On July 16, 2014 Immunocore and Eli Lilly reported they have entered into a co-discovery and co-development collaboration to research and potentially develop novel T cell-based cancer therapies (Press release Immunocore, JUL 16, 2014, View Source [SID:1234500630]).

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Using Immunocore’s Immune Mobilising Monoclonal T-Cell Receptor Against Cancer (ImmTAC) technology, the companies will seek to use the power of the body’s own immune system to attack cancer cells. ImmTACs have shown potential to direct a patient’s T cells to specifically target the cancerous cells, avoiding damage to healthy cells.

Under the terms of the agreement, Immunocore will receive an upfront fee of $15 million per program for the discovery of novel ImmTACs against jointly-selected cancer targets in order to generate preclinical candidate packages. If Lilly accepts a preclinical candidate package to develop and potentially commercialize, Immunocore will receive an opt-in fee of $10 million and will have an option to continue co-development with Lilly on a cost-sharing and profit-sharing basis. If Immunocore does not exercise its option, it will be entitled to potential future significant milestone and royalty payments.

"We are very pleased to have entered into this strategic partnership with Lilly, and look forward to working together in an integrated fashion," said Eva-Lotta Allan, Chief Business Officer, Immunocore. She added: "Lilly is a leading oncology player and we are delighted to advance novel T cell-based therapies into the clinic in collaboration with them."

"The major goal and challenge of cancer immunotherapy is to direct the immune system to recognize and destroy cancer. We believe Immunocore’s ImmTAC platform has the potential to do just that," said Jan Lundberg, Ph.D., Executive Vice President, Science and Technology and President, Lilly Research Laboratories. "We are delighted to be working closely with Immunocore to develop potential novel therapies for cancer patients."

On July 17, 2014 GlaxoSmithKline reported that the Independent Data Monitoring Committee (IDMC) recommended COMBI-v (MEK116513), a phase III study of its MEK inhibitor, trametinib (Mekinist), in combination with its BRAF inhibitor, dabrafenib (Tafinlar), compared to vemurafenib in patients with BRAF V600E or V600K mutation-positive unresectable or metastatic cutaneous melanoma be stopped early (Press release GlaxoSmithKline, JUL 16, 2014, View Source;mekinist–and-dabrafenib–tafinlar–combination-demo.html [SID:1234500631]). This IDMC recommendation is based on an interim analysis which demonstrated an overall survival benefit for the trametinib and dabrafenib combination compared to vemurafenib that crossed the pre-specified efficacy stopping boundary. The safety profile of the trametinib and dabrafenib arm was consistent with the safety profile of the combination observed to date.

The IDMC recommendation today is based on headline data; further analysis of safety and efficacy data is underway and will be completed in the coming months. Eligible study patients who were randomised to the vemurafenib arm will be allowed to cross over to receive treatment with the trametinib and dabrafenib combination.

Dr. Rafael Amado, Head of Oncology R&D at GSK, said: “Today’s headline results for the combination of dabrafenib and trametinib add to the body of evidence our phase III program has provided thus far, which we hope will more fully characterise the efficacy and safety profile of this combination for patients with BRAF V600-mutant metastatic melanoma. We will continue to analyse this data versus vemurafenib over the coming months and look forward to sharing these with the scientific community once the analysis is complete.”

About COMBI-v
This phase III, randomised, open-label study compared the combination of dabrafenib and trametinib to vemurafenib in subjects with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma. COMBI-v enrolled 704 patients from investigative sites in the U.S., Europe, Canada, Russia, Ukraine, Israel, Argentina, Brazil, Korea, New Zealand, Taiwan, and Australia.

The primary objective of the study was to evaluate dabrafenib and trametinib combination therapy vs. vemurafenib with respect to OS. Secondary objectives evaluated and compared dabrafenib and trametinib combination therapy versus vemurafenib with respect to progression-free survival, overall response rate, and duration of response. The safety of dabrafenib and trametinib combination therapy, including incidences of squamous cell carcinoma and other proliferative skin diseases, was also evaluated.

On July 15, 2014 Roche reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Avastin (bevacizumab) plus chemotherapy for the treatment of women with persistent, recurrent or metastatic cervical cancer (Press release Hoffmann-La Roche, JUL 14, 2014, View Source [SID:1234500629]).

“This regulatory application for Avastin is important because chemotherapy is the only approved treatment for women with metastatic, recurrent or persistent cervical cancer,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Treatment with Avastin plus chemotherapy may help women with these conditions live longer than chemotherapy alone, and we look forward to working with the FDA on potentially making this medicine available to patients.”

