On December 24, 2014, Genentech reported that the U.S. Food and Drug Administration (FDA) approved a supplemental biologics license application (sBLA) for Gazyva in combination with chlorambucil chemotherapy in people with previously untreated chronic lymphocytic leukemia (CLL) (Press release Genentech, DEC 24, 2014, View Source [SID:1234501261]). The sBLA adds to the label data from Stage 2 of the CLL11 study showing significant improvements with Gazyva plus chlorambucil across multiple clinical endpoints when compared head-to-head with Rituxan (rituximab) plus chlorambucil.

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The approval includes complete response (CR) and minimal residual disease (MRD) data from Stage 2 of the study. Additionally, overall survival (OS) data was added from Stage 1 of the study comparing Gazyva plus chlorambucil to chlorambucil alone.

"Gazyva is the first and only medicine to significantly help people live without their disease worsening when combined with chlorambucil compared to Rituxan and chlorambucil in people with previously untreated chronic lymphocytic leukemia," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "These new data enhance our understanding of the disease and its treatment, and this approval affirms an important treatment option for people with this difficult-to-treat disease."

The sBLA approval updated the Gazyva prescribing information with the following data:

Gazyva plus chlorambucil helped people with previously untreated CLL live nearly a year longer without their disease worsening or death (progression-free survival; PFS) than Rituxan plus chlorambucil (median PFS: 26.7 months vs. 14.9 months, respectively. HR=0.42, 95 percent CI 0.33-0.54, p<0.0001).
Gazyva plus chlorambucil nearly tripled the number of people showing no evidence of disease (CR) compared to Rituxan plus chlorambucil (26.1 percent vs. 8.8 percent, respectively).
Of the people who achieved a complete response with or without complete recovery from abnormal blood cell counts (CR, CRi), 19 percent (18/94) of people in the Gazyva arm compared to 6 percent (2/34) of people in the Rituxan arm were MRD negative in the bone marrow, and 41 percent (39/94) of people in the Gazyva arm compared to 12 percent (4/34) people in the Rituxan arm were MRD negative in the peripheral blood. MRD negative means no residual traces of the cancer were found.
Data from the first stage of the CLL11 study showed that at nearly two years, the rate of death was 9 percent (22/238) for people who received Gazyva plus chlorambucil compared to 20 percent (24/118) for those who received chlorambucil alone (HR=0.41, 95 percent CI 0.23-0.74). The median OS has not yet been reached.

Gazyva can cause serious or life-threatening side effects including: Hepatitis B reactivation, progressive multifocal leukoencephalopathy (PML), infusion reactions, tumor lysis syndrome, infections, and low white blood cell counts. The most common side effects of Gazyva are infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.

Gazyva, the first medicine approved with the FDA’s Breakthrough Therapy Designation, was approved for use in combination with chlorambucil in people with previously untreated CLL on November 1, 2013. Gazyva, known as Gazyvaro in Europe, was approved by the European Commission for the same indication in July 2014. Gazyva is also being investigated in a broad development program across various types of blood cancers, including multiple Phase III studies in non-Hodgkin’s lymphoma (NHL).

About the CLL11 Study

CLL11 is a Phase III, multicenter, open-label, randomized three-arm study, conducted in cooperation with the German CLL Study Group, in 781 previously untreated people with CLL and co-existing medical conditions. Stage 1 (n=589) compared Gazyva plus chlorambucil to chlorambucil alone and Rituxan plus chlorambucil to chlorambucil alone. Stage 2 (n=663) compared Gazyva plus chlorambucil directly with Rituxan plus chlorambucil. The primary endpoint of the study was PFS with secondary endpoints including overall response rate (ORR), OS, CR, median duration of response, MRD and safety profile. Results from Stage 2 and updated data from Stage 1 were presented in 2013 during the Plenary Scientific Session of the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting and published in the New England Journal of Medicine in 2014.

On December 23, 2014 Elios Therapeutics, LLC reported it received FDA approval of its Investigational New Drug (IND) application and its randomized phase IIb trial planned to enroll 120 stage III and IV (resected) melanoma patients to assess the ability of a personalized vaccine to prevent recurrence (Press release, Orbis Health Solutions, DEC 23, 2014, View Source [SID1234532480]). The trial will be conducted at a dozen leading academic cancer research hospitals in the United States.

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The Elios melanoma vaccine to be assessed in this pivotal trial will deliver personalized immunotherapy developed from the patient’s cancer cells and dendritic cells to create a specific immune response in hopes of destroying any remaining cancer cells after surgery and thereby prevent recurrence of melanoma and improve overall survival rates. Qualifying trial patients must be in stage III or IV and considered disease-free after definitive surgery and completion of standard of care therapies.

"The Elios vaccine has shown effectiveness in metastatic patients, and delivered even more promising results in the adjuvant setting. Further, the vaccine has the safety profile to allow for treatment in a preventive setting," explains George E. Peoples, MD, FACS and Chief Medical Officer, Elios Therapeutics, LLC. "Stage III and IV melanoma patients do not currently have an option for a safe, non-toxic, and effective adjuvant therapy. Melanoma at this stage recurs at an approximately 60-70 percent rate in two years, and once that happens, patients will very likely succumb to their disease. We believe that our vaccine technology can cut that rate significantly, preventing recurrence and death."

