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Cell and Gene Therapy Catapult, UCLB and Imperial Innovations announce positive interim review in ongoing AML WT1 T cell clinical trial

On April 12, 2016 The Cell and Gene Therapy Catapult, the UK organisation dedicated to the growth of the UK cell and gene therapy industry by bridging the gap between scientific research and commercialisation, alongside UCL Business PLC (UCLB) and Imperial Innovations, reported a positive interim review in the phase I/II trial conducted by Catapult Therapy TCR using a T cell therapy to target acute myeloid leukaemia (AML) (Press release, UCLB, APR 12, 2016, View Source [SID:1234510708]).

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The review has been conducted by the Data Safety Monitoring Board (DSMB), an independent panel of specialists in the field. The reviewed data shows that in the first cohort comprising 3 patients treated, there was a good safety profile with no serious adverse events (SAEs) related to the WT1-TCR T cell therapy. Importantly, the therapy also met the protocol specified requirements for cell persistence, showing that the WT1 targeted T cells can survive and expand in patients.

Passing this first interim review has enabled the clinical trial to enter its second phase. Dosing has now successfully started in the second cohort of patients in the trial which allows patients to receive a higher dose of the gene modified WT1 TCR T cells.

The therapy uses TCR gene-modified T cells to target WT1-overexpressing cells. It involves modification by gene therapy of the patient’s own T cells, so that they may recognise and destroy WT1-expressing cells when infused back into the body. It shows potential in disorders such as acute myeloid leukaemia and myelodysplastic syndrome and has been ranked by the US National Cancer Institute (NCI) as the number 1 target for cancer immunotherapy.

The trial is operated by Catapult Therapy TCR Limited, a company formed by the Cell and Gene Therapy Catapult with UCLB and Imperial Innovations to develop the T cell therapy, and is supported by the NIHR Biomedical Research Centre (BRC) at University College London Hospitals. Pre-clinical development of the TCR gene therapy programme was supported by Bloodwise, previously Leukaemia and Lymphoma Research. In August 2015 the Cell and Gene Therapy Catapult appointed Cellular Therapeutics Limited (CTL), as a manufacturer for the clinical trial.

"Developing TCR gene-modified T cells to target WT1-overexpressing cells continues to show promise as an immunotherapy for a range of cancers including the trials that we have underway in acute myeloid leukaemia and myelodysplastic syndrome," said Keith Thompson, CEO, the Cell and Gene Therapy Catapult. "The progress of the WT1 TCR clinical trials supported by the positive DSMB review, is encouraging and we look forward to expanding these trials across the UK and Europe. Further results are expected during 2017."

"We are delighted with the progress of this clinical trial in acute myeloid leukaemia," said Professor Emma Morris, UCL Institute of Immunity and Transplantation, Chief Investigator and co-inventor as well as Director of the Infection, Immunity and Inflammation Programme at the National Institute for Health Research University College London Hospitals Biomedical Research Centre. "This is an important area of unmet medical need and we are progressing with the next stages of recruitment now ongoing in the second cohort of the AML trial."

"We are pleased to note the progress of this innovative therapy," said Tony Hickson, Managing Director of Technology Transfer at Imperial Innovations. "Catapult Therapy TCR is a great example of collaboration between UK universities and technology transfer organisations and we look forward to the results of forthcoming trials."

About the Cell and Gene Therapy Catapult
The Cell and Gene Therapy Catapult was established in 2012 as an independent centre of excellence to advance the growth of the UK cell and gene therapy industry, by bridging the gap between scientific research and full-scale commercialisation. With more than 100 employees focusing on cell and gene therapy technologies, we work with our partners in academia and industry to ensure these life-changing therapies can be developed for use in health services throughout the world. We offer leading-edge capability, technology and innovation to enable companies to take products into clinical trials and provide clinical, process development, manufacturing, regulatory, health economics and market access expertise. We aim to make the UK the most compelling and logical choice for UK and international partners to develop and commercialise these advanced therapies. Regenerative medicine is one of the UK government’s "eight great technologies" that support UK science strengths and business capabilities. The Cell and Gene Therapy Catapult works with Innovate UK. For more information go to ct.catapult.org.uk or visit www.gov.uk/innovate-uk.

