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Unum Therapeutics Announces Active Investigational New Drug (IND) Application for ACTR087 in Patients with Relapsed/Refractory B-cell Lymphoma

On June 20, 2016 Unum Therapeutics reported that the investigational new drug (IND) application for ACTR087 for the treatment of adult patients with relapsed/refractory CD20-positive B-cell non-Hodgkin lymphoma, is now active (Press release, Unum Therapeutics, JUN 20, 2016, View Source!2016jun20-unum-therapeutics-announces-ac/vrn7q [SID:1234513465]).

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The IND, which the Company had filed in the United States with the Food and Drug Administration, enables Unum to initiate a multi-center, Phase 1 trial to evaluate the use of ACTR087 in combination with rituximab in this patient population. This trial will be the first U.S.-based clinical program for Unum Therapeutics.

"This is an important milestone in our strategy to identify and develop ACTR T-cell immunotherapies to combat a broad range of cancers," said Michael Vasconcelles, MD, Unum’s Chief Medical Officer. "We are eager to explore the potential of ACTR087 to become an important new treatment option for underserved patients with relapsed/refractory B-cell non-Hodgkin lymphoma. We’re excited to be working with experienced clinical investigators at several leading U.S. academic medical centers in this trial."

Site initiation activities are currently underway and the Company anticipates that study enrollment will begin in the second half of 2016. ACTR087, Unum’s most advanced product candidate, combines the Company’s proprietary Antibody-Coupled T-cell Receptor (ACTR), with rituximab, an anti-CD20 antibody. By binding to tumor cells, rituximab effectively targets the tumor for destruction by the genetically modified ACTR087 T-cells.

"ACTR087 is Unum’s first product candidate with an active IND. This marks an important step as we advance our clinical efforts and continue developing a broad pipeline of novel product candidates based on our universal ACTR technology," said Charles Wilson, PhD, Unum’s President and Chief Executive Officer.

This trial will be an open label Phase 1 dose-escalating study using three doses of genetically modified ACTR T-cells in combination with rituximab in patients with relapsed or refractory CD20-positive B-cell non-Hodgkin lymphoma. The primary objective of this trial is to evaluate the safety and tolerability of ACTR087 in patients with relapsed or refractory CD20-positive B-cell lymphoma. Secondary objectives will include the assessment of efficacy of ACTR087 and measurements of durability and persistence of ACTR087 in the blood. The study will be conducted at several clinical sites in the U.S. and is planned to enroll approximately 45 patients.

About Antibody-Coupled T-cell Receptor (ACTR) Technology and ACTR087

Unum’s proprietary ACTR is a chimeric protein that combines components from receptors normally found on two different human immune cell types – natural killer (NK) cells and T-cells – to create a novel cancer cell killing activity. T-cells bearing the ACTR receptor protein can be directed to attack a tumor by combining with a monoclonal antibody that binds antigens on the cancer cell surface.

In contrast to other T-cell therapy approaches for cancer that are limited to a single cancer cell surface target and, therefore, treat a narrow set of tumors, Unum’s approach is not restricted by a specific tumor cell antigen and, thus, may have applications for treating many different types of cancers when combined with the right antibody.

Unum is developing ACTR in combination with a range of tumor-targeting antibodies for use in both hematologic and solid tumor indications. ACTR087, Unum’s most advanced product candidate, combines Unum’s proprietary ACTR, with rituximab, an anti-CD20 antibody. The ACTR087 study will be the first clinical trial using a viral vector to permanently insert the ACTR gene into the genome of patient T-cells.

About B-cell non-Hodgkin Lymphoma

B-cell non-Hodgkin lymphoma, a collection of many distinct forms of cancer arising from specific immune cells called B lymphocytes, is one of the most common cancers in the United States. The American Cancer Society estimates that in 2016 alone, approximately 72,000 people will be diagnosed with this disease.[i] Though B-cell non-Hodgkin lymphoma is treatable with a variety of available cancer medicines, and some forms of the disease may be curable with initial chemotherapy-based treatment, patients whose disease relapses after treatment or is refractory to available therapies face limited treatment options, and historically their outcomes are poor.

Kite Pharma Opens State-of-the-Art T-Cell Therapy Manufacturing Facility

On June 20, 2016 Kite Pharma, Inc. (Nasdaq: KITE), a clinical-stage biopharmaceutical company focused on developing engineered autologous T-cell therapy (eACT) products for the treatment of cancer, reported the official opening of its new commercial manufacturing facility in El Segundo, California (Press release, Kite Pharma, JUN 20, 2016, View Source [SID:1234513463]).

Over 300 employees, investors and company partners attended the unveiling of the 43,500-square-foot, state-of-the-art plant. The facility has been designed to produce chimeric antigen receptor (CAR) and T-cell receptor (TCR) product candidates for clinical trials, as well as for the potential launch and commercialization of Kite’s lead CAR T-cell product candidate, KTE-C19, which is in clinical study for the treatment of chemorefractory diffuse large B-cell lymphoma (DLBCL) and other B-cell malignancies. Kite anticipates commercial launch of KTE-C19 in 2017.

The facility is estimated to have the capacity to produce up to 5,000 patient therapies per year. The plant’s location, adjacent to Los Angeles International Airport, is intended to expedite receipt and shipment of engineered T-cells from and to patients across the United States and Europe.

"Establishing world-class manufacturing capability has always been a priority for Kite," said Timothy Moore, Kite’s Executive Vice President of Technical Operations. "Through our continuous efforts to optimize manufacturing, supply chain and quality control, our proprietary process now reduces the time from when a patient’s materials are shipped to our facility to when the engineered T cells are returned to the patient to approximately 14 days, one of the fastest in the industry."

Underscoring the company’s focus on execution and commitment to the future delivery of immuno-oncology therapies, the El Segundo facility is expected to be operational by the end of this year for clinical production, less than two years after the site groundbreaking in February 2015. The El Segundo facility will complement Kite’s existing clinical manufacturing facilities in Santa Monica, California, that are currently producing therapies for Kite’s ongoing clinical trials.

"We are excited and proud to celebrate the opening of our El Segundo manufacturing facility, the latest milestone in our mission to deliver a potentially transformative therapy to patients with a significant unmet need," said Arie Belldegrun, M.D., FACS, Kite’s Chairman, President and Chief Executive Officer. "If approved by the FDA, this site will become a model factory serving patients all over the country. We will also continue to innovate and introduce next generation manufacturing technologies at our facility."

About Kite’s ZUMA Clinical Programs for KTE-C19

KTE-C19 is an investigational therapy in which a patient’s T-cells are genetically modified to express a CAR that is designed to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias. Kite is currently enrolling four pivotal studies (also known as ZUMA studies) for KTE-C19 in patients with various B-cell malignancies.

Study Phase Indication Status
ZUMA-1 Phase 2 Pivotal
NCT02348216 (N=112) Chemorefractory DLBCL, PMBCL, TFL Phase 2 enrolling
ZUMA-2 Phase 2 Pivotal
NCT02601313 (N=70) Relapsed/refractory MCL Phase 2 enrolling
ZUMA-3 Phase 1/2 Pivotal
NCT02614066 (N=75) