Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer

Eligibility Criteria

• * Patients must have histologically confirmed NSCLC and measurable disease by RECIST v1.1. Note: Patients in Cohort 1 and Cohort 5 do not have to present with measurable disease.
• 1. Patients must present with unresectable Stage III or metastatic Stage IV NSCLC by American Joint Commission on Cancer (AJCC) Cancer Staging Manual, Eighth Edition.
• 2. Patients in Cohort 5 must present with unresectable Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition before receiving pre-trial chemoradiotherapy.
• 3. Patients in Cohort 6 with the initial diagnosis of resectable Stage II and Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition.
• * Patients in Cohorts 2, 4, 5, and 6 must be able to tolerate (additional) anti-PD-1 therapy (i.e., did not permanently discontinue anti-programmed death protein 1 \[PD-1\] / programmed death ligand 1 \[PD-L1\] therapy due to toxicity).
• * Patients must have an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤1, except for patients in Cohorts 1, 4, and 5 who are eligible with an ECOG-PS of 0-2.
• * Ongoing active systemic treatment against NSCLC.
• * Presence of a driver mutation for which approved target therapies are available except if the patient is not a candidate for the respective targeted therapy.
• * Ongoing or recent evidence (within the last 5 years) of significant autoimmune disease that required treatment with systemic immunosuppressive treatments which may suggest risk for immune-related adverse events. Note: Patients with autoimmune-related hyperthyroidism, autoimmune-related hypothyroidism who are in remission, or on a stable dose of thyroid-replacement hormone, vitiligo, or psoriasis may be included.
• * Current evidence of new or growing brain or spinal metastases during screening. Patients with leptomeningeal disease are excluded. Patients with known brain or spinal metastases may be eligible for all Cohorts, except for Cohort 5 and 6, if they:
• * had radiotherapy or another appropriate therapy for the brain or spinal metastases, AND
• * have no neurological symptoms that can be attributed to the current brain lesions, AND
• * have stable brain or spinal disease on the computed tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the informed consent (confirmed by stable lesions on two scans at least 4 weeks apart), AND
• * do not require steroid therapy for the treatment of brain or spinal metastases within 14 d before the first dose of trial treatment. Note: Spinal bone metastases (i.e., of the vertebrae) are allowed, unless imminent fracture or cord compression is anticipated.
• * Systemic immune suppression:
• * Current use of chronic systemic steroid medication (≤5 mg/day prednisolone equivalent is allowed); patients using physiological replacement doses of prednisone for adrenal or pituitary insufficiency are eligible. Note: Steroid medication given for supportive or prophylactic reasons during CRT for patients in Cohort 5 needs to be tapered to ≤5 mg/day prednisolone equivalent at latest on the day before the trial treatment starts.
• * Other clinically relevant systemic immune suppression within the last 3 months before trial enrollment.
• * 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.
• * Prior splenectomy.
• * History/risk of interstitial lung disease or low baseline lung function (baseline pulse oximetry of less than 92% oxygen saturation \[SpO2\] without additional oxygen).