Roche announces FDA grants Venclexta(venetoclax) accelerated approval for people with hard-to-treat type of chronic lymphocytic leukemia

On April 12, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) granted accelerated approval to Venclexta (venetoclax) for the treatment of people with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy (Press release, Hoffmann-La Roche , APR 12, 2016, View Source [SID:1234510678]).

The pivotal study showed a clinically meaningful improvement (overall response rate, ORR) in 80.2 percent of people (95 percent CI 71.3-87.3). Venclexta is the first approved medicine designed to help restore a process in which cells self-destruct (apoptosis) by selectively blocking the BCL-2 protein and is Roche’s tenth new medicine approved in the past seven years. Venclexta is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States and commercialised by AbbVie outside of the United States.

"Up to half of people whose CLL progressed have 17p deletion, a genetic marker that makes the disease difficult-to-treat," said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. "Venclexta is the first approved medicine designed to trigger a natural process that helps cells self-destruct, and is a new way to help people who have been previously treated and have this high-risk form of the disease."

Possible serious side effects with Venclexta include pneumonia, low white blood cell count with fever, fever, abnormal immune response that results in low red blood cell count, low red blood cell count and tumor lysis syndrome (TLS). The most common side effects of Venclexta include low white blood cell count, diarrhea, nausea, low red blood cell count, upper respiratory tract infection, low platelet count and tiredness.

The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition based on early evidence suggesting clinical benefit. This indication is approved under accelerated approval based on ORR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Venclexta will be available to people in the United States within approximately one week. For those who qualify, Genentech and AbbVie plan to offer patient assistance programs for people taking Venclexta.

Venclexta was granted Breakthrough Therapy Designation by the FDA for the treatment of people with previously treated (relapsed or refractory) CLL with 17p deletion. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. The New Drug Application for Venclexta was granted Priority Review, a designation for medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.

A Marketing Authorization Application (MAA) has also been validated by the European Medicines Agency (EMA).

About the M13-982 Study

M13-982 (NCT01889186) is a Phase II, open-label, single arm, multicenter study evaluating the safety and efficacy of Venclexta (400 mg orally once daily following a weekly ramp-up schedule for the first five weeks) in patients with relapsed, refractory or previously untreated chronic lymphocytic leukemia (CLL) with 17p deletion. The study included 106 patients with relapsed or refractory disease with 17p deletion. In the study, 17p deletion was confirmed in blood samples from patients using the Vysis CLL FISH Probe Kit, which is FDA-approved for selection of patients for Venclexta treatment. The primary endpoint of the study is overall response rate (ORR) as determined by an independent review committee (IRC), and secondary endpoints include complete response (CR), partial response (PR) and duration of response (DOR). The level of minimal residual disease (MRD) in peripheral blood and bone marrow was assessed in a subset of patients. Results showed:

The study met its primary endpoint, with an ORR of 80.2 percent with Venclexta,

as assessed by IRC (95 percent CI 71.3-87.3).

In addition, 7.5 percent of patients achieved a complete response with complete or incomplete recovery of blood counts in the bone marrow (5.7 percent CR, 1.9 percent CRi, respectively).

Median DOR has not been reached with approximately 12 months median follow-up (DOR range: 2.9 to more than 19.0 months).
MRD was evaluated in the blood and bone marrow for those who achieved a CR or CRi following treatment with Venclexta. Three percent (3/106) were MRD-negative, meaning no cancer could be detected using a specific test.

A pooled safety analysis of 240 patients with previously treated CLL from three clinical trials showed serious side effects were reported in 43.8 percent of patients. The most frequent serious side effects (occurring in at least 2 percent of patients) were pneumonia, low white blood cell count with fever, fever, abnormal immune response that results in low red blood cell count, low red blood cell count and tumor lysis syndrome (TLS). The most common Grade 3 or 4 side effects were low white blood cell count (41 percent), low red blood cell count (18 percent) and low platelet count (15 percent).

About Chronic Lymphocytic Leukemia (CLL)

CLL is the most common type of adult leukemia, and in 2016, there will be an estimated 4,660 deaths from the disease in the United States. Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of cancerous cells.

In certain cases of CLL, a part of chromosome 17 is lost and along with it an important gene that controls apoptosis (programmed cell death) called p53. The 17p deletion is found in 3 to 10 percent of previously untreated cases and up to 30 to 50 percent of relapsed or refractory cases.

