Abstract 2555
Background
TP-0903 is a novel, oral small molecule AXL kinase inhibitor impacting oncogenesis and resistance. AXL is upregulated in many solid tumors and influences the mesenchymal phenotype, which drives resistance to targeted cancer therapeutics, traditional chemotherapies, and immuno-oncology agents.
Methods
A dose escalation study was performed to examine the safety and clinical activity of TP-0903 in patients with advanced solid tumors. Patients received oral TP-0903 once daily for 21 of 28-day cycles. Nine dose levels were explored using modified 3 + 3 dose escalation rules. The primary objective of the trial was to identify the maximum tolerated dose of TP-0903 prior to expanding into refractory colorectal, platinum refractory/resistant ovarian cancer and TP-0903 in combination with immunotherapy or EGFR tyrosine kinase inhibitor in immunotherapy-resistant tumors or non-small cell lung cancers. Potential biomarkers were evaluated using liquid biopsies and pre-and post-dose tumor biopsies will be reported.
Results
Thirty-six patients were enrolled between December 2016 and April 2019 receiving 1.5 to 37mg/m2 over 9 cohorts. The most frequently observed >Gr3 AEs were thrombocytopenia (3), anemia (2), nausea (2), syncope (2), and vomiting (2), all manageable with supportive care. Grade 4 thrombocytopenia was the dose limiting toxicity observed in one patient in cohort 8 (28 mg/m2), reoccurring as grade 3 thrombocytopenia in 2 patients in cohort 9 (37mg/m2) without meeting DLT criteria. Patients are currently still ongoing in cohort 9. Eleven patients, (11/36, 30.6%), had stable disease with a median duration of 3.7 months (range 1.6 to 7.4+ months). Baseline serum soluble AXL of all enrolled patients was determined by immunoassay and indicated higher levels in patients with documented stable disease vs. progressive disease (p = 0.0332).
Conclusions
The oral small molecule AXL kinase inhibitor TP-0903 is well tolerated with a manageable safety profile. Hematologic toxicity was observed as a DLT. Future studies will evaluate the role of TP0903 in selected disease cohorts as monotherapy and in combination. Serum soluble AXL will be evaluated as a potential predictive biomarker of response.
Clinical trial identification
NCT: 02729298.
Editorial acknowledgement
Legal entity responsible for the study
Tolero Pharmaceuticals, Inc.
Funding
Tolero Pharmaceuticals, Inc.
Disclosure
J. Sarantopoulos: Research grant / Funding (institution): Tolero. G. Fotopoulos: Research grant / Funding (institution): Tolero Pharmaceuticals. F.Y. Tsai: Advisory / Consultancy: Tempus Lab; Officer / Board of Directors, Co-Founder: Caremission LLC; Shareholder / Stockholder / Stock options: Salarius Pharmaceuticals. M.S. Beg: Research grant / Funding (institution): Tolero Pharmaceuticals. A.A. Adjei: Research grant / Funding (institution): Tolero Pharmaceuticals. Y. Lou: Research grant / Funding (institution): Tolero Pharmaceuticals; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Stem Centrx; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Vaccinex; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): MacroGenics. M. Seetharam: Research grant / Funding (institution): Tolero Pharmaceuticals. M.A. Villalona-Calero: Research grant / Funding (institution): Tolero Pharmaceuticals; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Bristol Meyers; Research grant / Funding (institution): Novocure; Research grant / Funding (institution): Guardant. J. Melear: Research grant / Funding (institution): Tolero Pharmaceuticals. M. Janat-Amsbury: Full / Part-time employment: Tolero Pharmaceuticals. H. Beever: Full / Part-time employment: Tolero Pharmaceuticals. L. Mouritsen: Full / Part-time employment: Tolero Pharmaceuticals. M. Wade: Full / Part-time employment: Tolero Pharmaceuticals. B.V. Bryan: Full / Part-time employment: Tolero Pharmaceuticals. D.J. Bearss: Leadership role, Full / Part-time employment: Tolero Pharmaceuticals.
Resources from the same session
6171 - Molecular EGFR/PD-L1 profile of glioblastoma: Hints for therapeutic strategies
Presenter: Wojciech Szopa
Session: Poster Display session 1
Resources:
Abstract
4418 - Role of Intraoperative MRI (iMRI) in neurosurgery, potential imaging tool for maximizing gross total resection (GTR) rate of CNS tumours.
Presenter: Shweta Wadhwa
Session: Poster Display session 1
Resources:
Abstract
4791 - Tumor related impairments of neurocognitive functions in patients with brain metastases
Presenter: Lei Wen
Session: Poster Display session 1
Resources:
Abstract
5372 - Is radiation therapy influencing Alzheimer’s in Brain and Head and Neck Cancers?
Presenter: Anas Saad
Session: Poster Display session 1
Resources:
Abstract
2329 - Mature Treatment Results of 120 Cases of Acoustic Neuroma Treated with Cyberknife at a single institution.
Presenter: Shawn Malone
Session: Poster Display session 1
Resources:
Abstract
3207 - A phase II/III trial of high-dose, intermittent sunitinib in patients with recurrent glioblastoma: the STELLAR study
Presenter: Cyrillo Brahm
Session: Poster Display session 1
Resources:
Abstract
3589 - CNS penetration and Preliminary Efficacy of Sacutizumab Govitecan in Breast Brain Metastasis and Glioblastoma: A Surgical Study
Presenter: Andrew Brenner
Session: Poster Display session 1
Resources:
Abstract
1969 - Wedge resection with omission of lymph node dissection as an optional treatment strategy in octogenarians or older with early stage non-small cell lung cancers
Presenter: Takahiro Mimae
Session: Poster Display session 1
Resources:
Abstract
5116 - Characterization of lung tumorspheres reveals cancer stem-like cells potential targets and prognostic markers in non-small cell lung cancer
Presenter: Alejandro Herreros Pomares
Session: Poster Display session 1
Resources:
Abstract
5823 - Pulmonary tumor-draining vein exosomal lincRNA-p21 levels impacts non-small cell lung cancer prognosis
Presenter: Joan Castellano
Session: Poster Display session 1
Resources:
Abstract