Roche provides update on phase III study of onartuzumab in people with specific type of lung cancer

Roche  announced  that an independent data monitoring committee has recommended that the phase III METLung study be stopped due to a lack of clinically meaningful efficacy.

The study evaluated if onartuzumab (MetMab) in combination with Tarceva (erlotinib) helped patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose tumours were identified as MET-positive live longer compared to Tarceva alone. Overall adverse event rates were generally similar between the two groups. Data will be submitted for presentation at a forthcoming medical meeting.

« These results are disappointing because new options are needed for patients with lung cancer, the most common and deadly cancer worldwide,” said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. « We remain committed to helping patients with lung cancer and are studying several investigational medicines in this disease.”

Roche is evaluating the implications of the METLung study results across the ongoing onartuzumab clinical programme.

About the METLung Study (NCT01456325)

  • METLung is a Phase III, randomised, double-blind study evaluating the efficacy and safety profile of onartuzumab in combination with Tarceva in patients with previously treated (second- or third-line) advanced NSCLC identified to be MET-positive. The METLung study included a companion diagnostic immunohistochemistry (IHC) test that was co-developed with Ventana Medical Systems, Inc., a member of the Roche Group.
  • Four hundred and ninety-nine patients were randomized to receive 150 mg of Tarceva taken daily plus either:
    • Intravenous 15 mg/kg of onartuzumab every three weeks
    • Intravenous placebo every three weeks
  • The primary endpoint is overall survival. Secondary endpoints include progression-free survival, objective response rate and safety profile.
  • The results announced today are from a pre-specified interim analysis.

About Lung Cancer

According to the World Health Organization, it is estimated that nearly 1.6 million people worldwide died of lung cancer in 2012; NSCLC accounts for 85 percent of all lung cancers.

About the MET Pathway

MET is a protein found on the surface of cells and acts as a receptor that binds to another protein called Hepatocyte Growth Factor (HGF), also known as « Scatter Factor ». When HGF binds to MET, it causes MET proteins to form pairs (dimerise), which triggers a signalling cascade that tells cells to grow, divide, and spread to other parts of the body. Activation of the MET pathway has been proposed as a mechanism of tumour growth and spread (metastasis).

About Onartuzumab

Onartuzumab, an investigational monovalent (one-armed) monoclonal antibody designed to specifically target the MET receptor, is being studied in various cancers.

 

Source: Roche

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Roche’s Kadcyla approved in the EU for advanced HER2-positive breast cancer

Roche announced that Kadcyla (trastuzumab emtansine or T-DM1), the latest targeted medicine from its HER2 franchise and its first antibody-drug conjugate, has been approved by the European Commission for people with previously treated HER2-positive advanced breast cancer.

Specifically, Kadcyla is indicated as a single agent for the treatment of adults with HER2-positive, unresectable locally advanced or metastatic breast cancer who previously received Herceptin (trastuzumab) and a taxane, separately or in combination. The indication also stipulates that those treated should either have received prior therapy for locally advanced or metastatic disease, or have had disease recurrence during or within six months of completing adjuvant therapy.

“Kadcyla’s approval in the EU is important because this type of targeted medicine has been shown in clinical studies to offer clear benefits for people with advanced HER2-positive breast cancer,” said Hal Barron, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Now that Kadcyla has been approved, we can begin discussions with the relevant EU reimbursement authorities to ensure that people who need this medicine can receive it as quickly as possible. »

The decision is based on results from the pivotal Phase III EMILIA study in which people previously treated with Herceptin and a taxane for their HER2-positive advanced breast cancer were randomised to receive either Kadcyla or a standard treatment, lapatinib and Xeloda (capecitabine). People receiving Kadcyla survived significantly longer than those who received lapatanib and Xeloda (30.9 vs 25.1 months) and also lived for nearly 10 months (9.6 months) without their disease getting worse, a median of 3.2 months longer than those who received lapatinib and Xeloda. They also experienced fewer of the severe side effects commonly associated with chemotherapy, as Kadcyla’s targeted mode of action works to deliver the treatment directly to cancer cells, limiting damage to healthy tissues.

 

Source: Roche

Roche Cancer Vaccine Pact Could Net Immatics $1B

Roche will oversee clinical development and commercialization of all immunotherapies generated by immatics biotechnologies under a cancer vaccine and immunotherapy collaboration that could net the German clinical-stage biopharma more than $1 billion.

Roche agreed to pay immatics $17 million up-front and additional unspecified committed research funding, plus more than $1 billion in milestone payments and royalties across three cancer indications, to be based on sales of the cancer vaccines and immunotherapies resulting from the companies’ collaboration.

The collaboration will focus on research, clinical development, and commercialization of a number of new tumor-associated peptide (TUMAP)-based cancer vaccine candidates and other immunotherapies in oncology, targeting primarily gastric, prostate, and non-small cell lung cancer. Furthest along in development among the candidates is IMA942, for gastric cancer, which according to the companies is ready for Phase I trials.

