Clovis Oncology, Inc. and Array BioPharma have announced an agreement for the discovery of a novel KIT inhibitor targeting resistance mutations for the treatment of GIST.
GIST is a gastrointestinal cancer diagnosed each year in more than 12,000 patients in the US and EU and 2,500 in Japan.
Currently approved therapies for GIST include the tyrosine kinase inhibitors (TKIs) Gleevec® (imatinib), and Sutent® (sunitinib), typically used first- and second-line respectively.
Each inhibits some KIT mutations, but acquired resistance due to secondary KIT mutations occurs in the majority of GIST patients, resulting in disease progression.
Patients who present with metastatic GIST have a five-year survival rate of approximately 50 percent.
Exon 17 resistance mutations are considered the most difficult to treat, and typically emerge after other TKI therapy in at least 50 percent of patients with progressive disease.
None of the currently-approved therapies inhibit exon 17 mutations, nor do the current development-stage drugs targeting GIST.
The goal of this collaboration is to discover a potent, oral inhibitor of KIT mutations, including all exon 17 resistance mutations.
“Virtually all GIST patients on first-line therapy progress due to the persistent and resistant nature of the disease,” said Dr. Jonathan Fletcher, Associate Professor, Harvard Medical School.
Dr. Fletcher continued, “Therefore, there is significant unmet medical need for patients with advanced GIST. Specifically, we see a need for therapy active against the KIT exon 17 mutations.”
“Array has a proven track record of success in the discovery of novel drugs and we are very pleased to collaborate with them to identify our fourth product candidate,” said Patrick J. Mahaffy, president and CEO of Clovis Oncology.
Mahaffy continued, “This program is highly complementary to our current programs, takes advantage of our experience in developing targeted therapies with companion diagnostics and represents another cost effective approach to building our pipeline. If successful, we would hope to file an IND within three years, which is also well-timed as our existing pipeline matures.”
“We are delighted to collaborate with Clovis on this challenging cancer target,” said Ron Squarer, Chief Executive Officer, Array BioPharma.
Squarer continued, “With 10 Array-invented drugs currently in Phase 2 clinical development and vast experience in the structure-based discovery of kinase inhibitors, we are confident we will create value for Clovis and ourselves with the ultimate goal of improving treatment for cancer patients.”
Under the terms of the agreement, Clovis Oncology and Array BioPharma will collaborate on the discovery of the compound.
Clovis will be fully responsible for all aspects of the pre-clinical and clinical development and commercialization, including development of a companion diagnostic to prospectively identify patients with specific KIT mutations. Financial terms were not disclosed.