Solid TumorPhase 1/2NCT04101357
Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT411
A Phase 1/2 study testing BNT411, Atezolizumab and Carboplatin in people with Solid Tumor and Extensive-stage Small Cell Lung Cancer, run by BioNTech SE at 12 sites in 4 countries.
Trial summary
This first-in-human (FIH) trial aimed to establish a safe dose of BNT411 as a monotherapy and in combination with atezolizumab, carboplatin and etoposide. BNT411 is a toll-like receptor 7 (TLR7) agonist which is expected to mount broad innate and adaptive immune reactions, especially in combination with cytotoxic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Extensive-stage Small Cell Lung Cancer
- What is being tested?
- BNT411, Atezolizumab and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 12 sitesin 4 countries
- Study dates
- 19 Jun 2020to 23 May 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For Part 1A:
- Histologically confirmed solid tumor (cytology was allowed for non-small cell lung cancer [NSCLC], small cell lung cancer [SCLC] and pancreatic cancer) that was metastatic or unresectable and for which there was no available standard therapy likely to confer clinical benefit, or patients who were not candidates for such available therapy.
- For Part 1B:
- Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system) who received no prior chemotherapy for extensive stage disease.
- Those treated with prior chemo/radiotherapy with curative intent for limited-stage small cell lung cancer (LS-SCLC) were treatment-free for at least 6 months since last chemo/radiotherapy.
- Did not have interstitial lung disease or active, non-infectious pneumonitis.
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- For Both Part 1A and Part 1B:
- Male and female >= 18 years of age.
- Must have signed an informed consent form (ICF) indicating that he or she understood the purpose of and procedures required for the trial and were willing to participate in the trial prior to any trial-related assessments or procedures.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Measurable disease according to RECIST 1.1.
- Albumin level at screening >= 30 g/L.
- Adequate coagulation function at screening as determined by:
- International normalized ratio (INR) or prothrombin time <= 1.5 x upper limit normal (ULN; unless on therapeutic anticoagulants with values within therapeutic window),
- Activated partial thromboplastin time (aPTT) <= 1.5 x ULN (unless on therapeutic anticoagulants with values within therapeutic window).
- Adequate hematologic function at screening as determined by:
- White blood cell count (WBC) >= 3 x 10^9/L,
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (patient could not use granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) to achieve these WBC and ANC levels),
- Platelet count >= 100 x 10^9/L,
- Hemoglobin (Hgb) >= 9.0 g/dL.
- Adequate hepatic function at screening as determined by:
- Total bilirubin <= 1.5 mg/dL (or <= 2.0 mg/dL for patients with known Gilbert's syndrome),
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 x ULN; or <= 5 x ULN in patients with metastatic liver disease.
- Adequate renal function at screening as determined by:
- Glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 - e.g., according to the abbreviated Modification of Diet in Renal Disease (MDRD) equation: GFR = 186 × (SCr^-1.154) × (age^-0.203) (where SCr, the serum creatinine level, was expressed in mg/dL; multiplied by 0.742 if the patient was female; multiplied by 1.212, if the patient was African-American (Levey et al., 1999).
- Were able to attend trial visits as required by the protocol.
- Women of childbearing potential (WOCBP) must have had a negative serum (beta-human chorionic gonadotropin [beta-hCG]) test/value at screening. Patients who were postmenopausal or permanently sterilized were considered as not having reproductive potential.
- WOCBP must have agreed not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial, until 6 months after last BNT411 treatment.
- A man who was sexually active with a WOCBP and had not had a vasectomy must have agreed to use a barrier method of birth control, e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the trial and for 6 months after receiving the last dose of BNT411.
- All patients must have provided a Formalin Fixed Paraffin Embedded (FFPE) sample from the latest available archival tumor tissue. If such tissue was not provided, the sponsor's approval of enrollment was needed.
Who cannot join
- Prior and Concomitant Therapy:
- Had received prior systemic therapy with a TLR7 agonist.
- Had been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever was longer) of the start of trial treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of trial treatment; any live vaccine within 4 weeks of the start of trial treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of trial treatment.
- Received concurrent systemic (oral or intravenous) steroid therapy >10 mg prednisone daily or its equivalent for an underlying condition.
- Received concurrent strong inhibitors or inducers of the cytochrome P450 enzymes.
- Had major surgery within the 4 weeks before the first dose of BNT411.
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- Had ongoing or active infection requiring intravenous treatment with anti-infective therapy that has been administered less than two weeks prior to first dose of trial treatment.
