Safety, Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Small-cell Lung Cancer in Combination With Chemotherapy

NCT06449209 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: BNT327-01
• Study Type: interventional
• Target: 110
• Locations: 5 countries
• Sites: 64

Brief Summary

This is a Phase II, multi-site, open-label, parallel group study in participants with untreated extended-stage small-cell lung cancer (ES-SCLC) (Cohort 1) or small-cell lung cancer (SCLC) which has progressed on first- or second-line treatment (Cohort 2 and Cohort 3). This study will assess the safety, efficacy, and pharmacokinetics (PK) of BNT327.

Conditions

Extensive-stage Small-cell Lung Cancer; Small-cell Lung Cancer

Keywords

Programmed Death-1 (PD-1); Programmed Death Ligand-1 (PD-L1); Programmed Death-1 monoclonal antibodies; Combination chemotherapy; Anti vascular endothelial growth factor (VEGF); Previously treated small-cell lung cancer; Untreated extensive-stage small-cell lung cancer; Dose optimization; Time to progression

Outcome Measures

Primary Outcomes (5)

• Occurrence of treatment emergent adverse events (TEAEs), adverse events of special interest (AESIs), treatment-related TEAEs, treatment-related serious adverse events (SAEs) and treatment-related treatment emergent SAEs

  In the combination treatment regimen according to the (US) National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0). By treatment arm and overall.

  up to 100 days after the last dose of treatment

• Occurrence of dose interruption, reduction, and discontinuation of study treatment due to TEAEs

  By treatment arm and overall.

  up to 100 days after the last dose of treatment

• Objective Response Rate

  Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\] based on the investigator's assessment) is observed as best overall response. By treatment arm.

  up to 24 months after completion of study treatment of the last participant

• Best percentage change from baseline in the tumor size

  Based on the investigator's tumor assessment according to RECIST 1.1. Defined as the change from baseline in percent to the minimal tumor size until tumor progression/recurrence or death (whichever comes first). By treatment arm.

  up to 24 months after completion of study treatment of the last participant

• Proportion of participants who have achieved early tumor shrinkage

  Defined as ≥10% decrease in the pretreatment sum of diameters at first post-treatment tumor scan in target lesions. By treatment arm.

  up to 2 months after first dose of treatment

Secondary Outcomes (10)

• PK assessment: Maximum concentration (Cmax) derived from serum concentration of investigational medicinal product (IMP)

  from pre-dose to 21 days after study treatment

• PK assessment: Area under the curve during the dosing interval (AUCtau) values derived from serum concentration of IMP

  from pre-dose to 21 days after study treatment

• Incidence of detectable BNT327 antidrug antibodies in serum

  from pre-dose to 100 days after last dose of study treatment

• Duration of Response

  up to 24 months after completion of study treatment of the last participant

• Disease Control Rate

  up to 24 months after completion of study treatment of the last participant

Study Arms (6)

Cohort 1 Arm 1 - BNT327 DL1 + carboplatin + etoposide

EXPERIMENTAL

Participants with ES-SCLC without prior systemic anticancer therapy received in the ES setting

Drug: BNT327 Dose Level 1 (DL1); Drug: Etoposide; Drug: Carboplatin

Cohort 1 Arm 2 - BNT327 DL2 + carboplatin + etoposide

EXPERIMENTAL

Participants with ES-SCLC without prior systemic anticancer therapy received in the ES setting

Drug: BNT327 Dose Level 2 (DL2); Drug: Etoposide; Drug: Carboplatin

Cohort 2 Arm 1 - BNT327 DL1 + paclitaxel

EXPERIMENTAL

Participants with SCLC who have disease progression/relapse

Drug: BNT327 Dose Level 1 (DL1); Drug: Paclitaxel

Cohort 2 Arm 2 - BNT327 DL2 + paclitaxel

EXPERIMENTAL

Participants with SCLC who have disease progression/relapse

Drug: BNT327 Dose Level 2 (DL2); Drug: Paclitaxel

Cohort 3 Arm 1 - BNT327 DL1 + topotecan

EXPERIMENTAL

Participants with SCLC who have disease progression/relapse

Drug: BNT327 Dose Level 1 (DL1); Drug: Topotecan

Cohort 3 Arm 2 - BNT327 DL2 + topotecan

EXPERIMENTAL

Participants with SCLC who have disease progression/relapse

Drug: BNT327 Dose Level 2 (DL2); Drug: Topotecan

Interventions

BNT327 Dose Level 1 (DL1) DRUG

Intravenous (IV) infusion

Cohort 1 Arm 1 - BNT327 DL1 + carboplatin + etoposide; Cohort 2 Arm 1 - BNT327 DL1 + paclitaxel; Cohort 3 Arm 1 - BNT327 DL1 + topotecan

BNT327 Dose Level 2 (DL2) DRUG

IV infusion

Cohort 1 Arm 2 - BNT327 DL2 + carboplatin + etoposide; Cohort 2 Arm 2 - BNT327 DL2 + paclitaxel; Cohort 3 Arm 2 - BNT327 DL2 + topotecan

