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FDA Approval for Vectibix & Companion Diagnostic; Breakthrough Status for Elotuzumab & CO-1686

doi: 10.1097/01.COT.0000451730.95667.73
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The U.S. Food and Drug Administration has approved Vectibix (panitumumab) for use in combination with FOLFOX as first-line treatment for patients with wild-type KRAS metastatic colorectal cancer. The FDA has also approved the therascreen KRAS RGQ PCR Kit (therascreen KRAS test), made by Qiagen N.V., as a companion diagnostic for Vectibix (which detects the most frequent mutations in the KRAS gene).

Vectibix is a fully human anti-EGFR antibody, which had previously been approved for the treatment of patients with EGFR-expressing metastatic colorectal cancer after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy (OT 12/10/06 issue).

This most recent indication for the drug makes Vectibix the first and only biologic therapy indicated for the use with FOLFOX in first-line treatment for the treatment of patients with metastatic colorectal cancer with the wild-type KRAS mutation.

The approval for Vectibix, which is manufactured by Amgen, is based on results from two Phase III studies. The PRIME Phase III study showed that for patients with wild-type KRAS tumors in exon two achieved significant improvements in progression-free survival with Vectibix and FOLFOX compared with use of FOLFOX alone (9.6 months vs. 8 months), as well as a significant improvement in overall survival (23.8 months for the combination vs. 19.4 months for FOLFOX alone).

Also, the Phase III ASPECCT trial met its primary endpoint of non-inferiority for improving overall survival in patients taking Vectibix compared with patients taking cetuximab as a single agent for the treatment of metastatic colorectal cancer in patients with wild-type KRAS tumors who had not responded to chemotherapy.

The most common adverse reactions of Vectibix are skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea. The most frequently reported serious, adverse reactions of Vectibix are general physical health deterioration, and intestinal obstruction.

In other recent FDA actions, both elotuzumab and CO-1686 were given Breakthrough Therapy status—elotuzumab for patients with multiple myeloma who have received one or more prior therapies; and CO-1686 for second-line treatment of patients with the T790M mutation with epidermal growth factor receptor mutant non-small cell lung cancer.

The designation, enacted as part of the FDA's 2012 Safety and Innovation Act, was created to expedite the development and review time of a potential new drug for serious or life-threatening disease where early clinical evidence suggests the drug may demonstrate substantial improvement compared with existing therapies.

Elotuzumab—being co-developed with AbbVie, with Bristol-Myers Squibb leading the commercialization of the agent—is an investigational monoclonal antibody targeted against Signaling Lymphocyte Activation Molecule (SLAMF7, also called CS1), a glycoprotein expressed on myeloma and natural killer cells, but that is not detectable in normal tissue.

Elotuzumab's breakthrough designation is based on findings from a randomized Phase II, open-label study that evaluated two dose levels of the drug in combination with lenalidomide and low-dose dexamethasone in previously treated patients with multiple myeloma. Phase III trials for the drug are now ongoing as first-line treatment (ELOQUENT-1), as well as in relapsed or refractory disease (ELOQUENT-2).

CO-1686, made by Clovis Oncology, is a novel, oral, targeted covalent inhibitor of EGFR designed to selectively target both the initial activation EGFR mutation as well as the T790M resistance mutation, while sparing wild-type EGFR at anticipated therapeutic doses.

The Breakthrough Therapy designation is based on interim data from an ongoing Phase I/II study of the drug; additional results from the trial were presented at the ASCO Annual Meeting (Abstract 2524).

© 2014 by Lippincott Williams & Wilkins, Inc.
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