Foundation Medicine has teamed up with Clovis Oncology to develop a biomarker-based in vitro diagnostic to help select patients most likely to respond to Clovis’ anticancer candidate rucaparib, a PARP inhibitor currently undergoing Phase I/II clinical development. The collaboration aims to identify mutations other than germline and somatic BRCA alterations, which may represent new tumor targets for rucaparib.

Rucaparib is an orally-available, small molecule PARP inhibitor in development for the treatment of patients with cancers predisposed to PARP inhibitor sensitivity. The drug has undergone testing in multiple Phase I and Phase II studies as both an oral and IV formulation, primarily in combination with cytotoxic chemotherapy. While Clovis’ initial focus is on developing rucaparib for ovarian and breast cancers with defective BRCA function, the firm claims its partnership with Foundation Medicine could identify new targets for the drug. This could feasibly increase the proportion of, for example, ovarian cancer patients who are eligible for rucaparib therapy from the 15% or so who have germline BRCA mutations, to an estimated 40–50% of patients who exhibit DNA repair deficiencies caused by somatic mutations in other genes.

“Foundation Medicine’s leadership in next-generation sequencing and genomic analysis make them an ideal partner to work with us on our rucaparib program,” comments Clovis president and CEO Patrick J. Mahaffy. “This continues our commitment to developing targeted therapies with companion diagnostics to identify the patients most likely to benefit from our therapeutics.”

Clovis’ lead anticancer candidate, CO-101, is a lipid-drug conjugate of gemcitabine, which is in development initially for treating pancreatic cancer patients with tumors that express low amounts of a membrane transporter protein known as hENT1, and are thus expected to be resistant to standard gemcitabine-based therapy. CO-101 is designed to enter cells by a mechanism that is independent of hENT1 expression to overcome this resistance mechanism. The drug is currently undergoing a pivotal study, Leap (Low hENT1 and Adenocarcinoma of the Pancreas), topline data from which are expected during Q4 2012.

Clovis’ CO-1686 candidate is an oral-targeted covalent (irreversible) inhibitor of cancer-related mutant forms of EGFR. The drug is currently undergoing Phase I/II development for the treatment of non-small cell lung cancer (NSCLC). CO-1686 is designed to selectively target both the initial activating EGFR mutations as well as the T790M resistance mutation, without impacting on normal EGFR at anticipated therapeutic doses. The firm says it plans to develop CO-1686 for both second-line therapy against EGFR-mutated NSCLC that has become resistant to EGFR-directed therapy due to the emergence of the T790M secondary mutation, and also potentially as a first-line treatment for EGFR-mutated NSCLC.

Cancer diagnostics firm Foundation Medicine’s initial clinical product, FoundationOne™, is a one-for-all tumor profiling test designed to assess a patient’s genetic background and aid physicians and clinicians in selecting the most appropriate targeted therapies and clinical trials. The test evaluates all classes of genomic alterations including copy number alterations, insertions, deletions, and rearrangements, in hundreds of cancer-related genes. Foundation Medicine claims the test represents the first commercially available targeted sequencing assay to use clinical-grade next-generation sequencing in routine cancer specimens.

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