- Had side effects of any prior therapy or procedures for any medical condition not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5 Grade <= 1.
- Notes: peripheral neuropathy Grade <= 2 was allowed; alopecia of any grade was allowed.
- Medical Conditions
- Evidence of new or growing brain or leptomeningeal metastases during screening. Patients with known brain or leptomeningeal metastases might have been eligible if they:
- had radiotherapy, surgery or stereotactic surgery for the brain or leptomeningeal metastases,
- have no neurological symptoms (excluding Grade ≤2 neuropathy),
- have stable brain or leptomeningeal disease on the computed tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the informed consent,
- were not undergoing acute corticosteroid therapy or steroid taper.
- Notes: Patients with central nervous system symptoms had to undergo a CT scan or MRI of the brain to exclude new or progressive brain metastases. Spinal bone metastases were allowed, unless imminent fracture with cord compression was anticipated.
- Had history of seizures other than isolated febrile seizure in childhood; had a history of a cerebrovascular accident or transient ischemic attack less than 6 months ago.
- Had effusions (pleural, pericardial, or ascites) requiring drainage.
- Had eye pathology likely to confound observation of potential ocular adverse events.
- Had a fever >=38°C within 3 days before signing the ICF.
- Had a history of autoimmune disease active or past including but not limited to inflammatory bowel disease, systemic lupus erythematosus (SLE), ankylosing spondylitis, scleroderma, or multiple sclerosis. Had any active immunologic disorder requiring immunosuppression with steroids or other immunosuppressive agents (e.g., azathioprine, cyclosporine A) with the exception of patients with isolated vitiligo, resolved childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism, and euthyroid patients with a history of Grave's disease. Patients with controlled hyperthyroidism must have been negative for thyroglobulin, thyroid peroxidase antibodies, and thyroid-stimulating immunoglobulin prior to trial drug administration.
- Had known history of seropositivity for human immunodeficiency virus (HIV) with CD4+ T-cell (CD4+) counts <350 cells/µL and with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections.
- Had known history/positive serology for hepatitis B requiring active anti-viral therapy (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy). Patients with positive serology must have had Hepatitis B virus (HBV) viral load below the limit of quantification.
- Active Hepatitis C virus (HCV) infection; patients who had completed curative antiviral treatment with HCV viral load below the limit of quantification were allowed.
- Notes: Country-specific criteria for Germany - To confirm that a patient would be eligible, an active infection with HIV/Hepatitis B or C was ruled out by serum blood test at screening.
- Had a known hypersensitivity to a component of BNT411 drug product, or another similar compound.
- Had another primary malignancy that has not been in remission for at least 2 years, with the exception of those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ).
- Other Comorbidities
- Had abnormal electrocardiograms (ECGs) that were clinically significant, such as Framingham-corrected QT interval >480 ms.
- In the opinion of the treating investigator, had any concurrent conditions that could pose an undue medical hazard or interfere with the interpretation of the trial results; these conditions included, but were not limited to:
- ongoing or active infection requiring antibiotic/antiviral/antifungal therapy,
- concurrent congestive heart failure (New York Heart Association [NYHA] Functional Classification Class III or IV),
- concurrent unstable angina,
- concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial fibrillation),
- acute coronary syndrome within the previous 6 months,
- significant pulmonary disease (shortness of breath at rest or on mild exertion) for example due concurrent severe obstructive pulmonary disease.
- Had a cognitive, psychological or psychosocial impediment that would impair the ability of the patient to receive therapy according to the protocol or adversely affect the ability of the patient to comply with the informed consent process, protocol, or protocol-required visits and procedures.
- Was pregnant or breastfeeding.
- Had any contraindication to atezolizumab, carboplatin or etoposide as per US prescribing information (USPI) or summary of product characteristics (SmPC) in Part 1B.
Trial locations and contacts
12 sites in 4 countries.
