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.
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Acknowledgements
The authors wish to acknowledge Christelle Descot of Clinical Development Department, Ipsen and Frederique Baton of the Medical Affairs Department, Ipsen, for the contributions to the clinical development program.
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Funding
This work was supported by Ipsen. Medical writing support provided by Christine McKillop PhD, MedSciMedia Ltd. and funded by Ipsen.
Conflicts of Interest
Bernard Escudier has received consulting fees and honoraria from Novartis, Pfizer, BMS, Exelixis, Bayer, and Roche. Sandrine Faivre has received consulting fees and honoraria from Bayer, Novartis, Merck Serono, Lilly, Ipsen, and Celgene, and support for travel to meetings from Ipsen. Eric Van Cutsem has received grant funding from Ipsen. Nathalie Germann is an employee of Ipsen Innovation and holds stock/share options from Ipsen. Jean-Christophe Pouget is an employee of Ipsen Innovation. Ruth Plummer has received support for travel to meetings and costs relating to recruitment to the study from Ipsen. Fiona Thistlethwaite has received support for travel to meetings and provision of writing assistance from Ipsen. Robert Jones has received grant funding, consulting fees and honoraria, funding for travel, and provision of writing assistance from Ipsen. Julien Edeline has received consulting fees and honoraria from Bayer, BTG, BMS, and Novartis. The other authors declare no conflict of interest.
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Escudier, B., Faivre, S., Van Cutsem, E. et al. A Phase II Multicentre, Open-Label, Proof-of-Concept Study of Tasquinimod in Hepatocellular, Ovarian, Renal Cell, and Gastric Cancers. Targ Oncol 12, 655–661 (2017). https://doi.org/10.1007/s11523-017-0525-2
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DOI: https://doi.org/10.1007/s11523-017-0525-2