Abstract 3630
Background
The overexpression of hypoxia induced factor 1a/2a in ccRCC leads to up-regulation of vascular endothelial growth factor (VEGF) that results in increased angiogenesis, tumor metastasis, and treatment resistance. Using several preclinical xenograft models, it has been demonstrated that therapeutic doses and schedules of the selenium-containing molecules, seleno-L-methionine (SLM) and methylselenocysteine caused enhanced degradation of HIF1α/2α, down-regulation of oncogenic miRNA-210 and 155, up-regulation tumor suppressor miRNA-664 and LET-7b, and stabilization of tumor vasculature, yielding higher tumor drug uptake and protection from toxic side effects when combined with chemotherapeutic and VEGF-targeted agents.
Methods
This is a phase I (3 + 3 design) dose finding trial of SLM (2500, 3000 or 4000 µg) given orally twice daily for 14 days, followed by once a day in combination with standard dose axitinib to patients with metastatic ccRCC. Primary endpoint is safety; secondary endpoint is efficacy including overall response rate, progression free survival and overall survival.
Results
Twelve evaluable patients (pts) with metastatic ccRCC who progressed on one or more prior lines of treatment were enrolled. The first 3 pts were treated at 4000 µg, the second and third 3 pts were treated at 2500 and 3000 µg respectively. Additional 3 pts were added to 4000 µg. No dose limiting toxicity was seen. Most common AEs included fatigue, diarrhea, hypertension, nausea, anorexia, cough, proteinuria and weight loss. Of the 4000 µg cohort, 2 pts achieved complete response with ongoing responses at 31 and 29 months, 1 pt had partial response (PR) for 24 months. Of the 2500 µg cohort, 1 pt with ongoing PR for 21 months. The 3000 µg cohort, one pt has ongoing PR for 12 months.
Conclusions
SLM of 4000 µg is safe and the recommended phase 2 dose in combination with standard dose axitinib. The combination has promising efficacy with phase 2 trial is ongoing. Further data to be presented at the meeting.
Clinical trial identification
NCT02535533.
Editorial acknowledgement
NA
Legal entity responsible for the study
Yousef Zakharia.
Funding
Holden Comprehensive Cancer Centre.
Disclosure
Y. Zakharia: Advisory / Consultancy: Amgen; Advisory / Consultancy: Roche Diagnostics; Advisory / Consultancy: Novartis; Advisory / Consultancy: Jansen; Advisory / Consultancy: Eisai; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Castle Bioscience; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Bayer; Advisory / Consultancy: Array. M. Milhem: Advisory / Consultancy: Amgen; Advisory / Consultancy: Trieza; Advisory / Consultancy: Biontech; Advisory / Consultancy: Blueprint Medicines Corporation; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Array. All other authors have declared no conflicts of interest.
Resources from the same session
2963 - Analytical performance of the Resolution-HRD plasma assay used to identify mCRPC patients with biallelic disruption of DNA repair genes for treatment with niraparib
Presenter: Ira Pekker
Session: Poster Display session 3
Resources:
Abstract
3523 - Results of a global external quality assessment scheme for EGFR testing on liquid biopsy
Presenter: Nicola Normanno
Session: Poster Display session 3
Resources:
Abstract
3295 - Clinical impact of plasma Next-Generation Sequencing (NGS) in advanced Non-small cell lung cancer (aNSCLC)
Presenter: Laura Bonanno
Session: Poster Display session 3
Resources:
Abstract
5632 - Feasibility study of a ctEGFR prototype assay on the fully automated Idylla™ platform
Presenter: Martin Reijans
Session: Poster Display session 3
Resources:
Abstract
3614 - Enhanced Access to EGFR Molecular Testing in NSCLC using a Cell-Free DNA Tube for Liquid Biopsy
Presenter: Theresa May
Session: Poster Display session 3
Resources:
Abstract
5664 - Analysis of circulating tumor DNA in paired plasma and sputum samples of EGFR-mutated NSCLC patients
Presenter: Christina Grech
Session: Poster Display session 3
Resources:
Abstract
4945 - Liquid biopsy and Array Comparative Genomic Hybridization (aCGH)
Presenter: Panagiotis Apostolou
Session: Poster Display session 3
Resources:
Abstract
5746 - Next-generation sequencing panel verification to detect low frequency single nucleotide and copy number variants from mixing cell line studies
Presenter: Rocio Rosas-Alonso
Session: Poster Display session 3
Resources:
Abstract
5901 - Automated rarefaction analysis for precision B and T cell receptor repertoire profiling from peripheral blood and FFPE-preserved tumor
Presenter: Luca Quagliata
Session: Poster Display session 3
Resources:
Abstract
2027 - A Heptamethine cyanine dye is a potential diagnostic marker for Myeloid-Derived Suppressor Cells
Presenter: Chaeyong Jung
Session: Poster Display session 3
Resources:
Abstract