Bernard Escudier1, Sandrine Faivre2, Eric Van Cutsem3, Nathalie Germann4, Jean-Christophe Pouget4, Ruth Plummer5, Ignace Vergote3, Fiona Thistlethwaite6, Georg A Bjarnason7, Robert Jones8, Helen Mackay7, Julien Edeline9, Laetitia Fartoux10, Hal Hirte11, Amit Oza8. 1. Oncology Department, Gustave-Roussy, 114 Rue Edouard Vaillant, 94800, Villejuif, France. escudier@gustaveroussy.fr. 2. Hôpitaux Universitaires Paris Nord Val de Seine (HUPVNS), Paris, France. 3. University Hospitals Gasthuisberg and KULeuven, Leuven, Belgium. 4. Ipsen Innovation, Les Ulis, France. 5. Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, UK. 6. The Christie NHS Foundation Trust, Manchester, UK. 7. Sunnybrook Odette Cancer Centre, Toronto, Canada. 8. Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK. 9. Centre Eugène Marquis, Rennes, France. 10. Saint-Antoine University Hospital, Paris, France. 11. Juravinski Cancer Centre, McMaster University, Hamilton, Canada.
Abstract
BACKGROUND: Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors. PATIENTS AND METHODS: This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers. Tasquinimod was given orally every day (0.5 mg/day for at least 2 weeks, with dose increase to 1 mg/day) until radiological progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria, intolerable toxicity, or patient withdrawal. The primary efficacy endpoint was progression-free survival (PFS) rate according to RECIST 1.1 by central assessment. RESULTS: Interim futility analyses at 8 weeks (6 weeks for the gastric cancer cohort) found adequate clinical activity of tasquinimod only in the hepatocellular cohort and recruitment to the other three cohorts was stopped. PFS rates were 26.9% at 16 weeks, 7.3% at 24 weeks, 13.2% at 16 weeks, and 9.5% at 12 weeks, respectively, in hepatocellular, ovarian, renal cell, and gastric cancer cohorts. The pre-defined PFS threshold was not reached in the hepatocellular cancer cohort at the second stage of the trial. The most common treatment-related adverse events were fatigue (48.5%), nausea (34.1%), decreased appetite (31.7%), and vomiting (24.6%). CONCLUSIONS: This study failed to demonstrate clinical activity of tasquinimod in heavily pre-treated patients with advanced hepatocellular, ovarian, renal cell, and gastric cancer. TRIAL REGISTRATION: NCT01743469.
BACKGROUND:Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors. PATIENTS AND METHODS: This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers. Tasquinimod was given orally every day (0.5 mg/day for at least 2 weeks, with dose increase to 1 mg/day) until radiological progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria, intolerable toxicity, or patient withdrawal. The primary efficacy endpoint was progression-free survival (PFS) rate according to RECIST 1.1 by central assessment. RESULTS: Interim futility analyses at 8 weeks (6 weeks for the gastric cancer cohort) found adequate clinical activity of tasquinimod only in the hepatocellular cohort and recruitment to the other three cohorts was stopped. PFS rates were 26.9% at 16 weeks, 7.3% at 24 weeks, 13.2% at 16 weeks, and 9.5% at 12 weeks, respectively, in hepatocellular, ovarian, renal cell, and gastric cancer cohorts. The pre-defined PFS threshold was not reached in the hepatocellular cancer cohort at the second stage of the trial. The most common treatment-related adverse events were fatigue (48.5%), nausea (34.1%), decreased appetite (31.7%), and vomiting (24.6%). CONCLUSIONS: This study failed to demonstrate clinical activity of tasquinimod in heavily pre-treated patients with advanced hepatocellular, ovarian, renal cell, and gastric cancer. TRIAL REGISTRATION: NCT01743469.
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