On May 26, 2015 bluebird bio and Five Prime Therapeutics reported that they have entered into an exclusive license agreement to research, develop and commercialize chimeric antigen receptor (CAR) T cell therapies using Five Prime’s proprietary human antibodies to an undisclosed cancer target for hematologic malignancies and solid tumors (Press release, Five Prime Therapeutics, MAY 26, 2015, View Source [SID:1234504833]). Schedule your 30 min Free 1stOncology Demo! Under the terms of the agreement, Five Prime will provide bluebird bio exclusive rights to its novel human antibodies to the target, and bluebird bio will leverage its proprietary lentiviral gene therapy platform and CAR T capabilities to develop CAR T therapies against the target. Know more, wherever you are: Financial terms of the agreement include a $1.5 million upfront payment and subsequent milestone payments to Five Prime, which together could total over $130 million per licensed product if certain development, regulatory, and commercial milestones are achieved. Five Prime is also eligible to receive tiered royalties on product sales. bluebird bio will conduct and fund clinical development as well as regulatory and commercial activities.
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"CAR T cell therapies have emerged as a very promising approach for treating a number of cancers," said Lewis "Rusty" T. Williams, M.D., Ph.D., chief executive officer & president of Five Prime. "bluebird bio brings a wealth of knowledge in the area of gene therapy, a key component of building CAR T therapeutics. We are also impressed by bluebird bio’s development and manufacturing infrastructure. We feel that bluebird bio is well positioned to succeed with converting Five Prime’s human antibodies to CAR T cell products that can benefit patients, and we are pleased that our proprietary platform continues to demonstrate its versatility in the field of immuno-oncology."
"We are very pleased to enter into this agreement with Five Prime, a company with a track record of success in the characterization and development of therapeutic antibodies to extracellular proteins," said Jeffrey T. Walsh, chief operating officer of bluebird bio. "Five Prime’s program offers a strategic fit to our research and will augment bluebird bio’s growing pipeline of immuno-oncology research and preclinical programs."
Author: [email protected]
Pivotal Study Results Published in Journal of Clinical Oncology Showed Talimogene Laherparepvec Improved Durable Response Rates in Patients With Metastatic Melanoma
On May 26, 2015 Amgen reported the publication of primary results from the Phase 3 OPTiM study in the Journal of Clinical Oncology (JCO) (Press release, Amgen, MAY 26, 2015, View Source [SID:1234504832]). Schedule your 30 min Free 1stOncology Demo! The data published in JCO, which were previously presented at the Annual Meetings of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in 2013 and 2014, demonstrated a significantly higher durable response rate (DRR) in patients with unresected stage IIIB, IIIC or IV metastatic melanoma receiving the investigational oncolytic immunotherapy talimogene laherparepvec compared to those who received granulocyte-macrophage colony-stimulating factor (GM-CSF). Results showed that the primary endpoint of DRR was met, however the secondary endpoint of overall survival (OS) was not met, although there was a strong trend in favor of talimogene laherparepvec.
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"Oncolytic virus immunotherapy may become a new approach to melanoma treatment, and the OPTiM study demonstrated durable responses in talimogene laherparepvec treated patients with metastatic melanoma," said lead investigator Howard L. Kaufman, M.D., associate director for Clinical Science at the Rutgers Cancer Institute of New Jersey and president of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). "Talimogene laherparepvec may offer a potential new treatment option for patients with this aggressive form of skin cancer."
A DRR measures the number of patients who had a complete response or partial response within the first 12 months of treatment and maintained the response continuously for at least 6 months.
The most frequent adverse events (AEs) observed in this study were chills, pyrexia, injection-site pain, nausea, flu-like symptoms and fatigue. The most common serious AEs included disease progression, cellulitis and pyrexia. No treatment-related deaths were observed.
"While there have been some important new treatment options in recent years, the incidence of melanoma has risen dramatically, and we need additional approaches for treating advanced disease," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The OPTiM trial data provide strong evidence supporting the local and distant effects of talimogene laherparepvec and its potential to stimulate a systemic anti-tumor immune response."
The OPTiM data serve as the basis of a Biologics License Application which has been accepted for review by the U.S. Food and Drug Administration (FDA), and a Marketing Authorization Application in the European Union for talimogene laherparepvec for the treatment of adults with regionally or distantly metastatic melanoma. The FDA has set a review goal date under the Prescription Drug User Fee Act of Oct. 27, 2015.
Trial Design
The OPTiM study was a global, randomized, open-label, Phase 3 trial designed to evaluate the safety and efficacy of talimogene laherparepvec compared to a control therapy with GM-CSF in over 400 patients with unresected stage IIIB, IIIC or IV melanoma.
