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Treatment of metastatic and/or unresectable GIST: Bayer has submitted a “New Drug Application (NDA)” to the FDA for Regorafenib.

End of August 2012, Bayer HealthCare has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for its oral multi-kinase inhibitor Regorafenib for the treatment of metastatic and/or unresectable GIST (Gastrointestinal Stromal Tumours) in patients whose disease has progressed despite prior treatment with other kinase inhibitors. Usually these prior therapy options are Imatinib (Glivec®) as a first-line-treatment and Sunitinib (Sutent®) as a second-line-treatment.

The submission is supported by data from the Phase III GRID (GIST – Regorafenib In Progressive Disease) trial. The study evaluated Regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients with metastatic and/or unresectable GIST whose disease had progressed despite prior treatment with Imatinib and Sunitinib. Regorafenib plus BSC significantly improved progression-free survival compared to placebo plus BSC. The overall safety and tolerability profile for Regorafenib in the GRID study was consistent with results from previous studies.

The GRID trial was a randomized, double-blind, placebo-controlled, multi-centre, Phase III study of Regorafenib for the treatment of GIST. It randomized 199 patients whose disease had progressed despite prior treatment with Imatinib and Sunitinib. Patients were randomized in a 2:1 ratio to receive either Regorafenib plus BSC or placebo plus BSC to evaluate efficacy and safety. Each treatment cycle consisted of 160 mg Regorafenib (or matching placebo) once daily for three weeks on / one week off plus BSC. The primary endpoint was progression-free survival, and secondary endpoints included overall survival, time to progression, disease control rate, tumour response rate, and duration of response. The safety and tolerability of the two treatment groups were also compared. Results from this study were presented at the ASCO-Meeting in June 2012.

Regorafenib is an investigational, oral, multi-kinase inhibitor targeting three key mechanisms of tumour growth and progression – angiogenesis, oncogenesis, and the tumor microenvironment. In preclinical studies, Regorafenib inhibits several angiogenic VEGF receptor tyrosine kinases that play a role in tumour neo-angiogenesis and lymph-angiogenesis (the growth of new blood vessels and lymphatic vessels).

It also inhibits various oncogenic and tumour microenvironment kinases including KIT, RET, PDGFR, and FGFR, which individually and collectively impact upon tumour growth, formation of a stromal microenvironment and disease progression. Regorafenib is currently being investigated in clinical trials for its potential to treat patients with various tumour types. Regorafenib is an investigational agent and is not approved by the European Medicines Agency (EMA) or other health authorities.

Earlier this year, Bayer submitted a Marketing Authorization Application to the European Medicines Agency (EMA) and a New Drug Application to the FDA for Regorafenib for the treatment of patients with metastatic colorectal cancer (mCRC). The FDA has granted priority review status to the application for Regorafenib in mCRC.

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