LuCa-MERIT-1: First-in-human, Open Label, Phase I Dose Confirmation Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer
Summary
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.
Detailed description
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.
Arms & interventions
- BiologicalBNT116
Intravenous injection
- BiologicalCemiplimab
Intravenous infusion
- DrugDocetaxel
Intravenous infusion
- DrugCarboplatin
Intravenous infusion
- DrugPaclitaxel
Intravenous infusion
- BiologicalBNT316
Intravenous infusion
- Biologicalanti-B7-H3 antibody conjugated to topoisomerase I inhibitor
Intravenous infusion
- Biologicalanti-HER3 antibody conjugated to topoisomerase I inhibitor
Intravenous infusion
- BiologicalBispecific antibody for PD-L1 and VEGF-A
Intravenous infusion
- BiologicalOsimertinib
Oral
- BiologicalALK-inhibitor or RET-inhibitor
Oral
Outcome measures
Primary
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
Secondary
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Overall Response Rate (ORR)
Time frame: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Response (DoR)
Time frame: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Disease Control Rate (DCR)
Time frame: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Duration of Disease Control
Time frame: up to 27 months
Cohorts 1, 2, 3, 4, 7, 8, 9, and 10: Progression-Free Survival (PFS)
Time frame: up to 48 months
Cohorts EGFR (osimertinib): PFS
Time frame: up to 48 months
Cohort ALK/RET (ALK TKI or RET TKI): PFS
Time frame: up to 48 months
Cohorts EGFR and ALK/RET: (BNT116): PFS per molecular NSCLC subtype
Time frame: up to 48 months
Cohorts 1-11: Overall Survival (OS)
Time frame: up to 48 months
Cohorts 5, 6 and 11: Event Free Survival (EFS)
Time frame: up to 48 months
Cohort 6: Rate of Pathologic Responses
Time frame: At time of surgery (approximately after 3 months treatment)
Cohorts 5, 6 and 11: EFS Rate at 12 and 24 months
Time frame: up to 24 months
Cohort 6: ORR at the End of Neo-Adjuvant Treatment (Using RECIST v1.1)
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
Eligibility criteria
Study locations (5)
University of Kentucky Chandler Medical Center
Lexington, Kentucky, 40536
Norton Cancer Institute
Louisville, Kentucky, 40202
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
MD Anderson Cancer Center
Houston, Texas, 77030
NEXT Virginia
Fairfax, Virginia, 22031