Also as part of the collaboration, immatics will use its XPRESIDENT® technology platform to identify TUMAP candidates for development of cancer vaccines and other compounds targeting cancer peptide antigens, primarily in gastric, prostate, and non-small cell lung cancer. According to the companies, XPRESIDENT is the only known high-throughput research technology capable of directly identifying, quantifying, and prioritizing cancer antigens recognized by T lymphocytes based on the ability of the immune system to detect them.

“The wealth of relevant cancer-specific antigens that we expect to emerge from this research collaboration will provide an extraordinary opportunity to elicit broad tumor-specific immune responses upon vaccination, especially when combined with other immunomodulatory molecules in our pipeline,” Hy Levitsky, Roche’s head of cancer immunology experimental medicine, said in a statement. “Discovery of novel antigens also will provide unique targets for other protein-based anti-cancer agents currently under development.”

immatics’ collaboration with Roche comes about a month after the company won €34 million ($46 million) in Series D financing—of which €12 million ($16 million) will be received immediately—to conclude development of its lead vaccine IMA901, now in a Phase III trial, including completing all activities needed to prepare for regulatory filings in the United States and Europe.

IMA901 is a cancer vaccine consisting of 10 TUMAPs found to be highly overexpressed in the majority of patients suffering from renal cell carcinoma (RCC). The vaccine has U.S. and European orphan drug designations for treating RCC in HLA-A*02 positive patients. The Phase III trial is designed to evaluate overall survival with IMA901 in combination with Pfizer ‘s Sutent® (sunitinib), the current standard first-line therapy, compared with sunitinib alone in patients with metastatic and/or locally advanced RCC. A total of 339 patients are enrolled in the trial, which is expected to generate interim overall survival results in 2014, with final data in 2015.

Source : genengnews

FDA approves Roche’s Kadcyla (trastuzumab emtansine), the first antibody-drug conjugate for treating HER2-positive metastatic breast cancer

New personalised medicine helped people in Phase III study live longer, compared to standard treatment

Roche  announced that the U.S. Food and Drug Administration (FDA) has approved Kadcyla (trastuzumab emtansine or T-DM1) for the treatment of people with HER2-positive metastatic breast cancer (mBC) who have received prior treatment with Herceptin (trastuzumab) and a taxane chemotherapy. Kadcyla is the fourth medicine from Roche to receive FDA approval for people with advanced cancers within the past two years.

An antibody-drug conjugate (ADC) is a new kind of targeted cancer medicine that can attach to certain types of cancer cells and deliver chemotherapy directly to them. Kadcyla is the first FDA-approved ADC for treating HER2-positive mBC, an aggressive form of the disease.

“Kadcyla is an antibody-drug conjugate representing a completely new way to treat HER2-positive metastatic breast cancer, and it helped people in the EMILIA study live nearly six months longer,” said Hal Barron, M.D., Roche’s Chief Medical Officer and Head, Global Product Development. “We currently have more than 25 antibody-drug conjugates in our pipeline and hope this promising approach will help us deliver more medicines to fight other cancers in the future.”

Kadcyla is made up of the antibody, trastuzumab, and the chemotherapy, DM1, joined together using a stable linker. Kadcyla combines the mechanisms of action of both trastuzumab and DM1, and it is the first Roche ADC approved by the FDA. Roche has studied ADC science for more than a decade and has eight ADCs in Phase I or Phase II studies for different types of cancer.

Roche has also submitted a Marketing Authorisation Application to other Regulatory Authorities around the world, including the European Medicines Agency (EMA), for Kadcyla for the treatment of people with HER2-positive mBC. This application is currently under review by the EMA.

Kadcyla efficacy in HER2-positive mBC

The FDA approval of Kadcyla is based on results from EMILIA (TDM4370g/BO21977), an international, Phase III, randomised, open-label study comparing Kadcyla alone to lapatinib in combination with Xeloda (capecitabine) in 991 people with HER2-positive locally advanced breast cancer or mBC who had previously been treated with Herceptin and a taxane chemotherapy. Results include:1

  • The study met both co-primary efficacy endpoints of overall survival and progression-free survival (PFS; as assessed by an independent review committee).
  • People who received Kadcyla lived a median of 5.8 months longer (overall survival) than those who received the combination of lapatinib and Xeloda, the standard of care in this setting (median overall survival: 30.9 months vs. 25.1 months).
  • People receiving Kadcyla experienced a 32 percent reduction in the risk of dying compared to people who received lapatinib and Xeloda (HR=0.68; p=0.0006).
  • People who received Kadcyla lived significantly longer without their disease getting worse (PFS) compared to those who received lapatinib plus Xeloda (HR=0.65, 35 percent reduction in the risk of disease worsening or death, p<0.0001; median PFS 9.6 months vs. 6.4 months).
  • No new safety signals were observed and adverse events (AEs) were consistent with those seen in previous studies, with fewer people who received Kadcyla experiencing Grade 3 or higher (severe) AEs than those who received lapatinib plus Xeloda (43.1 percent vs. 59.2 percent).
  • For people receiving Kadcyla, the most common (occurring in more than 2 percent of participants) Grade 3 or higher AEs were low platelet count (14.5 percent), increased levels of enzymes released by the liver and other organs (8.0 percent), low red blood cell count (4.1 percent), low levels of potassium in the blood (2.7percent), nerve problems (2.2percent) and tiredness (2.5percent).

