Abstract 1196TiP
Background
Lung cancer is the leading cause of cancer deaths worldwide. The diagnosis of non-small cell lung cancer is often made when the disease is already advanced or metastatic (Stage IIIB/IV). The approved PD-1/PD-L1 inhibitors have demonstrated substantial anti-tumor activity, however, a majority of patients do not respond to therapy or only respond for a limited time. BNT116 is an intravenously (IV) administered cancer immunotherapy consisting of a mixture of six liposomally formulated RNAs each of which encodes for a different tumor-associated antigen. BNT116 alone or in combination with either docetaxel or the PD-1 inhibitor cemiplimab (Libtayo®) may have synergistic anti-tumor effects, thus potentially addressing the unmet medical need of these cancer patients.
Trial design
The trial comprises four cohorts, each with a single-step dose confirmation using a 3+3 design in both monotherapy and in combinations followed by an expansion phase including up to 20 patients in each cohort. Depending on the cohort, patients with measurable disease confirmed by RECIST 1.1 and the ability to tolerate additional PD-1 inhibitor therapy are included. In all cohorts, the first dose of BNT116 is given at 60 μg total RNA (C1D1). All subsequent doses of 90 μg total RNA are given once weekly for the initial 7 weeks followed by every 3-week (Q3W) dosing on Day 1 of each cycle. Cemiplimab (350 mg) may be added at the discretion of the investigator in cohort 1 after the second cycle. Patients in cohort 2 and 4 receive cemiplimab starting with cycle 1 day 1. Docetaxel will be administered at the approved dose of 75 mg/m2 IV Q3W on Day 2 of each cycle (Cohort 3). Primary endpoints are occurrence of dose limiting toxicities and adverse events coded using MedDRA® assessed according to NCI-CTCAE v5.0. Secondary endpoints are related to clinical activity, i.e., tumor assessments, as per RECIST 1.1. The first patient is planned to be dosed in May 2022, with enrolment expected for approximately 12 months.
Clinical trial identification
EudraCT: 2021-004739-94, NCT05142189.
Editorial acknowledgement
Legal entity responsible for the study
BioNTech SE.
Funding
BioNTech SE.
Disclosure
P.M. Forde: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Daiichi, F-Star, G1, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface; Other, Personal, Other, Trial Steering Committee membership: AstraZeneca; Non-Financial Interests, Personal, Member of the Board of Directors, and Scientific Advisory Board Member: LUNGevity; Other, Personal, Other, rial Steering Committee membership: BMS, Corvus; Financial Interests, Institutional, Research Grant: AstraZeneca, BioNTech, BMS, Corvus, Kyowa, Novartis, Regeneron. P. Brück: Financial Interests, Personal, Stocks/Shares: BioNTech SE; Financial Interests, Personal, Full or part-time Employment: BioNTech SE. N. Munshi: Financial Interests, Personal, Full or part-time Employment: BioNTech US. M.A. Kaczorowska, T. Schell: Financial Interests, Personal, Full or part-time Employment: BioNTech SE. Ö. Türeci, U. Sahin: Financial Interests, Personal, Member of the Board of Directors: BioNTech SE; Financial Interests, Personal, Stocks/Shares: BioNTech SE. All other authors have declared no conflicts of interest.