Etoposide DRUG

IV infusion

Cohort 1 Arm 1 - BNT327 DL1 + carboplatin + etoposide; Cohort 1 Arm 2 - BNT327 DL2 + carboplatin + etoposide

Carboplatin DRUG

IV infusion

Cohort 1 Arm 1 - BNT327 DL1 + carboplatin + etoposide; Cohort 1 Arm 2 - BNT327 DL2 + carboplatin + etoposide

Paclitaxel DRUG

IV infusion

Cohort 2 Arm 1 - BNT327 DL1 + paclitaxel; Cohort 2 Arm 2 - BNT327 DL2 + paclitaxel

Topotecan DRUG

IV infusion or oral capsules

Cohort 3 Arm 1 - BNT327 DL1 + topotecan; Cohort 3 Arm 2 - BNT327 DL2 + topotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1 only: Have histologically or cytologically confirmed ES-SCLC (using the American Joint Committee on Cancer \[AJCC\]) tumor node metastasis \[TNM\] staging system combined with Veterans Administration Lung Study Group two-stage classification scheme). For AJCC TNM staging system: AJCC 8th edition stage IV (T any, N any, M1a/b/c), or T3\~4 for multiple lung nodules or tumor/nodule volume that cannot be encompassed in a tolerable radiotherapy plan.
• Cohort 1 only: Participants who have not received systemic therapy for ES-SCLC for various reasons including potential intolerance of the standard-of-care per the patient's treating physician's judgment. However, participants with prior chemoradiotherapy for Limited-Stage Small-Cell Lung Cancer (LS-SCLC) must have been treated with curative intent and had a treatment-free interval of at least 6 months since the last systemic anticancer treatment including chemotherapy, radiotherapy, or chemoradiotherapy before the diagnosis of ES-SCLC to be eligible.
• Cohort 2 and Cohort 3 only: Participants with SCLC who have disease progression/relapse after first-line platinum-based chemotherapy with or without immunotherapy, or after first-line platinum-based chemotherapy and one second-line of chemotherapy (not the same chemotherapy agent in the specific arm to be enrolled to) with time to progression ≥3 months during second-line treatment.
• Have given informed consent by signing and dating an informed consent form before initiation of any study-specific procedures.
• Male or female, aged ≥18 years at the time of giving informed consent.
• Are willing and able to comply with scheduled visits, treatment schedule, the planned study assessments, laboratory tests, lifestyle restrictions, and other requirements of the study. This includes that they are able to understand and follow study-related instructions.
• Have at least one measurable lesion as the targeted lesion based on RECIST 1.1. Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures, etc.) are generally not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system metastasis should not be considered as a measurable lesion).
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Have a minimum life expectancy of \>3 months.
• Have adequate organ function, as defined below:
• Hematology:
• Absolute neutrophil count ≥1.5 × 10\^9/L.
• Platelet count ≥100 × 10\^9/L.
• Hemoglobin ≥90 g/L or 5.6 mmol/L.
• Liver function:

You may not qualify if:

• Are pregnant or breastfeeding or are planning pregnancy or planning to father children during the study or within 6 months after the last dose of IMP.
• Have a medical, psychological, or social condition which, in the opinion of the investigator, could compromise their wellbeing if they participate in the study, or that could prevent, limit, or confound the protocol-specified assessments or procedures, or that could impact adherence to protocol-described requirements.
• Have histologically or cytologically confirmed SCLC with combined histologies.
• Have received any of the following therapies or drugs within the noted time intervals prior to the initiation of study treatment:
• Within 2 weeks: small molecule targeted agents with half-life of \<7 days; or radiation not involving the thoracic cavity; local radiation for brain lesion is allowed; local radiation for bone lesions is allowed.
• Within 4 weeks: radiation involving the thoracic cavity; small molecule targeted agents with half-life of ≥7 days; monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies.
• Participants who received prior treatment with a PDL-1/VEGF bispecific antibody.
• Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 10 days prior to the initiation of study treatment. Note: The following are allowed: local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short-term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).
• Have been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of the study treatment.
• Received broad-spectrum intravenous antibiotics therapy within 2 weeks prior to initiation of study treatment.
• Use of any non-study IMP within 3 weeks before initiation of study treatment in this study or ongoing participation in the active treatment phase of another interventional clinical study.
• Have undergone major organ surgery (core needle biopsies are allowed \>7 days prior study start), significant trauma, or invasive dental procedures (such as dental implants) within 28 days prior to the initiation of study treatment or plan to undergo elective surgery during the study. Placement of vascular infusion devices is allowed.
• Have received allogeneic hematopoietic stem cell transplantation or organ transplantation.
• Have the following central nervous system metastases:
• Participants with untreated brain metastases that are symptomatic or large (e.g., \>2 cm).