 

Source: Roche 

Roche’s obinutuzumab (GA101) delayed disease progression longer than MabThera/Rituxan in people with one of the most common forms of blood cancer

  • Phase III CLL11 study showed GA101 plus chlorambucil, a chemotherapy, was superior to MabThera/Rituxan plus chlorambucil in helping people with previously untreated chronic lymphocytic leukemia live longer without their disease worsening
  • Final data from the CLL11 study will be submitted to the American Society of Hematology’s 55th Annual Meeting in December 2013

Roche  announced positive results from the phase III CLL11 study. At a pre-planned interim analysis, an independent data monitoring committee determined that the study met its primary endpoint showing that GA101 plus chlorambucil helped people live significantly longer without their disease worsening (progression-free survival; PFS) compared to MabThera/Rituxan plus chlorambucil. The CLL11 study is being conducted in cooperation with the German CLL Study Group (GCLLSG). These final data were reached well ahead of the target completion date in 2014 as a result of the magnitude of difference seen between the two study arms. No new safety signals for GA101 or MabThera/Rituxan were identified in this analysis, and adverse events were similar to those observed in the first stage of the study which was previously reported earlier this year.

“The positive final results from the CLL11 study show the promise that GA101 could hold for people with CLL,” said Hal Barron, M.D., Roche’s Chief Medical Officer and Head, Global Product Development. « It is important to explore the potential of this medicine in other types of blood cancer, and our broad development program includes studies in aggressive and indolent lymphoma that compare GA101with MabThera/Rituxan. »

GA101 is the first type II anti-CD20 medicine that is glycoengineered, which means specific sugar molecules in GA101 were modified to change its interaction with the body’s immune cells.

This modification creates a unique antibody that is designed to act as an immunotherapy, engaging the patient’s own immune system to help attack the cancerous cells; in addition, GA101 binds to CD20 with the aim of inducing direct cell death.

These data will be submitted for consideration to the 55th Annual Meeting of the American Society of Hematology (ASH) in New Orleans, which is taking place December 7-10, 2013.

Based on an earlier analysis (stage 1) of the CLL11 study, marketing applications for GA101 were submitted to regulatory authorities including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in April, 2013. Due to the significance of the positive trial results and the serious and life threatening nature of CLL, the FDA granted the GA101 application both Breakthrough Therapy Designation and Priority Review.

 

Source : Roche

Erytech Announces Fast-Off of its Phase IIB Study in Acute Myeloid Leukemia

The study, a multicentre, open, randomized, controlled Phase IIb trial evaluating efficacy and tolerability of GRASPA® in the treatment of newly diagnosed acute myeloid leukemia (AML) patients, over 65 years, unfit for intensive chemotherapy, was initiated in March 2013.

In the mean time and in line with the planning, all 21 French investigation sites have been authorized to participate in the study. With 13 of these sites having been initiated and opened so far, already 12 out of a total of 123 patients have been enrolled in the study. The current pace of inclusion shall enable ERYTECH to recruit the last patient in the study before the end of 2014. In parallel to the patient recruitments realized in France, it is foreseen to open other specialized centers in different European countries in view of internationalizing the study and further accelerating patient enrollment.

The study is performed in collaboration with Orphan Europe (Recordati Group), ERYTECH’s partner for the commercialization of GRASPA® in 38 pays European countries, under a licensing and distribution agreement that was signed at the end of 2012.

In February 2013, the European Medicines Agency (EMA) granted GRASPA® the orphan drug status for the treatment of AML. The orphan drug status provides certain advantages for the sponsor such as reduced procedure costs and ten years of commercial exclusivity.

With about 34 000 new patients per year in Europe and the US, AML is the most common type of acute leukemia. Affecting mainly the adult and senior patient population that often cannot tolerate the existing forms of asparaginase products, AML represents one of the highest mortality rates among all type of cancers and an important unmet medical need.

To address this challenge, ERYTECH can build on its solid experience in Acute Lymphoblastic Leukemia (ALL) where GRASPA®, currently in Phase III of clinical development, has already demonstrated convincing clinical results both in terms of safety and efficacy in fragile adult and senior patients. In ALL, GRASPA® benefits from the orphan drug status both in Europe and in the US.

« We are very pleased with the fast take-off of this study and by the adoption of GRASPA® by the clinicians, confirming their need for new therapies enabling them to treat adult and senior acute leukemia patients efficiently. The increased tolerability profile obtained through the encapsulation of asparaginase in the red blood cells opens perspectives to treat all patients suffering from acute leukemia, even the most fragile ones, not only the children. » comments Yann Godfrin, co-founder and CSO of ERYTECH.

« Much in line with this Phase IIb study in which patient recruitment is happening at a fast pace, we are pursuing the execution of our clinical development plan we announced during our initial public offering in April. The next steps will concern our studies in ALL in Europe and the US, as well as in solid tumors. » concludes Gil Beyen, Chairman and CEO of ERYTECH.

 

Source: Erytech