beta-lapachone (ARQ 761) / Merck (MSD) - LARVOL DELTA

ARQ-761 Treatment With Gemcitabine/Nab-Paclitaxel Chemotherapy In Pancreatic Cancer (clinicaltrials.gov) - P1 | N=17 | Terminated | Sponsor: University of Texas Southwestern Medical Center | Suspended ➔ Terminated; The study placed on temporarily hold to enrollment due to quality testing necessary for the study drug.

Trial termination • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

β-Lapachone Selectively Kills Hepatocellular Carcinoma Cells by Targeting NQO1 to Induce Extensive DNA Damage and PARP1 Hyperactivation. (PubMed, Front Oncol) - "β-Lapachone (ARQ761 in clinical form) selectively kill NADPH: quinone oxidoreductase 1 (NQO1)-overexpressing cancer cells...Our data suggest that NQO1 is an ideal potential biomarker, and relatively high NQO1:CAT ratios in HCC tumors but low ratios in normal tissues offer an optimal therapeutic window to use β-Lapachone. This study provides novel preclinical evidence for β-Lapachone as a new promising chemotherapeutic agent for use in NQO1-positive HCC patients."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CAT • NQO1

ARQ-761 Treatment With Gemcitabine/Nab-Paclitaxel Chemotherapy In Pancreatic Cancer (clinicaltrials.gov) - P1; N=20; Suspended; Sponsor: University of Texas Southwestern Medical Center; Trial completion date: Jul 2021 ➔ Jul 2022

Clinical • Trial completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A phase I/Ib, multi-center trial of ARQ-761 (Beta-Lapachone) with gemcitabine/nab-paclitaxel in patients with advanced pancreatic cancer (ESMO 2019) - P1; "We report results of a phase 1b clinical trial of the novel NQO1 bioactivatable compound, ARQ761, in combination with gemcitabine/nab-paclitaxel. Treatment related toxicities were observed which were noted in preclinical models and managed with routine dose adjustment. Clinical trial identification: NCT02514031."

Clinical • P1 data • PARP Biomarker

NQO1-dependent, tumor-selective radiosensitization of non-small cell lung cancers. (PubMed, Clin Cancer Res) - "Our data suggest that combination of sublethal doses of ß-lap and IR is a viable approach to selectively treat NQO1-overexpressing NSCLC and warrant a clinical trial using low-dose IR + ß-lapachone against patients with NQO1+ NSCLCs."

Journal • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer

Clinical Trial of ARQ 761 in Advanced Solid Tumors (clinicaltrials.gov) - P1; N=91; Completed; Sponsor: University of Texas Southwestern Medical Center; Active, not recruiting ➔ Completed; N=27 ➔ 91

Clinical • Enrollment change • Trial completion

Mesoporous Silica Nanoparticle-Based Combination of NQO1 Inhibitor and 5-Fluorouracil for Potent Antitumor Effect Against Head and Neck Squamous Cell Carcinoma (HNSCC). (PubMed, Nanoscale Res Lett) - "The main aims were to study the inhibitory effect of ß-lapachone (ARQ761 in clinical form) in HNSCC and to study the combinational effect of 5-FU and ß-lap in improving the therapeutic efficacy in HNSCC. Notable decrease in tumor volume was observed with the physical mixture of 5-FU+ß-lap; however, combined treatment of carrier-based 5-FU and ß-lap (FNQ-MSN) significantly delayed the tumor growth and prolonged the survival of tumor-bearing xenograft mice. These findings suggest the potential of NQO1 inhibitor in enhancing the chemotherapeutic potential of 5-FU in the treatment of HNSCC."

Journal • NQO1

ARQ-761 Treatment With Gemcitabine/Nab-Paclitaxel Chemotherapy In Pancreatic Cancer (clinicaltrials.gov) - P1; N=20; Suspended; Sponsor: University of Texas Southwestern Medical Center; Recruiting ➔ Suspended

Clinical • Trial suspension

ARQ761 + PARP Inhibitor in Refractory Solid Tumors (clinicaltrials.gov) - P1; N=0; Withdrawn; Sponsor: University of Texas Southwestern Medical Center; N=40 ➔ 0; Trial completion date: Aug 2023 ➔ May 2019; Not yet recruiting ➔ Withdrawn; Trial primary completion date: Aug 2022 ➔ May 2019

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal

Phase 1 study of ARQ 761, a β-lapachone analogue that promotes NQO1-mediated programmed cancer cell necrosis. (PubMed, Br J Cancer) - "ARQ 761 has modest single-agent activity, which appears associated with tumour NQO1 expression. Principal toxicities include anaemia and possible methemoglobinaemia."

Journal • P1 data

Clinical Trial of ARQ 761 in Advanced Solid Tumors (clinicaltrials.gov) - P1; N=27; Active, not recruiting; Sponsor: University of Texas Southwestern Medical Center; Trial completion date: Jan 2019 ➔ Jan 2020; Trial primary completion date: Jan 2019 ➔ Feb 2017

Clinical • Trial completion date • Trial primary completion date

ARQ761 + PARP Inhibitor in Refractory Solid Tumors (clinicaltrials.gov) - P1; N=40; Not yet recruiting; Sponsor: University of Texas Southwestern Medical Center; Initiation date: Jan 2019 ➔ Jun 2019

Combination therapy • Trial initiation date