The Elios Therapeutics’ prospective, randomized, double-blind trial (NCT#02301611) is enrolling patients now, and it is anticipated that all 12-15 sites, to include the lead site at John Wayne Cancer Institute in Santa Monica, California, will open early in 2015. The trial is expected to conclude in 2018.

The vaccine being studied was developed by Elios Therapeutics’ Thomas Wagner, PhD.

"Our approach is completely different than others, in that we don’t need to identify a specific mutation or create a new drug to treat each type of cancer," explains Dr. Wagner. "This vaccine utilizes a particular patient tumor’s unique antigenic and molecular profile and a novel delivery mechanism to set the immune system to defeat that patient’s disease. Our therapy is applicable to any patient, with any tumor.

"The adjuvant therapies available for melanoma today to prevent recurrence are highly toxic and largely ineffective. We believe our vaccine has the potential to make a real impact in this setting by targeting and killing remaining metastatic cells without causing any dangerous side effects," says Dr. Wagner.

On December 22, 2014 Cancer Research UK, Cancer Research Technology (CRT) and Amgen Inc., reported that they have reached an agreement to take forward Amgen’s experimental immunotherapy treatment, AMG319, into its first trial involving patients with solid tumours, following a successful phase one trial of this drug in leukaemia and lymphoma patients (Press release, Cancer Research Technology, 22 22, 2014, View Source [SID1234523243]).

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The collaboration forms part of Cancer Research UK’s Clinical Development Partnership (CDP) scheme, a joint initiative between Cancer Research UK’s Centre For Drug Development (CDD) and CRT, to develop promising anti-cancer agents for which pharmaceutical companies do not have the resource to progress through early phase clinical trials.

AMG319 targets an important protein called P13 kinase delta to disable the ‘cloaking device’ that tumours use to evade detection by the immune system.

Studies in mice with solid tumours, part-funded by Cancer Research UK, have shown the ability of this class of drug to mount a response against cancer cells by independently stimulating the immune system but this is the first time it has been trialled in patients with solid tumours.*

Cancer Research UK’s Centre for Drug Development will manage and sponsor the study through the Experimental Cancer Medicine Centre (ECMC) network, with the aim of evaluating the safety and biological effect of AMG319 in patients with head and neck cancer.

Dr Jeremy Haigh, Chief Operating Officer for Amgen’s European R&D Organisation, said: "We fully recognise the value of working with Cancer Research UK in this project. Its distinctive expertise and resources will make a big contribution to our deeper understanding of this area of cancer treatment and wider understanding of AMG319. Cancer Research UK brings more than a century of experience in the prevention, diagnosis and treatment of cancer. "

Dr Nigel Blackburn, Cancer Research UK’s Director of Drug Development, said: "We’re pleased that this collaboration will allow patients with a wider variety of cancers to access this promising new immunotherapy treatment, which was originally developed for blood cancer patients. Treatments that train the immune system to recognise and kill cancer cells are showing huge promise, so we look forward to seeing whether this drug could echo those results."

On December 22, 2014 Cancer Research UK, Cancer Research Technology (CRT) and Amgen Inc. reported an agreement to take forward Amgen’s experimental immunotherapy treatment, AMG319, into its first trial involving patients with solid tumours, following a successful phase one trial of this drug in leukaemia and lymphoma patients (Press release, Cancer Research Technology, DEC 22, 2014, View Source [SID1234523214]).

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The collaboration forms part of Cancer Research UK’s Clinical Development Partnership (CDP) scheme, a joint initiative between Cancer Research UK’s Centre For Drug Development (CDD) and CRT, to develop promising anti-cancer agents for which pharmaceutical companies do not have the resource to progress through early phase clinical trials.

AMG319 targets an important protein called P13 kinase delta to disable the ‘cloaking device’ that tumours use to evade detection by the immune system.

Studies in mice with solid tumours, part-funded by Cancer Research UK, have shown the ability of this class of drug to mount a response against cancer cells by independently stimulating the immune system but this is the first time it has been trialled in patients with solid tumours.*

Cancer Research UK’s Centre for Drug Development will manage and sponsor the study through the Experimental Cancer Medicine Centre (ECMC) network, with the aim of evaluating the safety and biological effect of AMG319 in patients with head and neck cancer.

Dr Jeremy Haigh, Chief Operating Officer for Amgen’s European R&D Organisation, said: "We fully recognise the value of working with Cancer Research UK in this project. Its distinctive expertise and resources will make a big contribution to our deeper understanding of this area of cancer treatment and wider understanding of AMG319. Cancer Research UK brings more than a century of experience in the prevention, diagnosis and treatment of cancer. "

Dr Nigel Blackburn, Cancer Research UK’s Director of Drug Development, said: "We’re pleased that this collaboration will allow patients with a wider variety of cancers to access this promising new immunotherapy treatment, which was originally developed for blood cancer patients. Treatments that train the immune system to recognise and kill cancer cells are showing huge promise, so we look forward to seeing whether this drug could echo those results."

On December 22, 2014 Kite Pharma reported that the Company has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) to conduct a Phase 1/2 study of KTE-C19, the Company’s investigational anti-CD19 CAR T cell therapy, for the treatment of patients with refractory aggressive non-Hodgkin lymphoma (NHL) (Press release Kite Pharma, DEC 22, 2014, View Source [SID:1234501230]).

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