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 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 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 chemotherapy-naïve ES-SCLC (per the Veterans
Administration Lung Study Group [VALG] staging system).
- Treatment-free for at least 6 months since last chemo/radiotherapy, among those
treated (with curative intent) with prior chemo/radiotherapy for LS SCLC.
- Has no interstitial lung disease or active, non-infectious pneumonitis.
For Both Part 1A and Part 1B 5. Male and female ≥ 18 years of age. 6. 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.
7. ECOG performance status of 0 to 1. 8. Measurable disease according to RECIST 1.1. 9.
Able to receive the first administration of trial treatment within 42 days from the last
documented disease progression.
10. Adequate coagulation function at Screening as determined by:
a. International normalized ratio (INR) or prothrombin time ≤1.5 x upper limit normal (ULN;
unless on therapeutic anticoagulants with values within therapeutic window), b. Activated
partial thromboplastin time (aPTT) ≤1.5 x ULN (unless on therapeutic anticoagulants with
values within therapeutic window).
11. Adequate hematologic function at Screening as determined by:
a. White blood count (WBC) ≥3 x 109/L b. Absolute neutrophil count (ANC) ≥1.5 x 109/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) c. Platelet count ≥100 x 109/L d. Hemoglobin (Hgb) ≥9.0 g/dL (may not transfuse or
use erythropoietin to obtain this Hgb level).
12. Adequate hepatic function at Screening as determined by:
a. Total bilirubin ≤ 1.5 mg/dL (or ≤ 2.0 mg/dL for patients with known Gilbert's syndrome)
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ALT) ≤2.5 x ULN; or
≤5 x ULN in patients with metastatic liver disease 13. 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; multiply it by
0.742 if the patient is female; multiply it by 1.212, if the patient is African-American
(Levey et al., 1999).
14. Able to attend trial visits as required by the protocol. 15. 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 (Section
10.4) can be considered as not having reproductive potential.
16. 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.
17. 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 (refer Section 10.4 for information on effective contraceptive methods).
18. 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 approval of
enrollment is needed.
Prior and Concomitant Therapy:
- Has received prior systemic therapy with a TLR7 agonist
- Has received anti-cancer chemotherapy, molecular-targeted drugs, radiotherapy,
immunotherapy (e.g., vaccines, or cytokines), or investigational agents within the 28
days prior to the first dose of BNT411.
- 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 3A4
and 3A5 (e.g., CYP3A4, CYP3A5).
- Has had major surgery within the 4 weeks before the first dose of BNT411.
- Ongoing or active infection requiring intravenous treatment with anti-infective
therapy that has been administered less than two weeks prior to first dose of study
- Has side effects of any prior therapy or procedures for any medical condition not
recovered to NCI CTCAE v.5 grade ≤1.
Medical Conditions 8. Current evidence of new or growing brain or spinal metastases during
screening. Patients with known brain or spinal metastases may be eligible if they:
a. had radiotherapy, surgery or stereotactic surgery for the brain or spinal metastases, b.
have no neurological symptoms (excluding Grade ≤2 neuropathy), c. have stable brain or
spinal disease on the CT or MRI scan within 4 weeks before signing the informed consent, d.
must not be undergoing acute corticosteroid therapy or steroid taper. Chronic steroid
therapy is acceptable provided that the dose is stable for the last 14 days prior to
screening (≤ 10 mg prednisone daily or equivalent), f.e. spinal bone metastases are
allowed, unless imminent fracture or cord compression is anticipated.
Notes: Subjects with central nervous system symptoms should undergo a Computed Tomography
(CT) scan or Magnetic Resonance Imaging (MRI) of the brain to exclude new or progressive
9. 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 ago.
10. Has effusions (pleural, pericardial, or ascites) requiring drainage. 11. Has retinal
detachment, current/history of anterior/intermediate/posterior uveitis (including
Vogt-Koyanagi-Harada syndrome, , current keratitis, thyroid-associated orbitopathy,
idiopathic orbital inflammation, ischemic retinopathy (including glaucoma associated
retinopathy), retinal vascular disease (e.g retinal vein occlusion, retinal artery
occlusion), severe non-proliferative diabetic retinopathy (NPDR), proliferative diabetic
retinopathy (PDR), cataract (according to AREDS lens grading system >2) 12. Has a fever
≥38°C within 3 days before signing the ICF. 13. 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
14. 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.
15. 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). Patients with positive serology must have
Hepatitis B virus (HBV) viral load below the limit of quantification.
16. Active Hepatitis C virus (HCV) infection; patients who have completed curative
antiviral treatment with HCV viral load below the limit of quantification are allowed.
17. Has a known hypersensitivity to a component of BNT411 drug product, or another similar
18. 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) Note: should be discussed with
Medical Monitor in case of uncertainties.
Other Comorbidities 19. Has abnormal electrocardiograms (ECGs) that are clinically
significant, such as QT prolongation >480 ms.
20. 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.
21. 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.
22. Is pregnant or breastfeeding.