Cycle 3 must present with PD-L1 expression of tumor proportion score (TPS) greater than or equal to (>=) 1% in tumor cells (as determined locally).

Cohort 2:

• Participants must present with PD-L1 expression of tumor proportion score (TPS) >= 50% in tumor cells (as determined locally prior to inclusion in this study).

• Participants must present with progressive disease either

  1. in the advanced or metastasized stage of NSCLC: while on a PD-1/PD-L1 inhibitor therapy or within 6 months of termination of this treatment as first-line treatment. Or
  2. be refractory to ongoing adjuvant therapy/maintenance treatment after CRT with a PD-1/PD-L1 inhibitor that has been given for at least 3 months in monotherapy (i.e., after an initial combination therapy) before being enrolled into this study.

Cohort 3:

• Participants' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a participant is not candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor).
• Participants must present with progressive disease.

Cohort 4:

• Participants who are not candidates for chemotherapy as first-line treatment for the advanced or metastasized stage of NSCLC may be enrolled if presenting with PD-L1 expression: TPS >= 1% in tumor cells (as determined locally).

Cohort 5:

• Participants' NSCLC must have been considered unresectable due to participant's condition and/or tumor-related factors and the participants must have undergone chemoradiotherapy before entering the study.

Cohort 6:

• Participants' NSCLC must be considered technically and medically resectable.
• Participants must be considered eligible for neo-adjuvant treatment.

Cohort 7:

• Participants' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a participant is not a candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor). Note 1: Participants may have received prior therapy targeting CTLA-4, lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif [ITIM] domain (TIGIT), VEGF or VEGF receptor (VEGFR) inhibitor as monotherapy or part of a combination therapy. Note 2: If the participants' prior therapies included a CTLA-4 inhibitor, the participant must be able to tolerate (additional) treatment with the CTLA-4 inhibitor.
• Participants must present with progressive disease at study enrollment.
• Participants must consent to mandatory blood sampling for PBMCs.

Cohorts 8 & 9:

• Participants' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a participant is not a candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor).
• Participants must present with progressive disease at study enrollment.

Cohort 10:

• Participants who are not candidates for chemotherapy as first-line treatment for the advanced or metastasized stage of NSCLC may be enrolled.

Cohort 11:

• Participants' NSCLC must have been considered unresectable due to participants condition and/or tumor related factors and the participants must have undergone chemoradiotherapy before entering the study.

Cohort EGFR (will enroll only at selected sites in the US):

• Participants' NSCLC must have classical EGFR mutations, i.e., ex19Del or L858R.
• Participants must have ongoing treatment with osimertinib.

Cohort ALK/RET (will enroll only at selected sites in the US):

• Participants' NSCLC must have ALK rearrangement or RET rearrangement.
• Participants must have ongoing treatment with a standard of care ALK TKI or RET TKI.

Key Exclusion Criteria:

• Ongoing active systemic treatment against NSCLC.
• Presence of a driver mutation for which approved target therapies are available except if the participant is not a candidate for the respective targeted therapy. EXCEPT participants in Cohort EGFR and Cohort ALK/RET.
• Ongoing or recent evidence (within the last 5 years) of significant autoimmune disease that required treatment with systemic immunosuppressive treatments which may suggest risk for immune-related adverse events. Note: Participants with autoimmune-related hyperthyroidism, autoimmune-related hypothyroidism who are in remission, or on a stable dose of thyroid-replacement hormone, vitiligo, or psoriasis may be included.
• Current evidence of new or growing brain or spinal metastases during screening. Participants with leptomeningeal disease are excluded. Participants with known brain or spinal metastases may be eligible for all Cohorts, except for Cohorts 5, 6 and 11, if they:
• had radiotherapy or another appropriate therapy for the brain or spinal metastases, AND
• have no neurological symptoms that can be attributed to the current brain lesions, AND
• have stable brain or spinal disease on the computed tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the informed consent (confirmed by stable lesions on two scans at least 4 weeks apart), AND
• do not require steroid therapy for the treatment of brain or spinal metastases within 14 days before the first dose of study treatment. Note: Spinal bone metastases (that is, of the vertebrae) are allowed, unless imminent fracture or cord compression is anticipated.
• Systemic immune suppression:
• Current use of chronic systemic steroid medication (<= 5 mg/day prednisolone equivalent is allowed); participants using physiological replacement doses of prednisone for adrenal or pituitary insufficiency are eligible. Note: Steroid medication given for supportive or prophylactic reasons during CRT for participants in Cohorts 5 and 11 needs to be tapered to <= 5 mg/day prednisolone equivalent at latest on the day before the study treatment starts.
• Other clinically relevant systemic immune suppression within the last 3 months before study enrollment.
• Known history of seropositivity for human immunodeficiency virus (HIV) with cluster of differentiation 4 (CD4)+ T-cell (CD4+) counts less than (<) 350 cells/microlitre (mcL) and with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections.
• Prior splenectomy.
• History/risk of interstitial lung disease or low baseline lung function (baseline pulse oximetry of less than 92% oxygen saturation [SpO2] without additional oxygen).

