Trial purpose
Cancer treatment
Tumor type
Lung cancer
Age
18+
Clinical summary
Summary
This study has three cohorts which eligible participants will be assigned to based on their diagnosis and treatment history. Within each cohort, there are two treatment arms.
Cohort 1- Individuals with untreated extended-stage small-cell lung cancer (ES-SCLC)
- Arm 1 will receive BNT327 DL1 + Alkylating Agent + Topoisomerase Inhibitor A chemotherapy
- Arm 2 will receive BNT327 DL2 + Alkylating agent + Topoisomerase Inhibitor A chemotherapy
Cohorts 2 and 3 will enrol people with small-cell lung cancer who have progressed on either first- or -second-line treatment. Assignment to either Cohort 2 or 3 will be determine by the Investigator.
Cohort 2
- Arm 1 will receive BNT327 DL1 + Taxane chemotherapy
- Arm 2 will receive BNT327 DL2 + Taxane chemotherapy
Cohort 3
- Arm 1: BNT327 DL1 + Topoisomerase Inhibitor B chemotherapy
- Arm 2: BNT327 DL2 + Topoisomerase Inhibitor B chemotherapy
All treatments will be given as an intravenous (IV) infusion, except for Topoisomerase Inhibitor B which may be given as either an IV infusion or oral capsule.
Conditions
This trial is treating people with small-cell lung cancer
Eligibility
Exclusion
- Are pregnant or breastfeeding or are planning pregnancy or planning to father children during the study or within 60 days or five half-lives if known (whichever is longer) 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.
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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.
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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).
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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 N >2 x ULN.
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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.
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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 or higher irAEs that did not lead to treatment discontinuation of a prior immunotherapy should be discussed with the sponsor.
- Have a known or suspected hypersensitivity to the study treatments including any active ingredient or excipients thereof.
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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 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.
Inclusion
- You have had treatment, but your cancer has come back (relapsed or recurrent).
- Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
- You have been diagnosed with cancer, but have not received any treatment.
- You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
Exclusion
- You have been diagnosed with a prior or secondary type of cancer.
- You have certain types of non-cancer medical conditions.
- You have had certain treatments, surgical procedures or drugs.
Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.
More information
Trial Identifiers
Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:
Trial sponsor
BioNTech SE
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
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