PHASE IA/IB STUDY OF RS-0139
A NOVEL TUMOR-TARGETED DELIVERY OF DOCETAXEL, IN PATIENTS WITH RECURRENT,
LOCALLY ADVANCED, OR METASTATIC NON-SMALL CELL LUNG CANCER
ESMO 2022, 9-13 September, Paris
Presenters
Hakan Sedat Orer
Citation
Annals of Oncology (2022) 33 (suppl_7): S448-S554. 10.1016/annonc/annonc1064
Authors
H.S. Orer1, G. Nomak2, B.O. Oksuzoglu3, R.S. Senturk4, Y. Eralp5, F.P. Yumuk6, H.S. Nomak7, R. Sanyal8
Background
Docetaxel (DTX) is an anti-microtubule agent registered for multiple indications and is usually administered 3-weekly at doses of 60-100 mg/m2. Important limitations of DTX include acute hypersensitivity reactions, neutropenia, neuropathy, fatigue and nausea. RS-0139 is developed as a DTX-releasing, tumor-targeted prodrug. DTX is covalently bound to a polymer backbone, together with a targeting peptide, which shows high affinity to avb3, avb5 and avb6 integrin receptors highly expressed on tumor cell surface. Once RS-0139 is up-taken by the cell, the covalent bond is cleaved to release DTX in the cytoplasm. RS-0139 gains the investigational new drug status since DTX is covalently modified for the targeted treatment. The physical properties of RS-0139, pharmacokinetic profile and improved aqueous solubility may provide an advantage over the currently used taxanes. In preclinical studies, enzymatically cleavable covalent conjugation of DTX enabled sustained-release inside the tumor, reducing adverse effects due to limited circulating free DTX. Hence, RS-0139 showed superior tolerability than DTX in healthy animals. Besides, the dosing frequency decreased owing to the increased half-life. Preclinical data strongly support the clinical translation of this novel nanomedicine for the treatment of solid tumors.
Trial design
This is a phase Ia/Ib open-label, multicenter, dose-escalation and expansion study to evaluate the safety and tolerability of RS-0139 monotherapy in NSCLC. Patients who progressed after standard therapy are eligible for the study. In Phase Ia, patients receive RS-0139 (IV) at escalating doses (75-200 mg/m2). The protocol consists of an accelerated titration design until the recommended dose for Phase Ib is elicited and switched to standard 3+3 design in case of grade 2 toxicity. Phase Ib will be initiated following the determination of the recommended dose for RS-0139 upon evaluation of all available safety and PK data and 6 patients will receive 3 cycles in every 21 days. The primary endpoint is the determination of the MTD of RS-0139. The study is open for enrollment in 2 sites. Two of the planned 16 patients have been enrolled to date.