Patients were randomized 2:1 to receive either talimogene laherparepvec intralesionally every two weeks or GM-CSF subcutaneously for the first 14 days of each 28 day cycle. Treatment could last for up to 18 months. Where appropriate, stable or responding patients could receive additional treatment on an extension protocol.
About Talimogene Laherparepvec
Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells that have metastasized. Talimogene laherparepvec was designed to work in two important and complementary ways. First, it is injected directly into tumors where it replicates inside the tumor’s cells causing the cell to rupture and die in a process called lysis. Then, the rupture of the cancer cells can release tumor-derived antigens, along with GM-CSF, that can stimulate a system-wide immune response where white blood cells are able to seek out and target cancer that has spread throughout the body.
Amgen has initiated a comprehensive clinical development program for talimogene laherparepvec in metastatic melanoma, which includes combination studies with checkpoint inhibitors in patients with late-stage disease and monotherapy prior to surgery (neoadjuvant) in patients with resectable disease. Additionally, based on its clinical profile, talimogene laherparepvec has the potential to be studied in a variety of solid tumor types.
About Melanoma
Melanoma is a type of skin cancer that is characterized by the uncontrolled growth of melanocytes, which are the cells responsible for providing the pigment to skin.1 Melanoma is the most aggressive and serious form of skin cancer. Currently, 132,000 melanoma cases occur globally each year.2 In the U.S., while melanoma accounts for less than five percent of skin cancer cases, it causes the most skin cancer deaths.3 The number of new cases of melanoma in the U.S. has been increasing for the last 30 years.3
Melanoma is considered to be advanced when it has spread, or metastasized, from the origin site to deeper parts of the skin or other organs such as the lymph nodes, lungs or other parts of the body distant from the primary tumor site.4
Sophiris Bio Enrolls First Patients in Phase 2a Proof of Concept Prostate Cancer Study
On May 26, 2015 Sophiris Bio reported that the first patients have been dosed in a Phase 2a proof of concept trial of PRX302 as a treatment for localized low to intermediate risk prostate cancer (Press release, Sophiris Bio, MAY 26, 2015, View Source [SID:1234504830]). Schedule your 30 min Free 1stOncology Demo! "The highly targeted treatment with PRX302, which selectively destroys prostate tissue, makes PRX302 a promising treatment approach for localized prostate cancer," stated Professor Mark Emberton, Director of the Division of Surgery and Urologist at University College London. Know more, wherever you are: "This new trial is very exciting. PRX302 has the potential to provide patients with clinically significant, localized low to intermediate risk prostate cancer a tissue-sparing cancer treatment that carries little in the way of side effects," said Dr. Hashim Ahmed, Principal Investigator for the study, Division of Surgery and Interventional Sciences, University College London.
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The Phase 2a proof of concept study is a single-center, open-label study that will enroll approximately 20 patients. Previously obtained multi-parametric magnetic resonance imaging (mpMRI) of tumor lesions in each patient’s prostate, mapped to real-time three-dimensional transrectal ultrasound (TRUS), will be used in the study to guide the injection of PRX302 to treat a single, histological-proven, clinically significant lesion area in each patient’s prostate. Although the primary objective of the study is safety and tolerability, the key efficacy variable is the change in the treated clinically significant lesion on biopsy after six months.
"PRX302 is a novel targeted approach for the treatment of clinically significant, localized prostate cancer that is still confined within the prostate gland," said Allison Hulme, Ph.D., chief operating officer and head of R&D at Sophiris. "PRX302 has been engineered to be activated only by enzymatically active prostate specific antigen (PSA) which is present only in prostate tissue, including the transition zone of the prostate as well as prostate cancer cells. PRX302 can be focally delivered by an intraprostatic injection directly into and around the tumors within the prostate where there are high levels of enzymatically active PSA to activate the drug."
PRX302 for the Targeted Treatment of Localized Prostate Cancer
PRX302 has the potential to provide a focal targeted therapy for the ablation of localized prostate cancer while potentially avoiding many of the complications and side effects associated with whole gland radical treatments. The increasing use of multi-parametric magnetic resonance imaging (mpMRI) and advances in mapping previously obtained mpMRI images with live 3D ultrasound images enable the physician to more accurately locate tumors within the prostate when taking biopsies. This increases the accuracy with which men with clinically significant lesions are identified. It also enables the injection of PRX302 directly into previously identified clinically significant tumors located within the prostate. The targeted focal treatment of prostate cancer is in line with current treatments for solid tumors, such as breast or liver, where the goal is to remove the tumor and preserve as much of the organ as possible.
