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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06449209




Registration number
NCT06449209
Ethics application status
Date submitted
3/06/2024
Date registered
7/06/2024

Titles & IDs
Public title
Safety, Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Small-cell Lung Cancer in Combination With Chemotherapy
Scientific title
A Phase II, Multi-site, Open-label, Parallel Group Trial of BNT327 in Combination With Chemotherapy for Participants With Untreated Extensive-stage Small-cell Lung Cancer and Participants With Previously Treated Small-cell Lung Cancer
Secondary ID [1] 0 0
BNT327-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Extensive-stage Small-cell Lung Cancer 0 0
Small-cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BNT327 Dose Level 1 (DL1)
Treatment: Drugs - BNT327 Dose Level 2 (DL2)
Treatment: Drugs - Etoposide
Treatment: Drugs - Carboplatin
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Topotecan

Experimental: Cohort 1 Arm 1 - BNT327 DL1 + carboplatin + etoposide - Participants with ES-SCLC without prior systemic anticancer therapy received in the ES setting

Experimental: Cohort 1 Arm 2 - BNT327 DL2 + carboplatin + etoposide - Participants with ES-SCLC without prior systemic anticancer therapy received in the ES setting

Experimental: Cohort 2 Arm 1 - BNT327 DL1 + paclitaxel - Participants with SCLC who have disease progression/relapse

Experimental: Cohort 2 Arm 2 - BNT327 DL2 + paclitaxel - Participants with SCLC who have disease progression/relapse

Experimental: Cohort 3 Arm 1 - BNT327 DL1 + topotecan - Participants with SCLC who have disease progression/relapse

Experimental: Cohort 3 Arm 2 - BNT327 DL2 + topotecan - Participants with SCLC who have disease progression/relapse


Treatment: Drugs: BNT327 Dose Level 1 (DL1)
Intravenous (IV) infusion

Treatment: Drugs: BNT327 Dose Level 2 (DL2)
IV infusion

Treatment: Drugs: Etoposide
IV infusion

Treatment: Drugs: Carboplatin
IV infusion

Treatment: Drugs: Paclitaxel
IV infusion

Treatment: Drugs: Topotecan
IV infusion or oral capsules
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
up to 100 days after the last dose of treatment
Primary outcome [2] 0 0
Occurrence of dose interruption, reduction, and discontinuation of study treatment due to TEAEs
Timepoint [2] 0 0
up to 100 days after the last dose of treatment
Primary outcome [3] 0 0
Objective Response Rate
Timepoint [3] 0 0
up to 24 months after completion of study treatment of the last participant
Primary outcome [4] 0 0
Best percentage change from baseline in the tumor size
Timepoint [4] 0 0
up to 24 months after completion of study treatment of the last participant
Primary outcome [5] 0 0
Proportion of participants who have achieved early tumor shrinkage
Timepoint [5] 0 0
up to 2 months after first dose of treatment
Secondary outcome [1] 0 0
PK assessment: Maximum concentration (Cmax) derived from serum concentration of investigational medicinal product (IMP)
Timepoint [1] 0 0
from pre-dose to 21 days after study treatment
Secondary outcome [2] 0 0
PK assessment: Area under the curve during the dosing interval (AUCtau) values derived from serum concentration of IMP
Timepoint [2] 0 0
from pre-dose to 21 days after study treatment
Secondary outcome [3] 0 0
Incidence of detectable BNT327 antidrug antibodies in serum
Timepoint [3] 0 0
from pre-dose to 100 days after last dose of study treatment
Secondary outcome [4] 0 0
Duration of Response
Timepoint [4] 0 0
up to 24 months after completion of study treatment of the last participant
Secondary outcome [5] 0 0
Disease Control Rate
Timepoint [5] 0 0
up to 24 months after completion of study treatment of the last participant
Secondary outcome [6] 0 0
Time to Response
Timepoint [6] 0 0
up to 24 months after completion of study treatment of the last participant
Secondary outcome [7] 0 0
Progression-Free Survival (PFS)
Timepoint [7] 0 0
up to 24 months after completion of study treatment of the last participant
Secondary outcome [8] 0 0
PFS rate
Timepoint [8] 0 0
up to 24 months after completion of study treatment of the last participant
Secondary outcome [9] 0 0
Overall Survival (OS)
Timepoint [9] 0 0
up to 24 months after completion of study treatment of the last participant
Secondary outcome [10] 0 0
OS rate
Timepoint [10] 0 0
up to 24 months after completion of study treatment of the last participant