About Venclexta
Venclexta is a small molecule designed to selectively bind and inhibit the BCL-2 protein, which plays an important role in a process called apoptosis (programmed cell death). Overexpression of the BCL-2 protein in chronic lymphocytic leukemia (CLL) has been associated with resistance to certain therapies. It is believed that blocking BCL-2 may restore the signaling system that tells cells, including cancer cells, to self-destruct. Venclexta is being developed by AbbVie and Roche. Together, the companies are committed to research with Venclexta, which is currently being evaluated in Phase III clinical trials for the treatment of relapsed, refractory and previously untreated CLL, along with studies in several other cancers. Venclexta is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States and commercialised by AbbVie outside of the United States.

About Roche in haematology
For more than 20 years, Roche has been developing medicines that redefine treatment in haematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. In addition to approved medicines MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab) and in collaboration with AbbVie, Venclexta (venetoclax), Roche’s pipeline of investigational haematology medicines includes an anti-PDL1 antibody (atezolizumab/MPDL3280A), an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and a small molecule antagonist of MDM2 (idasanutlin/RG7388). Roche’s dedication to developing novel molecules in haematology expands beyond oncology, with the development of the investigational haemophilia A treatment emicizumab (ACE910).

MSD and Taiho Enter into Co-Promotion Agreement in Japan for Pembrolizumab, MSD’s Immune Checkpoint Inhibitor (Anti-PD-1 Therapy)

On April 11 , 2016 – MSD K.K. also known as Merck in the US and Canada (MSD; President and Representative Director : Tony Alvarez) and Taiho Pharmaceutical C o ., L td . ( Taiho ; President and Representative Director : Masayuki Kobayashi) reported that they have entered into a co – promotion agreement in Japan for pembrolizumab (generic name; development code: MK – 3475) , an immune checkpoint inhibitor (anti – PD – 1 therapy) of which MSD has filed an application for approval in Japan (Press release, Taiho, APR 11, 2016, View Source [SID:1234512291]).

Under the agreement, T aiho will co-promote pembrolizumab with MSD while MSD will manufacture and distribute it.

Pembrolizumab , an immune checkpoint inhibitor (anti – PD – 1 therapy), is a humanized monoclonal antibody that blocks the interaction between PD – 1 mainly expressed on activated lymphocytes with anti – tumor activity, and its ligands, PD – L1 and PD – L2 expressed mainly on tumor cells. By binding to the PD – 1 receptor and blocking the interaction with the receptor ligands, pembrolizumab releases the PD – 1 pathway – mediated inhibition of the immune response, including the anti – tumor immune response.

In Japan, an application for marketing approval was submitted for the anti – PD – 1 antibody pembrolizumab (genetic recombination), for the treatment of patients with unresectable or metastatic melanoma on December 22, 2015, and for the treatment of patients with unresectable advanced or recurrent non – small cell lung cancer on February 29, 2016.

The ongoing clinical program s are for bladder cancer, lung cancer, breast cancer, gastric cancer, head and neck cancer, multiple myeloma, esophageal cancer, colorectal cancer, Hodgkin’s lymphoma, and a dvanced solid tumor. Pembrolizumab is one of the first medicines included in the Ministry of Health, Labor and Welfare’s Sakigake Fast – Track Review, for the treatment of unresectable advanced or recurrent gastric cancer on October 27, 2015. MSD and Taiho will further contribute to patients and healthcare providers in the oncology area by establishing a close partnership with co-promotion of pembrolizumab, a promising new option for cancer treatment

Five Prime Therapeutics Announces FPA144 Will Be Featured During a Special Session at the 2016 AACR Annual Meeting

On April 11, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that it will present the FPA144 program during a special session at the 2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held April 16-20 in New Orleans (Press release, Five Prime Therapeutics, APR 11, 2016, View Source [SID:1234510920]).

The presentation, titled "FPA144: A Therapeutic Monoclonal Antibody with Enhanced Antibody Dependent Cell Killing for the Treatment of Fibroblast Growth Factor Receptor 2b Overexpressing Cancers," will take place during the session titled "New Drugs on the Horizon" on Sunday, April 17, at 5:51 PM (CDT). The presentation will be made available on the publications page of the Five Prime website following the presentation.

