Safety, Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Small-cell Lung Cancer in Combination With Chemotherapy
- Conditions
- Extensive-stage Small-cell Lung CancerSmall-cell Lung Cancer
- Interventions
- Drug: BNT327 Dose Level 1 (DL1)Drug: BNT327 Dose Level 2 (DL2)
- Registration Number
- NCT06449209
- Lead Sponsor
- BioNTech SE
- 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.
- Detailed Description
In Cohort 1 of this study, two dose levels of BNT327 will be studied in combination with etoposide and carboplatin to identify an optimized dose for future clinical investigation.
Cohort 2 and Cohort 3 will explore the combination of two dose levels of BNT327 with paclitaxel, or topotecan in the second- or third-line setting.
Patients will be treated until disease progression, intolerable toxicity, patient withdrawal, study termination or up to 2 years (whichever occurs first).
Participants will be assigned to either Cohort 1 or Cohort 2/Cohort 3 based on their disease type (i.e., untreated ES-SCLC for Cohort 1 and SCLC which has progressed on first- or second-line treatment for Cohort 2 and Cohort 3). Assignment to either Cohort 2 or Cohort 3 will be the investigator's choice.
Participants will be randomized to each arm within each cohort:
* Participants enrolled to Cohort 1 and Cohort 3 will be randomized in a 1:1 ratio to Arm 1 or Arm 2.
* Participants enrolled to Cohort 2 will be randomized in a 2:1 ratio to Arm 1 or Arm 2.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 110
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 Arm 1 - BNT327 DL1 + carboplatin + etoposide BNT327 Dose Level 1 (DL1) Participants with ES-SCLC without prior systemic anticancer therapy received in the ES setting Cohort 1 Arm 1 - BNT327 DL1 + carboplatin + etoposide Etoposide Participants with ES-SCLC without prior systemic anticancer therapy received in the ES setting Cohort 1 Arm 1 - BNT327 DL1 + carboplatin + etoposide Carboplatin Participants with ES-SCLC without prior systemic anticancer therapy received in the ES setting Cohort 1 Arm 2 - BNT327 DL2 + carboplatin + etoposide BNT327 Dose Level 2 (DL2) Participants with ES-SCLC without prior systemic anticancer therapy received in the ES setting Cohort 1 Arm 2 - BNT327 DL2 + carboplatin + etoposide Etoposide Participants with ES-SCLC without prior systemic anticancer therapy received in the ES setting Cohort 1 Arm 2 - BNT327 DL2 + carboplatin + etoposide Carboplatin Participants with ES-SCLC without prior systemic anticancer therapy received in the ES setting Cohort 2 Arm 1 - BNT327 DL1 + paclitaxel BNT327 Dose Level 1 (DL1) Participants with SCLC who have disease progression/relapse Cohort 2 Arm 1 - BNT327 DL1 + paclitaxel Paclitaxel Participants with SCLC who have disease progression/relapse Cohort 2 Arm 2 - BNT327 DL2 + paclitaxel BNT327 Dose Level 2 (DL2) Participants with SCLC who have disease progression/relapse Cohort 2 Arm 2 - BNT327 DL2 + paclitaxel Paclitaxel Participants with SCLC who have disease progression/relapse Cohort 3 Arm 1 - BNT327 DL1 + topotecan BNT327 Dose Level 1 (DL1) Participants with SCLC who have disease progression/relapse Cohort 3 Arm 1 - BNT327 DL1 + topotecan Topotecan Participants with SCLC who have disease progression/relapse Cohort 3 Arm 2 - BNT327 DL2 + topotecan BNT327 Dose Level 2 (DL2) Participants with SCLC who have disease progression/relapse Cohort 3 Arm 2 - BNT327 DL2 + topotecan Topotecan Participants with SCLC who have disease progression/relapse
- Primary Outcome Measures
Name Time Method 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 up to 100 days after the last dose of treatment 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.
Occurrence of dose interruption, reduction, and discontinuation of study treatment due to TEAEs up to 100 days after the last dose of treatment By treatment arm and overall.
Objective Response Rate up to 24 months after completion of study treatment of the last participant 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.
Best percentage change from baseline in the tumor size up to 24 months after completion of study treatment of the last participant 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.
Proportion of participants who have achieved early tumor shrinkage up to 2 months after first dose of treatment Defined as ≥10% decrease in the pretreatment sum of diameters at first post-treatment tumor scan in target lesions. By treatment arm.
- Secondary Outcome Measures
Name Time Method PK assessment: Maximum concentration (Cmax) derived from serum concentration of investigational medicinal product (IMP) from pre-dose to 21 days after study treatment By treatment arm. Only for the first cycle.
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 By treatment arm. Only for the first cycle.
Incidence of detectable BNT327 antidrug antibodies in serum from pre-dose to 100 days after last dose of study treatment By treatment arm and overall.
Duration of Response up to 24 months after completion of study treatment of the last participant Defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression or death from any cause, whichever occurs first based on investigator's review.
Disease Control Rate up to 24 months after completion of study treatment of the last participant Defined as the proportion of participants in whom a confirmed CR or PR or stable disease (per RECIST 1.1, stable disease assessed at least 6 weeks after first dose) is observed as best overall response based on the investigator's review.
Time to Response up to 24 months after completion of study treatment of the last participant Defined as the time from randomization to first objective response (CR or PR per RECIST 1.1) based on the investigator's review.
