Abstract 1085P
Background
MAGE-C2 (MC2) is an immunogenic cancer germline antigen that is highly expressed in melanoma, but not in normal tissues. For adoptive T cell therapy, we selected a highly specific T cell receptor (TCR) and developed a method to generate young MC2 TCR T cells. The primary objective of this first-in-human phase I trial is to determine the recommended phase II dose and demonstrate the safety and feasibility of treatment with autologous MC2 TCR T cells. Secondary objectives include treatment efficacy and measurements of MC2 TCR T cells as well as immune parameters in blood and tumor tissue.
Methods
This is an investigator-initiated single center clinical trial with accelerated titration of five dose levels up to 5.0x1010 MC2 TCR T cells. Patients with advanced melanoma are eligible if they have progressive disease after standard treatment, an HLA-A2 genotype and MC2-positive tumors. Prior to infusion of T cells, obtained by leukapheresis and processed into advanced therapeutic medicinal products (ATMPs), patients are treated with the epigenetic drugs valproic acid and 5-azacitine. Infusion of MC2 TCR T cells is supported by administration of low dose IL-2. Adverse events (AEs) are documented according to CTCAE v5.0, and tumor response is evaluated according to RECIST v1.1.
Results
So far, six eligible patients with uveal (n=3) and mucosal (n=3) melanoma have been treated. T cell ATMPs were successfully produced for the first four doses (5x107, 5x108, 5x109 and 1x1010 MC2 TCR T cells), and two T cell ATMPs were exceptionally released for a lower dose, enabling optimization of the production protocol. Up to the highest administered dose, no irreversible grade 3 or 4 AEs were observed. A mixed tumor response was observed at the second dose level. For higher dose levels, response evaluation is awaited. MC2 TCR T cells could be detected in blood up to six months post infusion.
Conclusions
Production of MC2 TCR T cell ATMPs is feasible. Treatment with MC2 TCR T cells, combined with epigenetic drugs and low dose IL-2, did not result in dose limiting AEs and is well tolerated. The recommended dose for phase II is expected to be at least 1x1010 TCR T cells, which is scheduled as an international, multicenter study with centralized production of T cell ATMPs.
Clinical trial identification
NCT04729543.
Editorial acknowledgement
Legal entity responsible for the study
Erasmus MC.
Funding
Dutch Cancer Society (EMCR 2015-7741).
Disclosure
A.A.M. Van der Veldt: Financial Interests, Institutional, Other, Consulting: BMS, MSD, Merck, Sanofi, Pierre Fabre, Roche, Novartis, Pfizer, Eisai, Ipsen. R. Debets: Financial Interests, Institutional, Funding, research support: MSD, Bayer; Financial Interests, Personal, Funding: Bluebird Bio, Genticel; Financial Interests, Institutional, Other: Pan Cancer T. All other authors have declared no conflicts of interest.
Resources from the same session
1112P - Immunotherapy after progression to double immunotherapy: Pembrolizumab and Lenvatinib versus conventional chemotherapy for patients with metastatic melanoma after failure of PD-1/CTLA-4 inhibition
Presenter: Dimitrios Ziogas
Session: Poster session 04
1113P - A machine learning model based on computed tomography radiomics to predict prognosis in subjects with stage IV melanoma
Presenter: Maria Teresa Maccallini
Session: Poster session 04
1114P - Deciphering unresectable in-transit metastasis in melanoma: Multi-modal and longitudinal insights
Presenter: Giuseppe Tarantino
Session: Poster session 04
1115P - Multiomics clustering of patients with cutaneous melanoma to reveal survival trends based on tumor immune evasion features
Presenter: Adeliya Leleytner
Session: Poster session 04
1116P - Application of the Scottish inflammatory prognostic score to the south-east Scotland cancer network real-world melanoma cohort
Presenter: Karim El-Shakankery
Session: Poster session 04
1117P - Intratumoral microbiota is associated with prognosis in Chinese patients with skin melanoma
Presenter: Hang Jiang
Session: Poster session 04
1118P - Immunological alterations during neoadjuvant BRAF/MEK inhibition in patients with prior unresectable regionally advanced melanoma: Translational analysis from the REDUCTOR trial
Presenter: Femke Burgers
Session: Poster session 04
1119P - Genomic and transcriptomic predictors of resistance to anti-PD1 monotherapy in patients with advanced melanoma
Presenter: Wenya Wang
Session: Poster session 04
1120P - Tumoral and peripheral immunophenotype of patients with stage II/III melanoma undergoing adjuvant immunotherapy following tumor resection
Presenter: Maria Ascierto
Session: Poster session 04
1121P - Artificial Intelligence to predict BRAF mutational status from whole slide images in melanoma
Presenter: Céline Bossard
Session: Poster session 04