Eligibility
Key inclusion criteria
Inclusion Criteria (applicable to all participants unless otherwise specified):

* 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:

* Total bilirubin =1.5 × upper limit of normal (ULN).
* With Gilbert's syndrome total bilirubin <3 mg/dL and direct bilirubin =ULN. Note, Gilbert's syndrome must be documented appropriately as past medical history.
* Participants without liver metastasis alanine aminotransferase and aspartate aminotransferase =2 × ULN.
* Participants with liver metastasis alanine aminotransferase and aspartate aminotransferase =5 × ULN.
* Albumin =3.0 g/dL.
* Renal function: Serum creatinine =1.5 × ULN or creatinine clearance =50 mL/min. Cockcroft-Gault formula.
* Qualitative urine protein =1+. If qualitative urine protein =2+, a 24-hour urine protein quantitative test is required. If the 24-hour urine protein result is <1 g, the participant can be enrolled.
* Coagulation function: International normalized ratio or prothrombin time and activated partial thromboplastin time =1.5 × ULN unless the participant is receiving anticoagulation therapy as long as prothrombin or activated partial thromboplastin is within therapeutic range of intended use of anticoagulant.
* Are women of childbearing potential (WOCBP) who have a negative serum beta-human chorionic gonadotropin test at screening and before each IMP dose. Women born female that are postmenopausal (defined as 12 months with no menses without an alternative medical cause) or permanently sterilized (verified by medical records) will not be considered WOCBP and therefore will not be required to undergo pregnancy testing.
* Are WOCBP who agree to practice a highly effective form of contraception and to require their male sexual partners to use barrier contraception methods (preferably condoms), starting at Screening and continuously until 6 months after receiving the last study treatment.
* Are men who are sexually active with a partner born female and have not had a vasectomy who agree to use condoms and to ask their sexual partners to practice a highly effective form of contraception during the study, starting at the Screening Period and continuously until 6 months after receiving the last dose of IMP.
* Are WOCBP who agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study, starting at the Screening Period and continuously 6 months after receiving the last dose of IMP.
* Are men who are willing to refrain from sperm donation, starting at the Screening Period and continuously until 6 months after the last dose of IMP.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria (applicable to all participants):

* 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).
* Participants who received treatment for central nervous system metastases are not neurologically stable or still on steroids 10 days before initiating IMP of this study.
* Participants with known leptomeningeal metastases.
* Have active autoimmune disease or history of autoimmune diseases with anticipated relapse (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for those with clinically stable autoimmune thyroid disease or type 1 diabetes.
* Have had other malignant tumors within 2 years prior to the study treatment are not allowed. Except for those: who have been cured with local treatment (such as basal cell or squamous cell carcinoma of the skin, superficial or non-invasive bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, papillary carcinoma of thyroid and early stage prostate cancer).
* Have any of the following heart conditions within 6 months prior to the study treatment:

* Acute coronary syndrome, coronary artery bypass grafting, congestive heart failure, aortic dissection, stroke, or other Grade 3 and above cardiovascular and cerebrovascular events.
* New York Heart Association functional classification =II heart failure or left ventricular ejection fraction <50%.
* Those who have ventricular arrhythmias requiring clinical intervention, second- to third-degree atrioventricular block, or congenital long QT syndrome. Participants with treated cardiac arrythmia/atrial fibrillation are allowed.
* Mean QT interval corrected by Fridericia's method >480 ms (the electrocardiogram can be repeated at the discretion of the investigator).
* Use of cardiac pacemaker.
* Cardiac troponin I or T >2 x ULN.
* Have any of the following hypertension or diabetic conditions prior to initiation of study treatment:

