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

• Status: Not yet recruiting
• Trial end date: 2027-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This First-in-human (FIH) trial for BNT116 aims to establish the safety profile and a safe dose for BNT116 monotherapy as well as for BNT116 in combination with cemiplimab or in combination with docetaxel in patients with advanced or metastasized non-small cell lung cancer (NSCLC). The trial will comprise several cohorts for dose confirmation in monotherapy as well as in combinations.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: BioNTech SE
• Treatments: Cemiplimab; Docetaxel

Criteria

Key Inclusion Criteria:

• Patients must have histologically confirmed unresectable Stage III or metastatic Stage IV NSCLC and measurable disease by RECIST v1.1. Note: Patients in Cohort 1 do not have to have measurable disease.

• Patients in Cohorts 2 and 4 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) and must have recovered to stage 1 or 0 from any previous PD-1/PD-L1-related toxicity or be on a stable hormone substitute therapy.

• Patients in Cohorts 2 and 3 must have an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤1. Patients in Cohort 1 and 4 with an ECOG-PS of 0-2 are eligible.

Cohort-specific inclusion criteria:

Cohort 1:

• Patients' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen as well as one other line of systemic therapy (except if a patient is not candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor and/or another line of systemic therapy).

Cohort 2:

• Patients must present with PD-L1 expression of tumor proportion score (TPS) ≥50% in tumor cells (as determined locally prior to inclusion in this trial).

• Patients must present with progressive disease either

1. in the advanced or metastasized stage of NSCLC: while on a PD-1/PD-L1 inhibitor therapy or within 6 months of termination of this treatment as first-line treatment. Or

2. be refractory to ongoing adjuvant therapy with a PD-1/PD-L1 inhibitor that has been given for at least 3 months in monotherapy (i.e., after an initial combination therapy) before being enrolled into this trial.

Cohort 3:

• Patients' prior therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen (except if a patient is not candidate for a platinum-based chemotherapy and/or PD-1/PD-L1 inhibitor).

Cohort 4:

• Patients' who are not candidates for chemotherapy as first-line treatment for the advanced or metastasized stage of NSCLC may be enrolled if presenting with PD-L1 expression: TPS ≥1% in tumor cells.

Key Exclusion Criteria:

• Ongoing active systemic treatment against NSCLC.

• Presence of a driver mutation for which approved target therapies are available.

• 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 if they:

• had radiotherapy or another appropriate therapy for the brain or spinal bone 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.

• 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.