NOTE: Other protocol defined Inclusion/Exclusion criteria apply to all or some participants depending on the cohort.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 7 - BNT116 + BNT316; Dose finding for the combination of BNT116 with BNT316 (CTLA4 antibody) with dose escalation of BNT316	Biological: BNT116; Intravenous injection; Biological: BNT316; Intravenous infusion
Experimental: Cohort 1A - BNT116 Monotherapy	Biological: BNT116; Intravenous injection
Experimental: Cohort 1B - BNT116 Monotherapy	Biological: BNT116; Intravenous injection
Experimental: Cohort 2 - BNT116 + Cemiplimab (PD-1/PD-L1 Inhibitor Refractory/Relapsed Participants)	Biological: BNT116; Intravenous injection; Biological: Cemiplimab; Intravenous infusion
Experimental: Cohort 3 - BNT116 + Docetaxel	Drug: Docetaxel; Intravenous infusion; Biological: BNT116; Intravenous injection
Experimental: Cohort 4 - BNT116 + Cemiplimab (Frail Participants)	Biological: BNT116; Intravenous injection; Biological: Cemiplimab; Intravenous infusion
Experimental: Cohort 5 - BNT116 + Cemiplimab (After Concurrent Chemoradiotherapy [CRT])	Biological: BNT116; Intravenous injection; Biological: Cemiplimab; Intravenous infusion
Experimental: Cohort 6 - BNT116 + Cemiplimab + Carboplatin + Paclitaxel; BNT116 + cemiplimab + carboplatin + paclitaxel as neo-adjuvant treatment followed by surgery, thereafter adjuvant treatment with BNT116 + cemiplimab	Drug: Paclitaxel; Intravenous infusion; Drug: Carboplatin; Intravenous infusion; Biological: BNT116; Intravenous injection; Biological: Cemiplimab; Intravenous infusion
Experimental: Cohort 8: BNT116 + Anti-B7-H3 Antibody Conjugated to Topoisomerase I Inhibitor; Dose finding for the combination of BNT116 with an anti-B7-H3 antibody conjugated to a topoisomerase I inhibitor with dose escalation of the anti-B7-H3 antibody conjugated to a topoisomerase I inhibitor	Biological: BNT116; Intravenous injection; Biological: anti-B7-H3 antibody conjugated to topoisomerase I inhibitor; Intravenous infusion
Experimental: Cohort 9: BNT116 + Anti-HER3 Antibody Conjugated to Topoisomerase I Inhibitor; Dose confirmation for the combination of BNT116 with an anti-HER3 antibody conjugated to a topoisomerase I inhibitor with dose escalation of the anti-HER3 antibody conjugated to a topoisomerase I inhibitor	Biological: BNT116; Intravenous injection; Biological: anti-HER3 antibody conjugated to topoisomerase I inhibitor; Intravenous infusion
Experimental: Cohort 10: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (Frail Participants); Dose confirmation for BNT116 in combination with a bispecific antibody for programmed death ligand 1 (PD-L1) and vascular endothelial growth factor A (VEGF-A) will be established.	Biological: BNT116; Intravenous injection; Biological: Bispecific antibody for PD-L1 and VEGF-A; Intravenous infusion
Experimental: Cohort 11: BNT116 + Bispecific Antibody for PD-L1 and VEGF-A (After Concurrent CRT); Dose confirmation for BNT116 in combination with a bispecific antibody for PD-L1 and VEGF-A will be established in participants after concurrent CRT.	Biological: BNT116; Intravenous injection; Biological: Bispecific antibody for PD-L1 and VEGF-A; Intravenous infusion
Experimental: Cohort EGFR : BNT116 + osimertinib; Dose confirmation for BNT116 in combination with ongoing osimertinib therapy. Treatment with osimertinib is standard of care. Cohort will enroll only at selected sites in the US.	Biological: BNT116; Intravenous injection; Biological: Osimertinib; Oral
Experimental: Cohort ALK/RET: BNT116 + ALK TKI or RET TKI; Dose confirmation for BNT116 in combination with either ongoing ALK-inhibitor or ongoing RET-inhibitor therapy. Treatment with ALK TKI or RET TKI is standard of care. Cohort will enroll only at selected sites in the US.	Biological: BNT116; Intravenous injection; Biological: ALK-inhibitor or RET-inhibitor; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 6 only: Occurrence of Post-Surgical Adverse Events (AEs) Related to BNT116 and Cemiplimab		up to 27 months
Cohort 6 only: Occurrence of Treatment-Related Delays to Surgery More Than 9 weeks Post the Last Dose of Neo-Adjuvant Treatment		up to 6 months
Cohorts 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, EGFR and ALK/RET: Occurrence of Dose-Limiting Toxicities (DLTs) During the DLT Observation Period	Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.	From first dose of IMP up to 21 days
Cohorts 1 to 11, EGFR and ALK/RET: Occurrence of Treatment-Emergent Adverse Events (TEAEs) Reported by Relationship, Seriousness, and Grade	According to National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0). Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.	up to 27 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Response (DoR)	DoR defined as the time from initial response until first objective tumor progression according to RECIST v1.1.	up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Disease Control	Duration of disease control defined as the time from initial detection of stable disease or response until first objective tumor progression according to RECIST v1.1.	up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Overall Response Rate (ORR)	ORR defined as the number of participants with complete response (CR) or partial response (PR) as best overall response (BOR) according to response evaluation criteria in solid tumors (RECIST) v1.1 divided by the number of participants in the efficacy analysis set.	up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Disease Control Rate (DCR)	DCR defined as the number of participants with CR or PR or stable disease (SD) as BOR according to RECIST v1.1 divided by the number of participants in the efficacy analysis set.	up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Progression-Free Survival (PFS)	PFS defined as the time of first study treatment until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first.	up to 48 months
Cohorts EGFR (osimertinib): PFS	Defined as the time of first treatment with osimertinib until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first. Cohort EGFR will enroll only at selected sites in the US.	up to 48 months
Cohort ALK/RET (ALK TKI or RET TKI): PFS	Defined as the time of first treatment with a ALK TKI or RET TKI until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first. Cohort ALK/RET will enroll only at selected sites in the US.	up to 48 months
Cohorts EGFR and ALK/RET: (BNT116): PFS per molecular NSCLC subtype	Defined as the time of first treatment with BNT116 until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first. Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.	up to 48 months
Cohorts 1-11: Overall Survival (OS)	OS defined as the time of first study treatment until death from any cause.	up to 48 months
Cohorts 5, 6 and 11: Event Free Survival (EFS)	EFS defined as the length of time from first study treatment to any of the following events: progression of disease, recurrence of disease or death from any cause, whichever occurs first.	up to 48 months
Cohort 6: Rate of Pathologic Responses	Rate of pathologic responses defined as the number of participants with major or complete pathologic response in the surgical specimen from surgery after neo-adjuvant study treatment divided by the number of participants in the efficacy analysis set.	At time of surgery (approximately after 3 months treatment)
Cohorts 5, 6 and 11: EFS Rate at 12 and 24 months	EFS rate defined as the number of participants without an EFS-defining event divided by the number of participants in the efficacy analysis set.	up to 24 months
Cohort 6: ORR at the End of Neo-Adjuvant Treatment (Using RECIST v1.1)	ORR defined as the number of participants with CR or PR as BOR according to RECIST v1.1 divided by the number of participants in the efficacy analysis set.	up to 3 months
Cohort 6: Rate of Progressive Disease at the End of Neo-Adjuvant Treatment (Using RECIST v1.1)		up to 3 months

