The drug, RG7813, delivers a cytokine (engineered IL2) to a specific part of the carcinoembryonic antigen (CEA) protein which is exposed only on the surface of cancer cells, resulting in a narrowly-targeted treatment (Press release Cancer Research UK, MAR 27, 2014, View Source [SID:1234500343]).
Cancer Research Technology, the commercial arm of Cancer Research UK, licensed the monoclonal antibody called PR1A3 to Roche. PR1A3 was discovered in Sir Walter Bodmer’s laboratory when he was director of the Imperial Cancer Research Fund. Roche has subsequently engineered the antibody and incorporated it into its proprietary immunocytokine drug platform to generate the final drug candidate. Clinical trials have then been initiated.
It is in a Phase I study for the treatment of solid tumors (Filing Annual 2013, Hoffmann-La Roche, JAN 30, 2014, View Source [SID:1234500028]). Design: Single and multiple dose escalation study with extension cohorts. Primary endpoint: Safety, PK, PD. Number of patients: 110.
It was previously licensed to Antisoma; however, this agreement was terminated (Company prospectus, Antisoma, DEC 1998; Direct communication, CRT, MAY 2008).

On March 26, 2014 GlaxoSmithKline reported that it has withdrawn its Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for the use of Mekinist (trametinib) in combination with the previously approved BRAF inhibitor Tafinlar (dabrafenib) for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation (Press release GlaxoSmithKline, MAR 26, 2014, View Source;combined-use-of-mekinist–trametinib–and-taf.html [SID:1234500335]). The application for the use of Mekinist as a single agent in the same patient population, submitted simultaneously with the MAA for the combination, is still undergoing review by the EMA.
The Committee for Medicinal Products for Human Use (CHMP) of the EMA has indicated that the data provided to date by GSK did not allow the Committee to conclude on a positive benefit-risk balance of the combination. GSK intends to re-submit the MAA for the combined use of Tafinlar and Mekinist when additional data from the ongoing Phase III programme become available.
The regulatory submission for the combination was based on the results from an open-label randomised three-arm phase II study, provided to EMA in 2012. The study aimed to assess the safety and efficacy of dabrafenib in combination with two different doses of trametinib compared to dabrafenib monotherapy in patients with unresectable or metastatic BRAF V600 E or K mutation-positive melanoma.
Additional data from the randomised, double-blind Phase III study (COMBI-d) comparing the combination of dabrafenib and trametinib to dabrafenib and placebo as first-line therapy in the same patient population were also provided to EMA earlier this year.

On March 25, 2014 Exelixis reported that the European Commission has approved COMETRIQ (cabozantinib) for the treatment of adult patients with progressive, unresectable locally advanced or metastatic medullary thyroid carcinoma (MTC) (Press release Exelixis, MAR 25, 2014, View Source [SID:1234500329]). The European Commission granted conditional marketing authorization following a positive opinion from the European Committee for Medicinal Products for Human Use (CHMP) issued in December 2013. Similar to another drug approved in this setting, the approved indication states that for patients in whom Rearranged during Transfection (RET) mutation status is not known or is negative, a possible lower benefit should be taken into account before individual treatment decisions.
Additionally, the Committee for Orphan Medicinal Products (COMP) during its January 2014 meeting reviewed the designation for COMETRIQ (cabozantinib) as an orphan medicinal product for the treatment of medullary thyroid carcinoma and recommended maintenance of orphan drug designation at the time of marketing authorization.
The U.S. Food and Drug Administration approved COMETRIQ for the treatment of progressive, metastatic MTC in the United States on November 29, 2012. The approvals of COMETRIQ in both the United States and the European Union were based on data from EXAM, the international, multi-center, randomized double-blinded controlled phase 3 clinical trial conducted in 330 patients with progressive, unresectable locally advanced or metastatic MTC, in which cabozantinib met its primary efficacy endpoint of improving progression-free survival (PFS) as compared to placebo. Please see Important Safety Information for COMETRIQ, including Boxed Warnings, below.
Pursuant to the terms of a commercialization and distribution agreement between Exelixis and Swedish Orphan Biovitrum (Sobi) signed in February 2013, Sobi will support the commercialization of COMETRIQ in the European Union for the approved indication through the end of 2015.