* Uncontrolled hypertension (systolic blood pressure =160 mmHg and/or diastolic blood pressure =100 mmHg) while on antihypertensive medicine.
* Those with a history of hypertensive crisis or hypertensive encephalopathy.
* Poorly controlled diabetes (fasting blood glucose =13.3 mmol/L [240 mg/dL]).
* Have serious non-healing wounds, ulcers, or bone fractures. This includes history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess for which an interval of 6 months must pass before enrollment into this study. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation.
* Participants with evidence of major coagulation disorders or other significant risks of hemorrhage such as:

* History of intracranial or intraspinal hemorrhage.
* Tumor lesions invading large vessels and with significant risk of bleeding
* Had clinically significant hemoptysis or tumor hemorrhage within 1 month prior to the initiation of study treatment.
* Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters (e.g., PleurX) are allowed. However, participants who are clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis or with indwelling catheters, e.g., PleurX) are allowed.
* Participants with a history of serious Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior immunotherapy. Participants with a history of Grade =3 irAEs that did not lead to discontinuation of a prior immunotherapy but fully recovered may be enrolled per investigator's discretion. The investigator may request sponsor guidance in such cases.
* Have a known or suspected hypersensitivity to the study treatments including any active ingredient or excipients thereof.
* Have known human immunodeficiency virus infection or known acquired immunodeficiency syndrome, with the following exceptions:

* Participants with cluster of differentiation 4 (CD4)+ T-cell (CD4+) counts =350 cells/µL per local laboratory should generally be eligible for the study.
* Participants who have not had an opportunistic infection within the past 12 months.
* Have a known history/positive serology for hepatitis B requiring active antiviral therapy (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy). Individuals with positive serology must have hepatitis B virus viral load below the limit of quantification.
* Have an active hepatitis C virus infection; individuals who have completed curative antiviral treatment with hepatitis C virus viral load below the limit of quantification are allowed.
* Participants with AEs from prior antitumor therapy whose AE(s) have not returned to Grade 1 (graded by NCI CTCAE v5.0 criteria) or below (unless the investigator determines that certain AEs pose no safety risk to participants, such as hair loss, Grade 2 peripheral neuropathy or stable hypothyroidism under hormone replacement therapy) are not eligible for the study.
* Have superior vena cava syndrome or symptoms of spinal cord compression.
* Those with active, or a history of, pneumonitis requiring treatment with steroids, or has active, or a history of, interstitial lung disease. Those with a history of pulmonary fibrosis, or currently diagnosed with severe lung diseases such as interstitial pneumonia, pneumoconiosis, chemical pneumonitis, or any other condition resulting in significant impairment in lung function. Exception: Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable.
* Have active tuberculosis.
* Have underlying condition(s) that may increase the risk of the combination treatment or complicate the interpretation of AEs, as judged by the investigator, or other scenarios in which the investigator consider the participant as not eligible for the study.
* Are vulnerable individuals, i.e., are individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. This includes all sponsor, study site, or third party (e.g., contract research organization, vendor) personnel directly involved in the conduct of the sudy and their family members or dependents, as well as all study site personnel otherwise supervised by the investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2026
Actual
Sample size
Target
110
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Lyell McEwin Hospital - Adelaide
Recruitment hospital [2] 0 0
St. Vincent's Hospital - Fitzroy
Recruitment hospital [3] 0 0
Peninsula Oncology Centre - Frankston
Recruitment hospital [4] 0 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 0 0
5112 - Adelaide
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alaska
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Mississippi
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Wisconsin
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Cheongju-si
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Daegu
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Goyang-si
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Incheon
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Jinju-si
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Suwon-si
Country [20] 0 0
Turkey
State/province [20] 0 0
Ankara
Country [21] 0 0
Turkey
State/province [21] 0 0
Istanbul
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Birmingham
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Cardiff
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Dundee
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Exeter
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Guildford
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Huddersfield
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Leeds
Country [29] 0 0
United Kingdom
State/province [29] 0 0
London
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Newcastle Upon Tyne
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Nottingham
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Preston
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Stoke-on-Trent

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BioNTech SE
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
BioNTech Responsible Person
Address 0 0
BioNTech SE
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BioNTech clinical trials patient information
Address 0 0
Country 0 0
Phone 0 0
+49 6131 9084
Fax 0 0
Email 0 0
patients@biontech.de
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06449209