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.
The maximum duration of treatment for each individual participant in this study is: * Cohorts 1 to 4, Cohorts 7 to 10, Cohort EGFR, and Cohort ALK/RET: 24 months. * Cohorts 5 and 11: 18 cycles, i.e., 12 months. * Cohort 6: 4 cycles of neo-adjuvant treatment and 18 cycles of adjuvant treatment, i.e., 12 months of adjuvant treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
320
Intravenous injection
Intravenous infusion
Intravenous infusion
Intravenous infusion
Intravenous infusion
Intravenous infusion
Intravenous infusion
Intravenous infusion
Intravenous infusion
Oral
Oral
University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States
RECRUITINGNorton Cancer Institute
Louisville, Kentucky, United States
RECRUITINGJohns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
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.
Time frame: From first dose of IMP up to 21 days
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.
Time frame: up to 27 months
Cohort 6 only: Occurrence of Post-Surgical Adverse Events (AEs) Related to BNT116 and Cemiplimab
Time frame: up to 27 months
Cohort 6 only: Occurrence of Treatment-Related Delays to Surgery More Than 9 weeks Post the Last Dose of Neo-Adjuvant Treatment
Time frame: up to 6 months
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.
Time frame: up to 27 months
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.
Time frame: up to 27 months
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.
Time frame: up to 27 months
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.
Time frame: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Progression-Free Survival (PFS)
PFS defined as the time of first study treatment until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first.
Time frame: up to 48 months
Cohorts EGFR (osimertinib): PFS
Defined as the time of first treatment with osimertinib until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first. Cohort EGFR will enroll only at selected sites in the US.
Time frame: up to 48 months
Cohort ALK/RET (ALK TKI or RET TKI): PFS
Defined as the time of first treatment with a ALK TKI or RET TKI until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first. Cohort ALK/RET will enroll only at selected sites in the US.
Time frame: up to 48 months
Cohorts EGFR and ALK/RET: (BNT116): PFS per molecular NSCLC subtype
Defined as the time of first treatment with BNT116 until the first objective tumor progression according to RECIST v1.1 or death from any cause, whichever occurs first. Cohort EGFR and Cohort ALK/RET will enroll only at selected sites in the US.
Time frame: up to 48 months
Cohorts 1-11: Overall Survival (OS)
OS defined as the time of first study treatment until death from any cause.
Time frame: up to 48 months
Cohorts 5, 6 and 11: Event Free Survival (EFS)
EFS defined as the length of time from first study treatment to any of the following events: progression of disease, recurrence of disease or death from any cause, whichever occurs first.
Time frame: up to 48 months
Cohort 6: Rate of Pathologic Responses
Rate of pathologic responses defined as the number of participants with major or complete pathologic response in the surgical specimen from surgery after neo-adjuvant study treatment divided by the number of participants in the efficacy analysis set.
Time frame: At time of surgery (approximately after 3 months treatment)
Cohorts 5, 6 and 11: EFS Rate at 12 and 24 months
EFS rate defined as the number of participants without an EFS-defining event divided by the number of participants in the efficacy analysis set.
Time frame: up to 24 months
Cohort 6: ORR at the End of Neo-Adjuvant Treatment (Using RECIST v1.1)
ORR defined as the number of participants with CR or PR as BOR according to RECIST v1.1 divided by the number of participants in the efficacy analysis set.
Time frame: up to 3 months
Cohort 6: Rate of Progressive Disease at the End of Neo-Adjuvant Treatment (Using RECIST v1.1)
Time frame: up to 3 months
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NEXT Virginia
Fairfax, Virginia, United States
RECRUITINGScientia Clinical Research
Randwick, New South Wales, Australia
RECRUITINGRoyal North Shore Hospital
Sydney, New South Wales, Australia
RECRUITINGCancer Research SA
Adelaide, South Australia, Australia
RECRUITINGMonash Health
Clayton, Victoria, Australia
RECRUITINGUniversitätsklinikum Köln
Cologne, Germany
RECRUITING...and 34 more locations