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Clinical Trials

Date: 2012-06-04

Type of information: Results

phase: 3

Announcement: results

Company: Bayer Healthcare (Germany)

Product: regorafenib (BAY 73-4506)

Action mechanism:

multi-kinase inhibitor. Stivarga® (regorafenib) is an oral multi-kinase inhibitor that inhibits various kinases within the mechanisms involved in tumor growth and progression - angiogenesis, oncogenesis and the tumor microenvironment. In preclinical studies, Stivarga inhibits several angiogenic VEGF receptor tyrosine kinases that play a role in tumor neoangiogenesis (the growth of new blood vessels). In addition to VEGFR 1-3 it also inhibits various oncogenic and tumor microenvironment kinases including TIE-2, RAF-1, BRAF, BRAFV600, KIT, RET, PDGFR, and FGFR, which individually and collectively impact upon tumor growth, formation of a stromal microenvironment and disease progression.

Disease:

metastatic and/or unresectable gastrointestinal stromal tumors (GIST) which has progressed after at least imatinib and sunitinib as prior treatments

Therapeutic area: Cancer - Oncology

Country:

Trial details:

GRID (GIST - Regorafenib In Progressive Disease) was a randomized, double-blind, placebo-controlled, multi-center, cross-over Phase III study of regorafenib for the treatment of GIST. It enrolled 199 patients whose disease has progressed despite prior treatment with imatinib and sunitinib. Patients were randomized in a 2:1 ratio to receive either regorafenib (160 mg once daily, 3 weeks on/1 week off) plus best supportive care (BSC) or placebo plus BSC to evaluate efficacy and safety. Subjects receiving placebo who experienced disease progression were offered regorafenib treatment. The primary endpoint of this trial is progression-free survival, and secondary endpoints include overall survival, time to progression, disease control rate, tumor response rate, and duration of response.

The GRID study was sponsored by Bayer with academic leadership from the principal investigator George Demetri, M.D., Director of the Ludwig Center at the Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, U.S.A. The study started in January 2011 and completed enrollment by July 2011.

Latest news:

* On June 4, 2012, Bayer HealthCare has announced data from the Phase III GRID (GIST – Regorafenib In Progressive Disease) trial evaluating regorafenib in patients with metastatic and/or unresectable gastrointestinal stromal tumors (GIST) whose disease had progressed despite prior treatment with imatinib and sunitinib. The GRID study met its primary endpoint of improvement in progression-free survival (PFS) (HR=0.27, p<0.0001). The median PFS was 4.8 months in the regorafenib arm versus 0.9 months in the placebo arm. These data have been presented as a late-breaking abstract in an oral abstract session at the 48th Annual Meeting of the ASCO in Chicago (LBA No. 10008). The most common drug-related, treatment-emergent adverse events (occurring in at least 10% of patients during double-blind treatment) included hand-foot skin reaction (56.1% vs.15.2%), hypertension (48.5% vs. 16.7%), diarrhea (40.9% vs.7.6%), fatigue (38.6% vs. 27.3%), oral mucositis (37.9% vs. 9.1%), alopecia (23.5% vs. 3.0%), hoarseness (22.0% vs. 4.5%), anorexia (20.5% vs. 7.6%), rash, maculopapular (18.2% vs. 3.0%), nausea (15.9% vs. 9.1%), constipation (15.2% vs. 7.6%), myalgia (13.6% vs. 9.1%), and voice alteration (11.4% vs. 3.0%) for patients receiving regorafenib as compared to placebo.
Bayer has already submitted a New Drug Application to the FDA for regorafenib for the treatment of patients with metastatic colorectal cancer (mCRC). The company also plans to submit a New Drug Application for regorafenib in GIST in the second half of 2012.

* On April 3, 2012, Bayer HealthCare has announced positive results from its Phase III trial GRID (GIST - Regorafenib In Progressive Disease) evaluating regorafenib (BAY 73-4506) for the treatment of patients with metastatic and/or unresectable gastrointestinal stromal tumors (GIST) whose disease has progressed despite prior treatment with imatinib and sunitinib. The trial met its primary endpoint of statistically significantly improving progression-free survival. In this trial, the safety and tolerability of regorafenib were generally as expected. Detailed data from the study are expected to be presented at an upcoming scientific meeting. Bayer plans to submit regorafenib for marketing authorization in the treatment of metastatic and/or unresectable GIST based on these data.

* On January 10, 2011, Bayer Healthcare has announced the initiation of patient enrollment in the Phase III Study GRID.

Is general: Yes