LONDON—The Cancer Research UK Drug Development Office (DDO)has completed an agreement with Clovis Oncology Inc., of Boulder, Colo., forthe licensing of data from the Cancer Research UK Phase II clinical trial ofrucaparib (AG014699) in breast and ovarian cancer patients with known mutationsin their BRCA 1 or 2 genes.
As part of the agreement, Clovis will gain access to theclinical data from this study, and Cancer Research UK will receive licensefees.
Research initially conducted in Cancer Research UK-fundedlaboratories at the Northern Institute for Cancer Research, and subsequently incollaboration with Agouron Pharmaceuticals—which later became part of PfizerGRD—led to the development of the poly(ADP-ribose) polymerase inhibitorrucaparib. Rucaparib is a PARP inhibitor being investigated as a potentialanticancer agent. It is thought to inhibit the contraction of isolated vascularsmooth muscle, including that from the tumors of cancer patients.
According to the literature, it also reduces the migrationof some cancer and normal cells in culture. It can be administered orally intablet form. It had undergone Phase I clinical trials for patients withadvanced solid tumors prior to initiation of Phase II clinical trials formetastatic breast and ovarian cancer with known BRCA 1 or BRCA 2 mutation. Asof November 2012, four clinical trials of rucaparib were recruiting patients.
The DDO points out that the average woman in the UnitedKingdom has a 12.5-percent chance of developing breast cancer at some point inher life. But a female BRCA 1 carrier, such as Angelina Jolie, who recently—andbravely—went public with her decision to have a double mastectomy, has betweena 60- and 90-percent chance of developing breast cancer. In other words,between 60 and 90 out of every 100 BRCA 1 carriers go on to develop breastcancer. They also have around a 40-to 60-percent chance of developing ovariancancer.
"This exciting deal underlines the value of the data fromthis Cancer Research UK trial," says Dr. Nigel Blackburn, director of drugdevelopment at the DDO. "We will look forward to the ongoing clinicaldevelopment of this very promising agent by Clovis Oncology with greatinterest."
The Cancer Research UK DDO has a number of collaborations ofthis type with both large pharmaceutical and smaller biotechnology companies,he notes. This particular collaborative trial came about when Pfizer Inc. wasdeveloping the compound, which was subsequently licensed and transferred toClovis Oncology.
A DDO spokesman points out that rucaparib differs from otherdrugs, and that there are no currently marketed therapies specifically forpatients with mutations of BRCA 1 or 2.
"Rucaparib is a highly potent and selective PARP inhibitor,and both preclinical and clinical data have suggested it has great potential inthe treatment of BRCA-mutated cancers. This agent has subsequently beenlicensed by Pfizer to Clovis Oncology who are now actively developing it in anumber of cancer indications," the spokesman tells DDNEWS.
Clovis has three product candidates in its developmentpipeline for which the company holds global rights. In addition to rucaparib,there is CO-1686, an orally available epidermal growth factor receptor (EGFR)covalent inhibitor currently in Phase I/II development for the treatment ofnon-small cell lung cancer (NSCLC), in patients with initial activating EGFRmutations, as well as the T790M dominant resistance mutation. The third productcandidate, currently in the discovery phase, is a novel cKIT inhibitortargeting resistance mutations for the treatment of gastrointestinal stromaltumors.