Progression-Free Survival (PFS) up to 24 months after completion of study treatment of the last participant Based on the investigator's tumor assessment according to RECIST 1.1. Defined as the time from randomization to first confirmed objective tumor progression (progressive disease per RECIST 1.1), or death from any cause, whichever occurs first.
PFS rate up to 24 months after completion of study treatment of the last participant As measured at 6, 12, 18, and 24 months
Overall Survival (OS) up to 24 months after completion of study treatment of the last participant Defined as the time from randomization to death from any cause
OS rate up to 24 months after completion of study treatment of the last participant As measured at 6, 12, 18, and 24 months
Trial Locations
- Locations (65)
Peninsula Oncology Centre
🇦🇺Frankston, Australia
Hacettepe University Medical Faculty Oncology Hospital
🇹🇷Ankara, Turkey
Memorial Ankara Hospital
🇹🇷Ankara, Turkey
Liv Hospital
🇹🇷Ankara, Turkey
Ankara City Hospital
🇹🇷Ankara, Turkey
Gaziantep Sanko University Medical Faculty
🇹🇷Gaziantep, Turkey
Koc Universitesi Hastanesi (Koc University Hospital)
🇹🇷Istanbul, Turkey
Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi
🇹🇷Istanbul, Turkey
Acibadem Adana Hastanesi
🇹🇷Istanbul, Turkey
Yeditepe University Kosuyolu Hospital
🇹🇷Istanbul, Turkey
Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
🇹🇷Istanbul, Turkey
Medical Point Izmir Hospital
🇹🇷İzmir, Turkey
Kocaeli Universitesi Tip Fakultesi
🇹🇷Kocaeli, Turkey
Sakarya University - Faculty of Medicine
🇹🇷Sakarya, Turkey
Namik Kemal University Hospital
🇹🇷Tekirdağ, Turkey
Gazi University Medical Faculty
🇹🇷Yenimahalle, Turkey
Queen Elizabeth Hospital Birmingham - University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Velindre Hospital - Velindre NHS Trust
🇬🇧Cardiff, United Kingdom
Alaska Oncology and Hematology, LLC
🇺🇸Anchorage, Alaska, United States
Valkyrie Clinical Trials
🇺🇸Los Angeles, California, United States
Clermont Oncology Center
🇺🇸Clermont, Florida, United States
Hematology Oncology Associates of Treasure Coast
🇺🇸Port Saint Lucie, Florida, United States
Tallahassee Memorial Physician Partners - Cancer & Hematology Specialists
🇺🇸Tallahassee, Florida, United States
Carle Foundation Hospital d/b/a Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Fort Wayne Medical Oncology and Hematology, Inc
🇺🇸Fort Wayne, Indiana, United States
University of Kentucky Chandler Medical Center (UKCMC) - Markey Cancer Center (Lucille P. Markey Cancer Center)
🇺🇸Lexington, Kentucky, United States
Allina Health
🇺🇸Minneapolis, Minnesota, United States
Hattiesburg Clinic - Hattiesburg
🇺🇸Hattiesburg, Mississippi, United States
SSM Health Cancer Care - St. Clare
🇺🇸Fenton, Missouri, United States
Nebraska Hematology-Oncology (NHO) - Lincoln
🇺🇸Lincoln, Nebraska, United States
Clinical Research Alliance Inc
🇺🇸Westbury, New York, United States
Haywood Infusion Center
🇺🇸Clyde, North Carolina, United States
FirstHealth Outpatient Cancer Center
🇺🇸Pinehurst, North Carolina, United States
The Christ Hospital Cancer Center
🇺🇸Cincinnati, Ohio, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Millenium Research & Clinical Development
🇺🇸Houston, Texas, United States
SSM Health Cancer Care
🇺🇸Madison, Wisconsin, United States
Lyell McEwin Hospital
🇦🇺Adelaide, Australia
St. Vincent's Hospital
🇦🇺Fitzroy, Australia
Royal North Shore Hospital
🇦🇺St Leonards, Australia
Westmead Hospital
🇦🇺Westmead, Australia
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Yeungnam University Medical Center
🇰🇷Daegu, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Gyeongsang National University Hospital (GNUH)
🇰🇷Jinju-si, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Ajou University Hospital
🇰🇷Suwon-si, Korea, Republic of
Baskent University Hospital Adana Dr Turgut Noyan Research Center
🇹🇷Adana, Turkey
Medical Park Seyhan Hospital
🇹🇷Adana, Turkey
Adana City Training and Research Hospital
🇹🇷Adana, Turkey
Gulhane Egitim ve Arastirma Hastanesi
🇹🇷Ankara, Turkey
Ankara Etlik Sehir Hastanesi
🇹🇷Ankara, Turkey
Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital
🇹🇷Ankara, Turkey
Ninewells Hospital and Medical School - Tayside Health Board
🇬🇧Dundee, United Kingdom
Royal Devon and Exeter Hospital, Wonford - Royal Devon And Exeter NHS Foundation Trust
🇬🇧Exeter, United Kingdom
Huddersfield Royal Infirmary - Calderdale and Huddersfield NHS Foundation Trust
🇬🇧Huddersfield, United Kingdom
St James's University Hospital - Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
Sarah Cannon Research Institute
🇬🇧London, United Kingdom
Northern Centre for Cancer Care,The Newcastle Upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle Upon Tyne, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Royal Preston Hospital - Lancashire Teaching Hospitals NHS Foundation Trust
🇬🇧Preston, United Kingdom
Royal Stoke University Hospital - University Hospitals of North Midlands NHS Trust
🇬🇧Stoke-on-Trent, United Kingdom