Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT411

Inclusion Criteria:

For Part 1A:

• Histologically confirmed solid tumor (cytology was allowed for non-small cell lungcancer [NSCLC], small cell lung cancer [SCLC] and pancreatic cancer) that wasmetastatic or unresectable and for which there was no available standard therapylikely to confer clinical benefit, or patients who were not candidates for suchavailable therapy.

For Part 1B:

• Histologically or cytologically confirmed ES-SCLC (per the Veterans AdministrationLung Study Group [VALG] staging system) who received no prior chemotherapy forextensive stage disease.

• Those treated with prior chemo/radiotherapy with curative intent for limited-stagesmall cell lung cancer (LS-SCLC) were treatment-free for at least 6 months sincelast chemo/radiotherapy.

• Did not have interstitial lung disease or active, non-infectious pneumonitis.

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 understoodthe purpose of and procedures required for the trial and were willing to participatein 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:

1. International normalized ratio (INR) or prothrombin time <= 1.5 x upper limitnormal (ULN; unless on therapeutic anticoagulants with values withintherapeutic window),

2. Activated partial thromboplastin time (aPTT) <= 1.5 x ULN (unless ontherapeutic anticoagulants with values within therapeutic window).

• Adequate hematologic function at screening as determined by:

1. White blood cell count (WBC) >= 3 x 10^9/L,

2. Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (patient could not usegranulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colonystimulating 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.

• 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'ssyndrome),

2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 xULN; 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 m^2 - e.g., according to theabbreviated Modification of Diet in Renal Disease (MDRD) equation: GFR = 186 × (SCr^-1.154) × (age^-0.203) (where SCr, the serum creatinine level, was expressed inmg/dL; multiplied by 0.742 if the patient was female; multiplied by 1.212, if thepatient 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-humanchorionic gonadotropin [beta-hCG]) test/value at screening. Patients who werepostmenopausal or permanently sterilized were considered as not having reproductivepotential.

• WOCBP must have agreed not to donate eggs (ova, oocytes) for the purposes ofassisted reproduction during the entire trial, until 6 months after last BNT411treatment.

• A man who was sexually active with a WOCBP and had not had a vasectomy must haveagreed to use a barrier method of birth control, e.g., either condom withspermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragmor cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and allmen must also not donate sperm during the trial and for 6 months after receiving thelast dose of BNT411.

• All patients must have provided a Formalin Fixed Paraffin Embedded (FFPE) samplefrom the latest available archival tumor tissue. If such tissue was not provided,the sponsor's approval of enrollment was needed.

Exclusion Criteria:

Prior and Concomitant Therapy:

• Had received prior systemic therapy with a TLR7 agonist.

• Had been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents ortyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever was longer) ofthe start of trial treatment; immunotherapy/monoclonal antibodies within 3 weeks ofthe start of trial treatment; any live vaccine within 4 weeks of the start of trialtreatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6weeks of the start of trial treatment.

• Received concurrent systemic (oral or intravenous) steroid therapy >10 mg prednisonedaily 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.

• Had ongoing or active infection requiring intravenous treatment with anti-infectivetherapy that has been administered less than two weeks prior to first dose of trialtreatment.

• Had side effects of any prior therapy or procedures for any medical condition notrecovered to National Cancer Institute Common Terminology Criteria for AdverseEvents (NCI CTCAE) v.5 Grade <= 1.

• Notes: peripheral neuropathy Grade <= 2 was allowed; alopecia of any grade wasallowed.

Medical Conditions

• Evidence of new or growing brain or leptomeningeal metastases during screening.Patients with known brain or leptomeningeal metastases might have been eligible ifthey:

1. had radiotherapy, surgery or stereotactic surgery for the brain orleptomeningeal metastases,

2. have no neurological symptoms (excluding Grade ≤2 neuropathy),

3. have stable brain or leptomeningeal disease on the computed tomography (CT) ormagnetic resonance imaging (MRI) scan within 4 weeks before signing theinformed consent,

4. were not undergoing acute corticosteroid therapy or steroid taper.

• Notes: Patients with central nervous system symptoms had to undergo a CTscan or MRI of the brain to exclude new or progressive brain metastases.Spinal bone metastases were allowed, unless imminent fracture with cordcompression was anticipated.

• Had history of seizures other than isolated febrile seizure in childhood; had ahistory of a cerebrovascular accident or transient ischemic attack less than 6months 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 toinflammatory bowel disease, systemic lupus erythematosus (SLE), ankylosingspondylitis, scleroderma, or multiple sclerosis. Had any active immunologic disorderrequiring 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 orhypopituitarism, and euthyroid patients with a history of Grave's disease. Patientswith controlled hyperthyroidism must have been negative for thyroglobulin, thyroidperoxidase antibodies, and thyroid-stimulating immunoglobulin prior to trial drugadministration.

• 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 immunodeficiencysyndrome (AIDS)-defining opportunistic infections.

• Had known history/positive serology for hepatitis B requiring active anti-viraltherapy (unless immune due to vaccination or resolved natural infection or unlesspassive immunization due to immunoglobulin therapy). Patients with positive serologymust have had Hepatitis B virus (HBV) viral load below the limit of quantification.

• Active Hepatitis C virus (HCV) infection; patients who had completed curativeantiviral treatment with HCV viral load below the limit of quantification wereallowed.

• Notes: Country-specific criteria for Germany - To confirm that a patient wouldbe eligible, an active infection with HIV/Hepatitis B or C was ruled out byserum blood test at screening.

• Had a known hypersensitivity to a component of BNT411 drug product, or anothersimilar 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 asadequately treated carcinoma in situ of the cervix, basal or squamous cell skincancer, localized prostate cancer, or ductal carcinoma in situ).

Other Comorbidities

• Had abnormal electrocardiograms (ECGs) that were clinically significant, such asFramingham-corrected QT interval >480 ms.

• In the opinion of the treating investigator, had any concurrent conditions thatcould pose an undue medical hazard or interfere with the interpretation of the trialresults; these conditions included, but were 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 asymptomaticatrial fibrillation),

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.

• Had a cognitive, psychological or psychosocial impediment that would impair theability of the patient to receive therapy according to the protocol or adverselyaffect 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 USprescribing information (USPI) or summary of product characteristics (SmPC) in Part 1B.