About Localized Prostate Cancer
Prostate cancer is the second most common form of cancer in men in the US with an estimated 220,800 new cases in 2015. Approximately 80% of patients in the US are diagnosed with localized disease. Research has shown that patients with early localized disease have a low likelihood of the cancer spreading beyond the confines of the prostate; however, men with clinically significant, localized disease choose to undergo radical therapies. Radical therapies include surgery to remove the entire prostate and/or radiation. Potential toxicities from radical treatments can be significant and permanent and include erectile dysfunction, incontinence and rectal toxicity.
Infinity Reports Preclinical Data for Duvelisib Demonstrating Synergy with Standard-of-Care Therapies and Emerging Agents in Development for the Treatment of Hematologic Malignancies
On May 26, 2015 Infinity Pharmaceuticals reported new preclinical data for duvelisib (IPI-145), an investigational, oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma (Press release, Infinity Pharmaceuticals, MAY 26, 2015, View Source [SID:1234504829]). Schedule your 30 min Free 1stOncology Demo! In vitro studies demonstrated synergy with standard-of-care therapies and emerging agents in development for hematologic malignancies, including duvelisib in combination with venetoclax, in combination with ibrutinib and in combination with dexamethasone. Additionally, in preclinical studies with each of these three combinations, significant inhibition of lymphoma tumor growth was observed compared to each of these agents alone. These data will be presented at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, Ill. on Sunday, May 31, 2015.
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"Targeted combinations have the potential to further improve treatment options for patients, and Infinity’s translational research team continues to collaborate with AbbVie, our global partner for duvelisib in oncology, to identify therapies that may be synergistic with duvelisib," stated Vito Palombella, Infinity’s chief scientific officer. "This research supports further development of duvelisib in combination with approved and investigational medicines, including venetoclax."
"Additionally, preclinical research evaluating the activity of PI3K-delta isoform selective inhibitors and PI3K-gamma isoform selective inhibitors together shows that inhibiting both isoforms leads to greater tumor growth inhibition than either isoform alone, suggesting dual inhibition of PI3K-delta and PI3K-gamma has complementary effects on malignant B-cell growth and survival in these preclinical models," Dr. Palombella continued.
Preclinical and Translational Combination Data for Duvelisib (Abstract #8559)
New preclinical and translational research conducted in collaboration with researchers at AbbVie will be reported at ASCO (Free ASCO Whitepaper) 2015 on Sunday, May 31, from 8:00 a.m. – 11:30 a.m. CDT (9:00 a.m. – 12:30 p.m. EDT) in a poster presentation, "High throughput in vitro combination sensitivity screen in hematologic malignancies with the phosphoinositide-3-kinase (PI3K)-delta,gamma inhibitor, duvelisib."
As part of Infinity and AbbVie’s ongoing joint efforts to identify compounds synergistic with duvelisib, researchers conducted an in vitro high-throughput combination screen using a panel of cell lines and various drug combinations. In vitro synergy was observed with standard-of-care therapies and emerging agents in development for hematologic malignancies, including duvelisib in combination with venetoclax, in combination with ibrutinib and in combination with dexamethasone.
Additionally, in preclinical human xenograft studies with each of these three combinations, significant inhibition of lymphoma tumor growth was observed compared to each of these agents alone. These data support the use of duvelisib as part of combination therapy and provide additional rationale for the first clinical study of duvelisib in combination with venetoclax.
Researchers also evaluated the impact of dual inhibition of PI3K-delta and PI3K-gamma using isoform-selective inhibitors in preclinical models. Combined inhibition of PI3K-delta and PI3K-gamma led to greater tumor growth inhibition compared to the inhibition of either PI3K isoform alone, suggesting that dual inhibition of PI3K-delta and PI3K-gamma with duvelisib has complementary effects on malignant B-cell growth and survival in these preclinical models.
