Abstract CT051: Preliminary results from LuCa-MERIT-1, a first-in-human Phase I trial evaluating the fixed antigen mRNA vaccine BNT116 + docetaxel in patients with advanced non-small cell lung cancer
Authors: Öven Bala Başak , Baz David Vicente , Wolf Jürgen , Ates Ozturk , Göker Erdem , Brück Patrick , Wenger Michael , Munshi Neru , Tsyhankova Iryna , Tsyhankova Iryna , Kaczorowska Malgorzata , Schell Thomas , Markman Janet L. , Yang Huyuan , Türeci Özlem , Şahin Uğur , Forde Patrick , Atmaca Akin 
Published: April 2024

Abstract
Background: Non-small cell lung cancer (NSCLC) is often diagnosed late with many patients (pts) not responding to first line therapy or only responding for a limited time. BNT116 is an intravenously administered uridine RNA-based lipoplex cancer vaccine comprising six mRNAs (MAGE A3, CLDN6, KK-LC-1, PRAME, MAGE A4, MAGE C1), each encoding a tumor-associated antigen (TAA) frequently expressed in NSCLC. Here, we present preliminary results from pts with advanced unresectable or metastatic NSCLC (ECOG 0-1) receiving BNT116 + docetaxel (DTX).
Methods: LuCa-MERIT-1 (NCT: 05142189, EudraCT: 2021-004739-94) is a first-in-human, open label, Phase I trial to determine safety (dose limiting toxicities [DLTs]; treatment-emergent adverse events [TEAEs]) and clinical activity (RECIST v1.1) of BNT116 alone or in combinations. The cohort reported here will inform the dose of BNT116 in combination with DTX. Pts must have progressed on PD-1/PD-L1 inhibitor and a platinum-based chemotherapy. Biomarker analysis includes e.g., immunogenicity (ELISpot, n=3), cytokines (MSD, n=20), ctDNA (Avenio ctDNA Surveillance, n=~20), and PD-L1 (IHC, n=20).
Results: As of 01 DEC 2023, 20 pts (median age 66 years) have received BNT116 in addition to DTX at 75 mg/m2 Q3W. The combination demonstrated a manageable safety profile. All pts experienced at least one TEAE. TEAEs ≥Grade 3/4, (incidence rate ≥10%) include neutropenia (n=10 [50%]), pneumonia (n=3 [15%]), hypertension (n=3 [15%]), lymphocyte count decreased, diarrhea, and fatigue (each n=2 [10%]). Serious TEAEs were observed in ten pts (50%), of which three were considered as related to BNT116 (Grade 3 cytokine release syndrome, Grade 3 bronchospasm, and Grade 3 pyrexia) and three were considered as related to DTX (Grade 3 diarrhea, Grade 3 rash, and Grade 4 febrile neutropenia). No DLTs within the dose confirmation period or deaths under treatment were observed. Seven of 20 pts (35%) had a partial response, 10 of 20 pts (50%) had stable disease. The objective response rate was 35% (95% CI: 15.4-59.2) and the disease control rate was 85% (95% CI: 62.1-96.8). Robust antigen-specific T-cell responses and cytokine induction were observed even with the addition of DTX and the use of prophylactic dexamethasone on Day 2 of each cycle.
Conclusions: BNT116 + DTX shows encouraging antitumor activity, consistent induction of immune responses, a manageable safety profile, and no signs of additive toxicity. Updated safety and clinical activity data will be presented along with additional biomarker data.
(Funded by BioNTech)
Citation Format: Bala Başak Öven, David Vicente Baz, Jürgen Wolf, Ozturk Ates, Erdem Göker, Patrick Brück, Michael Wenger, Neru Munshi, Iryna Tsyhankova, Iryna Tsyhankova, Malgorzata Kaczorowska, Thomas Schell, Janet L. Markman, Huyuan Yang, Özlem Türeci, Uğur Şahin, Patrick Forde, Akin Atmaca. Preliminary results from LuCa-MERIT-1, a first-in-human Phase I trial evaluating the fixed antigen mRNA vaccine BNT116 + docetaxel in patients with advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT051.