12 sites in 4 countries
Spain4 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Clinica Universidad de Navarra
Madrid, 28022
START Madrid - CIOCC. Grupo Hospital de Madrid (HM) - Centro Integral Oncologico Clara Campal (CIOCC)
Madrid, 28050
Hospital Universitario La Fe de Valencia
Valencia, 46026
United States3 sites
Northwestern Medical Faculty Foundation
Chicago, Illinois, 60611
Prisma Health-Upstate Cancer Institute
Greenville, South Carolina, 29605
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Germany3 sites
Universitaetsklinikum Koeln - (Recruiting only for part 1B and part 2)
Cologne, 50937
University Medical Center Hamburg-Eppendorf - (Recruiting only for part 1B and part 2)
Hamburg, 20246
Universitaetsmedizin der Johannes Gutenberg Universitat Mainz KoeR - (Recruiting only for part 1B and part 2)
Mainz, 55131
United Kingdom2 sites
Edinburgh Cancer Research Centre
Edinburgh, EH4 2XU
Sarah Cannon Research Institute
London, W1G 6AD
About this study
Official title: Phase 1/2a, First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BNT411 as a Monotherapy in Patients With Solid Tumors and in Combination With Atezolizumab, Carboplatin and Etoposide in Patients With Chemotherapy-naïve Extensive-stage Small Cell Lung Cancer (ES-SCLC)
This first-in-human (FIH) trial aimed to establish a safe dose of BNT411 as a monotherapy and in combination with atezolizumab, carboplatin and etoposide. BNT411 is a toll-like receptor 7 (TLR7) agonist which is expected to mount broad innate and adaptive immune reactions, especially in combination with cytotoxic therapies and immune checkpoint inhibitors.
Read the detailed description
The first part (Part 1A) of this trial was a FIH, open-label, dose-escalation trial studying BNT411 monotherapy in patients with different types of malignant solid tumors in order to determine the safety profile of BNT411. The second part (Part 1B) aimed to determine further the safety profile of BNT411 in combination with atezolizumab, carboplatin and etoposide in patients with chemotherapy-naïve ES-SCLC. The third part (Part 2) was the expansion phase to explore BNT411 further as a monotherapy or in combination with atezolizumab, carboplatin and etoposide in select tumor indications. Different treatment schedules and other indications were planned to be explored in Part 2 of this trial, however, the sponsor decided not to continue with this part of this trial.
- Being tested
- BNT411, Atezolizumab, Carboplatin, Etoposide
- Keywords
- Solid Tumor, Extensive-stage Small Cell Lung Cancer
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BNT411Drug
intravenous
AtezolizumabDrug
intravenous
CarboplatinDrug
intravenous
EtoposideDrug
intravenous
| Study group | Role | What they receive |
|---|---|---|
| Part 1A - monotherapy dose escalation | Experimental | BNT411 monotherapy Receives: Drug: BNT411 |
| Part 1B - combination dose escalation | Experimental | BNT411 in combination with atezolizumab, carboplatin, and etoposide. Receives: Drug: BNT411; Drug: Atezolizumab; Drug: Carboplatin; Drug: Etoposide |
| Part 2 - expansion cohorts | Experimental | BNT411 either as monotherapy or in combination with atezolizumab, carboplatin, and etoposide. Please note that the sponsor decided not to continue with this part of this trial. Receives: Drug: BNT411; Drug: Atezolizumab; Drug: Carboplatin; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs)
DLTs were defined as any non-immune-related adverse events (AEs) or immune-related AEs during the first treatment cycle that was of Grade 3 and that did not resolve to Grade 1 or lower within a week, or that were of Grade 4. AEs were graded for severity using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0), where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4 - Life-threatening consequences; and Grade 5: Death related to AE.
Measured: Cycle 1 (21 Days)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs
A TEAE was defined as any AE with an onset date on or after the first administration of trial treatment (if AE was absent before the first administration of trial treatment) or worsened after the first administration of trial treatment (if AE was present before the first administration of trial treatment). AEs occurring more than 60 days after last treatment administration were considered as treatment-emergent only if assessed as related to the trial treatment by the investigator. Serious adverse event (SAE): any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect or was another medically important condition. AE were graded for severity using NCI-CTCAE v5.0, where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4 - Life-threatening consequences; and Grade 5: Death related to AE.
Measured: From Baseline until 60 days after last dose of study treatment (3 years and 11 months)
Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs
Participants with dose reduction and/or discontinuation of BNT411 due to TEAEs are reported.
Measured: From Baseline until 60 days after last dose of study treatment (3 years and 11 months)
Maximal Tolerated Dose (MTD) of BNT411
The MTD defined as the highest tolerated dose was reported based on the DLTs and TEAEs experienced by participants.
Measured: Cycle 1 (21 days)
Recommended Phase 2 Dose (RP2D) of BNT411
RP2D was based on integrated evaluation of safety, tolerability, clinical benefit, pharmacokinetic (PK), and pharmacodynamic data, for all dose levels was tested.