Additional Duvelisib Presentations at ASCO (Free ASCO Whitepaper) 2015
In total, four duvelisib presentations will take place on Sunday, May 31, 2015, during a poster session from 8:00 a.m. to 11:30 a.m. CDT in South Hall A at McCormick Place. In addition to the preclinical data reported today, duvelisib presentations at ASCO (Free ASCO Whitepaper) 2015 will include the following:
Phase 1 data describing the clinical activity and pharmacodynamics effects of duvelisib in a cohort of treatment-naïve patients with chronic lymphocytic leukemia (CLL) (Abstract #7074)
Translational data providing insight into the mechanism by which duvelisib disrupts communication between tumor cells and the supporting microenvironment in CLL (Abstract #7072)
A "trials in progress" poster highlighting SYNCHRONY, a Phase 1b study of duvelisib and obinutuzumab in CLL patients whose disease is refractory to or has relapsed while receiving a BTK inhibitor (Abstract #TPS7100)
About Duvelisib
Duvelisib is a dual, oral inhibitor of phosophoinositide-3-kinase (PI3K)-delta and PI3K-gamma that is being jointly developed by Infinity Pharmaceuticals, Inc. and AbbVie Inc. The PI3K pathway is known to play a critical role in regulating the growth and survival of certain types of blood cancers. Duvelisib is designed to block the growth and survival of tumor cells by inhibiting PI3K-delta and PI3K-gamma signaling. The investigational agent is being evaluated in registration-focused studies, including DYNAMOTM, a Phase 2 study in patients with refractory indolent non-Hodgkin lymphoma, DYNAMO+R, a Phase 3 study in patients with previously treated follicular lymphoma, and DUOTM, a Phase 3 study in patients with relapsed/refractory chronic lymphocytic leukemia. Duvelisib is an investigational compound and its safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.
Regeneus receives approval for personalised cancer immunotherapy trial
On May 25, 2015 Regeneus (ASX: RGS), a clinical stage regenerative medicine company, reported that it has received ethics approval to commence its first-in-human trial for a personalised therapeutic cancer vaccine that is aimed at harnessing the body’s own immune system to fight cancer cells (Press release, Regeneus, MAY 25, 2015, View Source [SID1234519521]). Schedule your 30 min Free 1stOncology Demo! The vaccine, known as RGSH4K, is produced from a patient’s own cancer cells and, combined with a proprietary immunostimulant, is designed to activate the immune system against the cancer cells to initiate a body-wide response. The immune system’s memory should recognise and respond to both existing and new tumours.
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The trial has its genesis in promising results in canines. In canine trials, Regeneus worked with the Bill Walsh Translational Cancer Research Laboratory at Royal North Shore Hospital. The vaccines, created using a dog’s own tumour, resulted in the majority of treated dogs outliving the average expected survival time for their particular type of cancer.
"We are hopeful that the success we have seen with the vaccine in treating a wide variety of cancers in dogs translates to humans" said Regeneus CEO, John Martin.
Cancer immunotherapies represent a treatment option without many of the side effects of standard chemotherapy. Cancer vaccines interfere minimally with most chemotherapeutic drugs making them likely helping agents to traditional therapies. The RGSH4K vaccine is simple to manufacture and contains no live cancer cells.
The study known as the ACTIVATE trial, is a single centre, open label, first in-human, Phase 1 dose escalating study to evaluate the safety, tolerability and preliminary efficacy of RGSH4K, administered in 21 patients with advanced cancers.
To facilitate the trial, Regeneus has established an ethics-approved tumour bank. Participants in the trial will need to have stored a tumour sample which then may be used to produce an autologous cancer vaccine for individual patient’s use in the trial. Further detail in relation to the trial and the tumour bank can be found on the Australian New Zealand Clinical Trials Registry website
The Principal Investigators for the trial are leading medical oncologists, Professor Stephen Clarke and Associate Professor Nick Pavlakis from University of Sydney‘s Northern Clinical School at the Kolling Institute of Medical Research located at Royal North Shore Hospital in St Leonards, Sydney. The trial will be conducted through the Northern Cancer Institute in St Leonards.
The cancer vaccine technology was developed at the Bill Walsh Translational Cancer Research Laboratory which is part of the Kolling Institute of Medical Research and is the research arm of the Medical Oncology Department, Royal North Shore Hospital. "It’s exciting to see world-class innovative cancer research done at the Kolling Institute translated into clinical application as a potential new therapeutic cancer vaccine," Professor Clarke said.
Regeneus has the exclusive worldwide rights to develop and commercialise the vaccine technology for human and veterinary applications.
Additional information on the human trials
In this trial, adult patients with a variety of advanced cancer types will be treated using this revolutionary technology. The process will work as follows:
Suitable patients will have their tumour removed and stored (known as tumour banking) prior to commencing first-line treatment;
If the patient relapses, and there are no other useful treatment options available, they will move into the next stage of the trial and, using their excised tumour, have a personalised vaccine produced;
The personalised, or autologous vaccine, will be injected at staged intervals and patients monitored for a response.
Professor Clarke says the aim will be for the cancer to be stabilised and the tumour to shrink. Ideally this would then lead to an extended life expectancy for the patient, similar to the results obtained in the canine research.