SHANGHAI – Hutchison Medipharma Ltd., a Shanghai-based drug R&D subsidiary of Hutchison China Meditech, with its partner Astrazeneca plc, enrolled 90 patients at 22 sites in a global phase II trial for savolitinib (AZD6094) in papillary renal cell carcinoma (PRCC), a type of cancer that afflicts 48,000 people annually, or about 14 percent of new cases of kidney cancer in the world.

The trial is the largest of its kind for the disease, and interim results are slated for release at the American Society of Clinical Oncology (ASCO) meeting in June 2016.

Savolitinib, originally named volitinib before its registration with the World Health Organization, is a selective mesenchymal epithelial transition factor, or c-Met, inhibitor with the potential to be first in class for PRCC, which currently has no approved targeted therapies. The disease also lacks standard first-line treatments specifically for metastatic PRCC.

The phase II trial, conducted in the U.S., Canada and Europe, will test the safety and efficacy of savolitinib as a monotherapy in a 600-mg daily dose. It will be an open-label, single-arm, multicenter study designed to evaluate efficacy and safety in patients with locally advanced or metastatic PRCC.

Hutchison is keen to deepen its understanding of the relationship between c-Met aberration and clinical outcome, and said it will conduct a molecular analysis on patient tumor samples.

In a phase I study conducted in Australia, a correlation was found between positive patient outcomes for those on savolitinib and their c-Met gene status. Eight PRCC patients were treated with savolitinib. Three patients achieved a partial response; another three patients achieved stable response, while one patient who has taken the drug for more than two years has had 85 percent tumor size reduction.

In the phase II, the primary objective is to assess antitumor activity. The secondary objectives include progression-free survival, duration of response, safety and tolerability, and pharmacokinetics and pharmacodynamics.

PARTNERING WITH PHARMA

When Hutchison partnered with Astrazeneca in 2011, the news made a significant impact. With the deal, Hutchison cemented its standing as a pioneer in the field of Chinese drug discovery, being the first Chinese biotech to license out a locally discovered asset to a global pharma.

Hutchison received a $20 million up-front payment, with the potential to make $120 million in clinical and sales milestones. The deal was inked to accelerate the program as well as to help financially support Hutchison’s other unpartnered pipeline assets through the clinic. In June 2013, Hutchison received $5 million in a clinical milestone payment

“Our collaboration will support the development and commercialization of this novel oncology innovation, discovered in China, to the global market on an accelerated basis, something we could not have done alone,” said Christian Hogg, CEO of Hutchison, upon the announcement of the deal.

Hutchison has also engaged in a collaboration with Eli Lilly and Co. on fruquintinib, targeting VEGF 1/2/3. Fruquintinib is being studied in China in a phase III trial for colorectal cancer, a phase II study in non-small-cell lung cancer (NSCLC) and a phase Ib trial in gastric cancer.

That many-shot approach is being taken for savolitinib as well; there are seven phase Ib trials ongoing in China in NSCLC and gastric cancer, many in combination with other drugs.

“C-met is aberrant in many solid tumor types and we are conducting development in many of these indications,” Hogg told BioWorld Today. “Savolitinib has shown efficacy in c-Met aberrant patients in PRCC, lung, gastric and colorectal cancer.

“Savolitinib published encouraging data at ASCO 2015 in combination with AZD9291 in EGFRm tyrosine kinase inhibitor resistant non-small-cell lung cancer. Further, phase Ib studies combining savolitinib with chemotherapy [docetaxel] and targeted therapy [gefitinib] are under way and combinations with immunotherapies are planned,” Hogg added.

However, in the last 12 months, Hutchison has had to drop two of its partnered projects, demonstrating both the risks of novel drug development, but also the value of a diversified pipeline.

In August, an agreement with Johnson & Johnson unit Janssen for a preclinical inflammation candidate, HMPL-507, was terminated, as was a phase III study, partnered with Nestle, testing the botanical HMPL-004 in ulcerative colitis.