This first-in-human (FIH) trial aims 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.
For Part 1A:
- Histologically confirmed solid tumor (cytology is allowed for NSCLC, SCLC and
pancreatic cancer) that is metastatic or unresectable and for which there is no
available standard therapy likely to confer clinical benefit, or patients who are 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 LS-SCLC should be
treatment-free for at least 6 months since last chemo/radiotherapy.
- Has no interstitial lung disease or active, non-infectious pneumonitis.
For Both Part 1A and Part 1B
- Male and female ≥ 18 years of age.
- Must sign an informed consent form (ICF) indicating that he or she understands the
purpose of and procedures required for the trial and are willing to participate in the
trial prior to any trial related assessments or procedures.
- ECOG performance status of 0 to 1.
- Measurable disease according to RECIST 1.1.
- Albumin level at screening ≥30 g/L.
- Able to receive the first administration of trial treatment within 42 days from the
last documented disease progression.
- Adequate coagulation function at Screening as determined by:
1. International normalized ratio (INR) or prothrombin time ≤1.5 x upper limit
normal (ULN; unless on therapeutic anticoagulants with values within therapeutic
2. 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:
1. White blood count (WBC) ≥3 x 10^9/L
2. Absolute neutrophil count (ANC) ≥1.5 x 10^9/L (patient may not use
granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony
stimulating factor (GM-CSF) to achieve these WBC and ANC levels),
3. Platelet count ≥100 x 10^9/L,
4. Hemoglobin (Hgb) ≥9.0 g/dL (may not transfuse or use erythropoietin to obtain
this Hgb level).
- Adequate hepatic function at Screening as determined by:
1. Total bilirubin ≤ 1.5 mg/dL (or ≤ 2.0 mg/dL for patients with known Gilbert's
2. 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:
a. Glomerular filtration rate (GFR) ≥60 mL/min/1.73 m²- 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, is expressed in
mg/dL; multiplied by 0.742 if the patient is female; multiplied by 1.212, if the
patient is African-American (Levey et al., 1999).
- Able to attend trial visits as required by the protocol.
- Women of childbearing potential (WOCBP) must have a negative serum (beta-human
chorionic gonadotropin [beta-hCG]) test/value at Screening. Patients who are
postmenopausal or permanently sterilized can be considered as not having reproductive
- WOCBP must agree 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 is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree 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 provide an FFPE (Formalin Fixed Paraffin Embedded) from the latest
available archival tumor tissue. If such tissue cannot be provided, the sponsor's
approval of enrollment is needed.
Prior and Concomitant Therapy:
- Has received prior systemic therapy with a TLR7 agonist.
- Has been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or
tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever is 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.
- Receives concurrent systemic (oral or intravenous) steroid therapy >10 mg prednisone
daily or its equivalent for an underlying condition.
- Receives concurrent strong inhibitors or inducers of the cytochrome P450 enzymes.
- Has had major surgery within the 4 weeks before the first dose of BNT411.
- Has 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
- Has side effects of any prior therapy or procedures for any medical condition not
recovered to NCI CTCAE v.5 grade ≤1.
- Has any contraindication to atezolizumab, carboplatin or etoposide as per USPI or SmPC
in Part 1B.
- Current evidence of new or growing brain or leptomeningeal metastases during
screening. Patients with known brain or leptomeningeal metastases may be eligible if
1. had radiotherapy, surgery or stereotactic surgery for the brain or leptomeningeal
2. have no neurological symptoms (excluding Grade ≤2 neuropathy),
3. have stable brain or leptomeningeal disease on the CT or MRI scan within 4 weeks
before signing the informed consent,
4. are not undergoing acute corticosteroid therapy or steroid taper.
- Has history of seizures other than isolated febrile seizure in childhood; has a
history of a cerebrovascular accident or transient ischemic attack less than 6 months
- Has effusions (pleural, pericardial, or ascites) requiring drainage.
- Has eye pathology likely to confound observation of potential ocular AEs.
- Has a fever ≥38°C within 3 days before signing the ICF.
- Has 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. Has 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 be negative for thyroglobulin, thyroid peroxidase
antibodies, and thyroid-stimulating immunoglobulin prior to trial drug administration.
- Known history of seropositivity for human immunodeficiency virus (HIV) with CD4+
T-cell (CD4+) counts <350 cells/uL and with a history of acquired immunodeficiency
syndrome (AIDS)-defining opportunistic infections.
- 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
Hepatitis B virus (HBV) viral load below the limit of quantification.
- Active Hepatitis C virus (HCV) infection; patients who have completed curative
antiviral treatment with HCV viral load below the limit of quantification are allowed.
- Has a known hypersensitivity to a component of BNT411 drug product, or another similar
- Has 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).
- Has abnormal electrocardiograms (ECGs) that are clinically significant, such as
Framingham-corrected QT interval >480 ms.
- In the opinion of the treating investigator, has any concurrent conditions that could
pose an undue medical hazard or interfere with the interpretation of the trial
results; these conditions include, but are not limited to:
1. ongoing or active infection requiring antibiotic/antiviral/antifungal therapy,
2. concurrent congestive heart failure (New York Heart Association [NYHA] Functional
Classification Class III or IV),
3. concurrent unstable angina,
4. concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial
5. acute coronary syndrome within the previous 6 months,
6. significant pulmonary disease (shortness of breath at rest or on mild exertion)
for example due concurrent severe obstructive pulmonary disease.
- Has 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.
- Is pregnant or breastfeeding.