The designation of Priority Review status is granted to medicines that the FDA believes have the potential to provide “significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.” The sBLA for Avastin plus chemotherapy in persistent, recurrent or metastatic cervical cancer is based on data from the Phase III GOG-0240 trial with an FDA action date of October 24, 2014.

About the GOG-0240 study
GOG-0240 is an independent, National Cancer Institute (NCI)-sponsored Phase III study which assessed the efficacy and safety profile of Avastin plus chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) in women with persistent, recurrent, or metastatic cervical cancer. Study data from 452 women showed:

The study met its primary endpoint of improving overall survival (OS) with a statistically significant 29 percent reduction in the risk of death for women who received Avastin plus chemotherapy compared to those who received chemotherapy alone (median OS: 17.0 months vs. 13.3 months; Hazard Ratio (HR)=0.71, p=0.004).
Women in the Avastin plus chemotherapy arm also lived longer without disease worsening (progression free survival, PFS) compared to those who received chemotherapy alone (median PFS: 8.2 months vs. 5.9 months; HR=0.67, p=0.002).
Hypertension (high blood pressure) of Grade 2 or higher was significantly more common with Avastin-containing regimens (25 percent vs. 2 percent), but no patients discontinued Avastin because of hypertension. Gastrointestinal or genitourinary fistulas (abnormal passage from one part of the body to another) of Grade 3 or higher were significantly increased with the Avastin-containing regimens (6 percent vs. 0 percent), as were thromboembolic events (blood clots) of Grade 3 or higher (8 percent vs. 1 percent). There was no increase in treatment-related deaths in the Avastin plus chemotherapy arm as compared to the chemotherapy alone arm.

On July 14, 2014 ARIAD Pharmaceuticals reported that the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has provided the Company with a request for limited additional information regarding Iclusig (ponatinib) as part of its ongoing review under the Article 20 referral procedure (Press release Ariad, JUL 14, 2014, View Source [SID:1234500626]). The PRAC has requested further information regarding proposed dose modifications after achievement of a response and patient monitoring and details concerning a risk management plan. Following ARIAD’s response and input from the agency’s Scientific Advisory Group, the Company expects that the PRAC will complete its review and make final recommendations to the Committee for Medicinal Products for Human Use (CHMP) at its meeting in October 2014.

“As we finalize our recommendations on dose modifications of Iclusig and response monitoring of patients, we will work closely with the European regulatory agency and its expert advisors so that CML patients and their treating physicians have the best guidance available supporting the appropriate use of Iclusig,” said Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD.

In March 2014 ARIAD submitted responses to initial questions outlined by the PRAC as part of the Article 20 process, which was initiated in December of last year, and responses to a second set of questions were submitted to the PRAC in June.

On July 14, 2014 Roche reported that the Phase III coBRIM study (NCT01689519) met its primary endpoint (Press release Hoffmann-La Roche, JUL 13, 2014, View Source [SID:1234500628]). The study demonstrated that the investigational MEK inhibitor cobimetinib, used in combination with Roche’s BRAF inhibitor Zelboraf, helped patients with previously untreated BRAF V600 mutation-positive advanced melanoma live significantly longer without their disease worsening (progression-free survival; PFS) compared to Zelboraf alone. Adverse events were consistent with those observed in a previous study of the combination.

“Despite great progress in our understanding and therapy in recent years, advanced melanoma remains a difficult and deadly disease that requires more treatment options,” said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. “These encouraging data support the potential combined use of cobimetinib with Zelboraf to block tumour growth longer than Zelboraf alone. We hope this combination therapy will lead to a new option for patients.”

Data from this pivotal study will be presented at an upcoming medical meeting. Additionally, Roche plans to submit these data to the U.S. Food and Drug Administration, European Medicines Agency, and other health authorities around the world for potential approval.

Cobimetinib is designed to selectively block the activity of MEK,2 one of a series of proteins inside cells that make up a signaling pathway that helps regulate cell division and survival. Cobimetinib binds to MEK while Zelboraf binds to mutant BRAF, another protein on the pathway, to interrupt abnormal signaling that can cause tumours to grow.
About the coBRIM study

CoBRIM is an international, randomised, double-blind, placebo-controlled Phase III study evaluating the safety and efficacy of cobimetinib in combination with Zelboraf, compared to Zelboraf alone, in 495 patients with BRAF V600 mutation-positive unresectable locally advanced or metastatic melanoma, previously untreated for advanced disease.6 The primary endpoint for coBRIM is PFS. Secondary endpoints include overall survival, objective response rate, duration of response and other safety, pharmacokinetic and quality of life measures.

The coBRIM study used the Roche cobas 4800 BRAF Mutation Test to determine eligibility of patients for the study. This test identifies people whose tumours carry the BRAF V600 mutation, and therefore, patients who are most appropriate to receive this combination of treatments.