Measured: Cycle 1 (21 days)
Secondary outcomes (7)
Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last)
AUC0-last defined as the AUC from time 0 to the last measurable time-point was calculated from plasma concentrations of BNT411 using the linear-log trapezoidal method.
Measured: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
PK Assessment for BNT411: Clearance (CL)
Clearance reflects the elimination of the drug from the body was estimated from plasma concentrations of BNT411 as Dose/AUC0-inf. Dose was converted, as necessary, to reflect the amount of anhydrous BNT411 administered.
Measured: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
PK Assessment for BNT411: Volume of Distribution (Vd)
Volume of distribution (Vd) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vd was estimated from plasma concentrations of BNT411.
Measured: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
PK Assessment for BNT411: Maximum Plasma Concentration (Cmax)
Cmax defined as the maximum observed plasma concentration was estimated from plasma concentrations of BNT411.
Measured: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
PK Assessment for BNT411: Time to Reach Cmax (Tmax)
Tmax defined as the time to reach maximum (peak) concentration was estimated from plasma concentrations of BNT411.
Measured: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
PK Assessment for BNT411: Trough Concentration (Ctrough)
Ctrough defined as the pre-dose concentrations of BNT411 was estimated from the plasma concentrations of BNT411.
Measured: Part 1A: Start of infusion on Cycle 1 Day 8, Day 15, Day 22, Day 43; Day 85; Part 1B: Start of infusion on Cycle 1 Day 8, Day 15, Day 23, Day 44 (each cycle duration=21 days)
PK Assessment for BNT411: Terminal Elimination Half-life (T1/2)
Terminal elimination half-life was estimated from the plasma concentrations of BNT411.
Measured: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2019
- Study start19 Jun 2020
- Primary completion19 Jan 2024
- Study completion23 May 2024
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by BioNTech SEThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioNTech SE
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- BioNTech Responsible Person, Study director, BioNTech SE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04101357
- Sponsor's protocol ID
- BNT411-01
- Other IDs
- 2019-003593-17, 2019
- Status last verified
- Feb 2025
- First submitted
- 20 Sep 2019
- Last updated
- 18 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2a, First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BNT411 as a Monotherapy in Patients With Solid Tumors and in Combination With Atezolizumab, Carboplatin and Etoposide in Patients With Chemotherapy-naïve Extensive-stage Small Cell Lung Cancer (ES-SCLC)
- ClinicalTrials.gov ID
- NCT04101357
- Acronym / sponsor ID
- BNT411-01
- Keywords
- Solid Tumor, Extensive-stage Small Cell Lung Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 54 participants (actual)
- Lead sponsor
- BioNTech SEIndustry (pharma, biotech, devices)
- Study start
- 19 Jun 2020 (actual)
- Primary completion
- 19 Jan 2024 (actual)
- Study completion
- 23 May 2024 (actual)
- First posted
- 24 Sep 2019 (actual)
- Results
- Posted 18 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This first-in-human (FIH) trial aimed to establish a safe dose of BNT411 as a monotherapy and in combination with atezolizumab, carboplatin and etoposide. BNT411 is a toll-like receptor 7 (TLR7) agonist which is expected to mount broad innate and adaptive immune reactions, especially in combination with cytotoxic therapies and immune checkpoint inhibitors.
Detailed description
The first part (Part 1A) of this trial was a FIH, open-label, dose-escalation trial studying BNT411 monotherapy in patients with different types of malignant solid tumors in order to determine the safety profile of BNT411. The second part (Part 1B) aimed to determine further the safety profile of BNT411 in combination with atezolizumab, carboplatin and etoposide in patients with chemotherapy-naïve ES-SCLC. The third part (Part 2) was the expansion phase to explore BNT411 further as a monotherapy or in combination with atezolizumab, carboplatin and etoposide in select tumor indications. Different treatment schedules and other indications were planned to be explored in Part 2 of this trial, however, the sponsor decided not to continue with this part of this trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1A - monotherapy dose escalation | Experimental | Drug: BNT411BNT411 monotherapy |
| Part 1B - combination dose escalation | Experimental | Drug: BNT411, Drug: Atezolizumab, Drug: Carboplatin, Drug: EtoposideBNT411 in combination with atezolizumab, carboplatin, and etoposide. |
| Part 2 - expansion cohorts | Experimental | Drug: BNT411, Drug: Atezolizumab, Drug: Carboplatin, Drug: EtoposideBNT411 either as monotherapy or in combination with atezolizumab, carboplatin, and etoposide. Please note that the sponsor decided not to continue with this part of this trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Histologically confirmed solid tumor (cytology was allowed for non-small cell lung cancer [NSCLC], small cell lung cancer [SCLC] and pancreatic cancer) that was metastatic or unresectable and for which there was no available standard therapy likely to confer clinical benefit, or patients who were not candidates for such available therapy.
- Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system) who received no prior chemotherapy for extensive stage disease.
- Those treated with prior chemo/radiotherapy with curative intent for limited-stage small cell lung cancer (LS-SCLC) were treatment-free for at least 6 months since last chemo/radiotherapy.
- Did not have interstitial lung disease or active, non-infectious pneumonitis.
- Male and female >= 18 years of age.
Key exclusion criteria (39 listed)
- Had received prior systemic therapy with a TLR7 agonist.
- Had been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever was longer) of the start of trial treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of trial treatment; any live vaccine within 4 weeks of the start of trial treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of trial treatment.
- Received concurrent systemic (oral or intravenous) steroid therapy >10 mg prednisone daily or its equivalent for an underlying condition.
- Received concurrent strong inhibitors or inducers of the cytochrome P450 enzymes.
- Had major surgery within the 4 weeks before the first dose of BNT411.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BNT411intravenous | Drug | Part 1A - monotherapy dose escalation, Part 1B - combination dose escalation, Part 2 - expansion cohorts |
| Atezolizumabintravenous | Drug | Part 1B - combination dose escalation, Part 2 - expansion cohorts |
| Carboplatinintravenous | Drug | Part 1B - combination dose escalation, Part 2 - expansion cohorts |
| Etoposideintravenous | Drug | Part 1B - combination dose escalation, Part 2 - expansion cohorts |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Cycle 1 (21 Days)
DLTs were defined as any non-immune-related adverse events (AEs) or immune-related AEs during the first treatment cycle that was of Grade 3 and that did not resolve to Grade 1 or lower within a week, or that were of Grade 4. AEs were graded for severity using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0), where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4 - Life-threatening consequences; and Grade 5: Death related to AE.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs
Time frame: From Baseline until 60 days after last dose of study treatment (3 years and 11 months)
A TEAE was defined as any AE with an onset date on or after the first administration of trial treatment (if AE was absent before the first administration of trial treatment) or worsened after the first administration of trial treatment (if AE was present before the first administration of trial treatment). AEs occurring more than 60 days after last treatment administration were considered as treatment-emergent only if assessed as related to the trial treatment by the investigator. Serious adverse event (SAE): any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect or was another medically important condition. AE were graded for severity using NCI-CTCAE v5.0, where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4 - Life-threatening consequences; and Grade 5: Death related to AE.
Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs
Time frame: From Baseline until 60 days after last dose of study treatment (3 years and 11 months)
Participants with dose reduction and/or discontinuation of BNT411 due to TEAEs are reported.
Maximal Tolerated Dose (MTD) of BNT411
Time frame: Cycle 1 (21 days)
The MTD defined as the highest tolerated dose was reported based on the DLTs and TEAEs experienced by participants.
Recommended Phase 2 Dose (RP2D) of BNT411
Time frame: Cycle 1 (21 days)
RP2D was based on integrated evaluation of safety, tolerability, clinical benefit, pharmacokinetic (PK), and pharmacodynamic data, for all dose levels was tested.
7 secondary outcomes
Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last)
Time frame: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
PK Assessment for BNT411: Clearance (CL)
Time frame: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
PK Assessment for BNT411: Volume of Distribution (Vd)
Time frame: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
PK Assessment for BNT411: Maximum Plasma Concentration (Cmax)
Time frame: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
PK Assessment for BNT411: Time to Reach Cmax (Tmax)
Time frame: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
PK Assessment for BNT411: Trough Concentration (Ctrough)
Time frame: Part 1A: Start of infusion on Cycle 1 Day 8, Day 15, Day 22, Day 43; Day 85; Part 1B: Start of infusion on Cycle 1 Day 8, Day 15, Day 23, Day 44 (each cycle duration=21 days)
PK Assessment for BNT411: Terminal Elimination Half-life (T1/2)
Time frame: Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
BioNTech Responsible Person study director
BioNTech SE
12 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BNT411, Atezolizumab and Carboplatin in people with Solid Tumor and Extensive-stage Small Cell Lung Cancer, run by BioNTech SE at 12 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Spain, United States, Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Cycle 1 (21 Days)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2025.