This first-in-human (FIH) study for BNT116 aims to establish the safety profile and a safe dose for BNT116 monotherapy as well as for BNT116 in combination with approved medicinal products and/or in combination with investigational medicinal products (IMPs) including, but not limited to, cemiplimab, docetaxel, carboplatin, paclitaxel, osimertinib, anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), rearranged during transfection (RET) TKIs, BNT316 (an anti-cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\] antibody), an anti-B7-H3 antibody conjugated to a topoisomerase I inhibitor, an anti-human epidermal growth factor receptor 3 (HER3) antibody conjugated to a topoisomerase I inhibitor or a bispecific antibody for programmed death ligand 1 (PD-L1) and vascular endothelial growth factor A (VEGF-A) in participants with non-small cell lung cancer (NSCLC).
The study will comprise several cohorts for dose confirmation in monotherapy as well as in combinations of BNT116 as mentioned above.
The study will enroll participants with NSCLC in advanced or metastatic stage in Cohorts 1 to 4 and Cohorts 7 to 10, unresectable NSCLC Stage III in Cohorts 5 and 11, resectable NSCLC of Stage II and III in Cohort 6, advanced/metastatic epidermal growth factor receptor (EGFR)-mutant NSCLC in Cohort EGFR, and advanced/metastatic ALK rearranged or RET rearranged NSCLC in Cohort ALK/RET.
Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.
Participants must have histologically confirmed NSCLC and measurable disease by RECIST v1.1. Note: Participants in Cohorts 1, 5 and 11 as well as in Cohorts EGFR and ALK/RET do not have to present with measurable disease.
Participants must present with unresectable Stage III or metastatic Stage IV NSCLC by American Joint Commission on Cancer (AJCC) Cancer Staging Manual, Eighth Edition.
Participants in Cohorts 5 and 11 must present with unresectable Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition before receiving pre-study chemoradiotherapy.
Participants in Cohort 6 with the initial diagnosis of resectable Stage II and Stage III NSCLC by AJCC Cancer Staging Manual, Eighth Edition.
Ongoing active systemic treatment against NSCLC.
Presence of a driver mutation for which approved target therapies are available except if the participant is not a candidate for the respective targeted therapy. EXCEPT participants in Cohort EGFR and Cohort ALK/RET.
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: Participants 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.
had radiotherapy or another appropriate therapy for the brain or spinal metastases, AND
Sequential
BNT116
Biological/VaccineIntravenous injection
Cemiplimab
Biological/VaccineIntravenous infusion
Docetaxel
DrugIntravenous infusion
Carboplatin
DrugIntravenous infusion
Paclitaxel
DrugIntravenous infusion
BNT316
Biological/VaccineIntravenous infusion
anti-B7-H3 antibody conjugated to topoisomerase I inhibitor
Biological/VaccineIntravenous infusion
anti-HER3 antibody conjugated to topoisomerase I inhibitor
Biological/VaccineIntravenous infusion
Bispecific antibody for PD-L1 and VEGF-A
Biological/VaccineIntravenous infusion
Osimertinib
Biological/VaccineOral
ALK-inhibitor or RET-inhibitor
Biological/VaccineOral
14
Treatment groupsSee each treatment group below.
Cohorts 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, EGFR and ALK/RET: Occurrence of Dose-Limiting Toxicities (DLTs) During the DLT Observation Period
Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.
Cohorts 1 to 11, EGFR and ALK/RET: Occurrence of Treatment-Emergent Adverse Events (TEAEs) Reported by Relationship, Seriousness, and Grade
According to National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0). Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.
Cohort 6 only: Occurrence of Post-Surgical Adverse Events (AEs) Related to BNT116 and Cemiplimab
Cohort 6 only: Occurrence of Treatment-Related Delays to Surgery More Than 9 weeks Post the Last Dose of Neo-Adjuvant Treatment
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Overall Response Rate (ORR)
ORR defined as the number of participants with complete response (CR) or partial response (PR) as best overall response (BOR) according to response evaluation criteria in solid tumors (RECIST) v1.1 divided by the number of participants in the efficacy analysis set.
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Response (DoR)
DoR defined as the time from initial response until first objective tumor progression according to RECIST v1.1.
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Disease Control Rate (DCR)
DCR defined as the number of participants with CR or PR or stable disease (SD) as BOR according to RECIST v1.1 divided by the number of participants in the efficacy analysis set.
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Disease Control
Duration of disease control defined as the time from initial detection of stable disease or response until first objective tumor progression according to RECIST v1.1.
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