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (64)

Alaska Oncology and Hematology, LLC

Anchorage, Alaska, 99508, United States

Location

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

Location

Clermont Oncology Center

Clermont, Florida, 34711, United States

Location

Hematology Oncology Associates of Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Tallahassee Memorial Physician Partners - Cancer & Hematology Specialists

Tallahassee, Florida, 32308, United States

Location

Carle Foundation Hospital d/b/a Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Fort Wayne Medical Oncology and Hematology, Inc

Fort Wayne, Indiana, 46804, United States

Location

University of Kentucky Chandler Medical Center (UKCMC) - Markey Cancer Center (Lucille P. Markey Cancer Center)

Lexington, Kentucky, 40536, United States

Location

Allina Health

Minneapolis, Minnesota, 55407, United States

Location

SSM Health Cancer Care - St. Clare

Fenton, Missouri, 63026, United States

Location

Nebraska Hematology-Oncology (NHO) - Lincoln

Lincoln, Nebraska, 68506, United States

Location

Clinical Research Alliance Inc

Westbury, New York, 11590, United States

Location

Haywood Infusion Center

Clyde, North Carolina, 28721-8046, United States

Location

FirstHealth Outpatient Cancer Center

Pinehurst, North Carolina, 28374, United States

Location

The Christ Hospital Cancer Center

Cincinnati, Ohio, 45219, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Millenium Research & Clinical Development

Houston, Texas, 77090, United States

Location

SSM Health Cancer Care

Madison, Wisconsin, 53715, United States

Location

Lyell McEwin Hospital

Adelaide, 5112, Australia

Location

St. Vincent's Hospital

Fitzroy, 3065, Australia

Location

Peninsula Oncology Centre

Frankston, 3199, Australia

Location

Royal North Shore Hospital

St Leonards, 2065, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

Chungbuk National University Hospital

Cheongju-si, 28644, South Korea

Location

Yeungnam University Medical Center

Daegu, 42415, South Korea

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Gyeongsang National University Hospital (GNUH)

Jinju, 52727, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

The Catholic University of Korea Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

Ajou University Hospital

Suwon, 16499, South Korea

Location

Baskent University Hospital Adana Dr Turgut Noyan Research Center

Adana, 01120, Turkey (Türkiye)

Location

Medical Park Seyhan Hospital

Adana, 01230, Turkey (Türkiye)

Location

Adana City Training and Research Hospital

Adana, 4522, Turkey (Türkiye)

Location

Gulhane Egitim ve Arastirma Hastanesi

Ankara, 06010, Turkey (Türkiye)

Location

Ankara Etlik Sehir Hastanesi

Ankara, 06170, Turkey (Türkiye)

Location

Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital

Ankara, 06200, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty Oncology Hospital

Ankara, 06230, Turkey (Türkiye)

Location

Memorial Ankara Hospital

Ankara, 06520, Turkey (Türkiye)

Location

Liv Hospital

Ankara, 06680, Turkey (Türkiye)

Location

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Gaziantep Sanko University Medical Faculty

Gaziantep, 36020, Turkey (Türkiye)

Location

Koc Universitesi Hastanesi (Koc University Hospital)

Istanbul, 34010, Turkey (Türkiye)

Location

Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi

Istanbul, 34093, Turkey (Türkiye)

Location

Acibadem Adana Hastanesi

Istanbul, 34457, Turkey (Türkiye)

Location

Yeditepe University Kosuyolu Hospital

Istanbul, 34718, Turkey (Türkiye)

Location

Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi

Istanbul, 34722, Turkey (Türkiye)

Location

Medical Point Izmir Hospital

Izmir, 35325, Turkey (Türkiye)

Location

Kocaeli Universitesi Tip Fakultesi

Kocaeli, 41380, Turkey (Türkiye)

Location

Sakarya University - Faculty of Medicine

Sakarya, 54290, Turkey (Türkiye)

Location

Namik Kemal University Hospital

Tekirdağ, 59030, Turkey (Türkiye)

Location

Gazi University Medical Faculty

Yenimahalle, 06560, Turkey (Türkiye)

Location

Queen Elizabeth Hospital Birmingham - University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2GW, United Kingdom

Location

Velindre Hospital - Velindre NHS Trust

Cardiff, CF14 2TL, United Kingdom

Location

Ninewells Hospital and Medical School - Tayside Health Board

Dundee, DD1 9SY, United Kingdom

Location

Royal Devon and Exeter Hospital, Wonford - Royal Devon And Exeter NHS Foundation Trust

Exeter, EX2 5DW, United Kingdom

Location

Huddersfield Royal Infirmary - Calderdale and Huddersfield NHS Foundation Trust

Huddersfield, HD3 3EA, United Kingdom

Location

St James's University Hospital - Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

Northern Centre for Cancer Care,The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

Royal Preston Hospital - Lancashire Teaching Hospitals NHS Foundation Trust

Preston, PR2 9HT, United Kingdom

Location

Royal Stoke University Hospital - University Hospitals of North Midlands NHS Trust

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Etoposide; Carboplatin; Paclitaxel; Topotecan

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 7, 2024
• Study Start: August 5, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); US (18); KR (9); TU (21); GB (11)