Collaborators and Investigators

• Sponsor: BioNTech SE
• Investigators: Study Director: BioNTech Responsible Person, BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2022
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): November 1, 2031

Study Registration Dates

• First Submitted: November 24, 2021
• First Submitted That Met QC Criteria: November 24, 2021
• First Posted (Actual): December 2, 2021

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Non-Small Cell Lung Cancer; Immunotherapy; Cancer Vaccine; Antibody-drug conjugate (ADC); Combination with chemotherapy; Combination with other investigational agents; anti-B7-H3 antibody conjugated to topoisomerase I inhibitor; anti-HER3 antibody conjugated to topoisomerase I inhibitor; Anaplastic lymphoma kinase (ALK) rearranged Non-Small Cell Lung Cancer; Rearranged during transfection (RET) rearranged Non-Small Cell Lung Cancer; anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody; Epidermal growth factor receptor (EGFR)-mutant Non-Small Cell Lung Cancer; Combination with a programmed cell death protein 1 (PD-1) inhibitor; Human epidermal growth factor receptor 3
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Genetic Diseases, Inborn; Respiratory Tract Diseases; Lung Diseases; Endocrine Gland Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Syndromes, Hereditary; Neoplasms, Multiple Primary; Multiple Endocrine Neoplasia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Carcinoma, Non-Small-Cell Lung; Multiple Endocrine Neoplasia Type 2a; Parkinson Disease 4, Autosomal Dominant Lewy Body; Diabetes Mellitus, Insulin-Dependent, 12; Lethal Congenital Contracture Syndrome 2; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Biological Factors; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Intercellular Signaling Peptides and Proteins; Angiogenic Proteins; Vascular Endothelial Growth Factors; Docetaxel; Carboplatin; Antibodies, Bispecific; Paclitaxel; osimertinib; cemiplimab; Vascular Endothelial Growth Factor A
• Other Study ID Numbers: BNT116-01; 2021-004739-94 (EudraCT Number); 2023-509283-14-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No