A multicenter phase 1/2 study investigating the safety, pharmacokinetics, pharmacodynamics and efficacy of a small molecule antimetabolite, RX-3117, plus nab-paclitaxel in pancreatic adenocarcinoma.

Autor:	Babiker, Hani, Schlegel, Peter J., Hicks, Lee G., Bullock, Andrea J., Burhani, Nafisa, Mahadevan, Daruka, Elquza, Emad, Borad, Mitesh J., Benaim, Ely, Peterson, Christine, Heaton, Callie, Ocean, Allyson J.
Předmět:	PANCREATIC tumors ADENOCARCINOMA SAFETY DRUG efficacy RESEARCH CLINICAL trials DRUG tolerance INTRAVENOUS therapy DIARRHEA NAUSEA METASTASIS ANTINEOPLASTIC agents MEDICAL cooperation TREATMENT duration ANTIMETABOLITES TREATMENT effectiveness COMPARATIVE studies KAPLAN-Meier estimator SURVIVAL analysis (Biometry) DESCRIPTIVE statistics PACLITAXEL ETHNIC groups DRUG side effects FATIGUE (Physiology) DATA analysis software PHARMACODYNAMICS
Zdroj:	Investigational New Drugs; Feb2022, Vol. 40 Issue 1, p81-90, 10p
Abstrakt:	Summary: Background RX-3117 is an oral small molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by cancer cells over-expressing uridine cytidine kinase 2 (UCK2). Single agent RX-3117 demonstrated efficacy in a phase I trial in patients with metastatic (met) pancreatic adenocarcinoma (PC). RX-3117 plus nab-paclitaxel (nab-Pac) was evaluated as a first line treatment in met-PC cancer. Methods This was a multicenter open label phase I/II 2-stage study investigating the combination of RX3117 plus nab-Pac in the frontline treatment of patients with met-PC. The phase I portion comprised a dose de-escalation design with primary objectives of determining the safety, tolerability and recommended phase 2 dose (RP2D) of RX-3117 (orally 700, 600, or 500 mg/day for 5 consecutive days with 2 days off/week) plus nab-Pac (intravenous (IV) 125 mg/m2 once weekly) for 3 weeks with 1 week off per a 4-week cycle. The primary objective was to determine the antitumor efficacy. Results 46 patients were enrolled (22 male/24 female; median age 67; 91% Caucasian). The RP2D of RX-3117 plus nab-Pac was 700 mg/day. No dose-limiting toxicities were observed (DLTs). The overall response rate (ORR) was 23.1% and disease control rate (DCR) 74.4%. RX-3117 pharmacokinetics (PK) results were similar to previously reported monotherapy phase 1 trial. All patients experienced a treatment emergent adverse event (TEAE) with the most common diarrhea, nausea, and fatigue.10.9% of patients experienced a serious adverse event (SAE) related to the combination. Conclusion RX-3117 plus nab-Pac in newly diagnosed met-PC patients demonstrated tolerability, safety, and early treatment efficacy. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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