About FPA144

FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy for tumors that over-express FGFR2b, as determined by a proprietary immunohistochemistry (IHC) diagnostic assay. FPA144 is designed to block tumor growth through two distinct mechanisms. First, it binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. Second, it has been engineered to drive immune-based killing of tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC) and the recruitment of natural killer (NK) cells. FGFR2 gene amplification (as identified by FISH) is found in a number of tumors, including in approximately 5% of gastric cancer patients, and is associated with poor prognosis.

FDA grants priority review for Roche’s cancer immunotherapy atezolizumab in specific type of lung cancer

On April 11, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) and granted Priority Review for atezolizumab (anti-PDL1; MPDL3280A) for the treatment of people with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease expresses the protein PD-L1 (programmed death ligand-1), as determined by an FDA-approved test, and who have progressed on or after platinum-containing chemotherapy (Press release, Roche Molecular Diagnostics, APR 11, 2016, View Source [SID:1234510663]).

"In a study of atezolizumab in people with previously treated advanced lung cancer, PD-L1 expression correlated with how well they responded to the medicine," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "The goal of PD-L1 as a biomarker is to identify people most likely to benefit from atezolizumab alone."

Atezolizumab was granted Breakthrough Therapy Designation by the FDA in February 2015 for the treatment of people whose NSCLC expresses PD-L1 and whose disease progressed during or after standard treatments (e.g., platinum-based chemotherapy and appropriate targeted therapy for EGFR mutation-positive or ALK-positive disease). Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure that people have access to them through FDA approval as soon as possible. The BLA submission for atezolizumab is based on results from clinical trials including the Phase II BIRCH study, and the FDA will make a decision on approval by Oct. 19, 2016. A Premarket Application (PMA) is also under review by the FDA for a companion immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics.
This is the second BLA acceptance and priority review for atezolizumab. On 15th March, Roche announced that the FDA had accepted the company’s BLA and granted Priority Review for atezolizumab for the treatment of people with locally advanced or metastatic urothelial carcinoma (mUC) who had disease progression during or following platinum-based chemotherapy in the metastatic setting, or whose disease worsened within 12 months of receiving platinum-based chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). Atezolizumab is also being studied in a number of other cancers.

About the BIRCH study
BIRCH is an open-label, multicenter, single-arm Phase II study that evaluated the safety and efficacy of atezolizumab in 667 people with locally advanced or metastatic NSCLC whose disease expressed PD-L1. PD-L1 expression was assessed for both tumor cells and tumor-infiltrating immune cells with an investigational IHC test based on the SP142 antibody. People in the study received a 1200-mg intravenous dose of atezolizumab every three weeks. The primary endpoint of the study was objective response rate (ORR) as assessed by an independent review facility (IRF) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included duration of response (DOR), overall survival, progression-free survival and safety.

About non-small cell lung cancer
Lung cancer is the leading cause of cancer death globally. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day. Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.

About atezolizumab
Atezolizumab (also known as MPDL3280A; anti-PDL1) is an investigational monoclonal antibody designed to bind with a protein called programmed death ligand-1 (PD-L1). Atezolizumab is designed to directly bind to PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells. Atezolizumab may also affect normal cells.

About personalised cancer immunotherapy
The aim of personalised cancer immunotherapy (PCI) is to provide individual patients with treatment options that are tailored to their specific needs. Our PCI research and development programme comprises more than 20 investigational candidates, eight of which are in clinical trials. All studies include the prospective evaluation of biomarkers to determine which people may be appropriate candidates for our medicines. In the case of atezolizumab, PCI begins with the PD-L1 (programmed death ligand-1) IHC assay based on the SP142 antibody developed by Roche Tissue Diagnostics. The goal of PD-L1 as a biomarker is to identify those people most likely to experience clinical benefit with atezolizumab as a single agent versus those who may benefit more from combination approaches; the purpose is to inform treatment strategies which will give the greatest number of patients a chance for transformative benefit.The ability to combine atezolizumab with multiple chemotherapies may provide new treatment options to people across a broad range of tumours regardless of their level of PD-L1 expression.

Personalised Cancer Immunotherapy is an essential component of how Roche deliver on the broader commitment to personalised healthcare. For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.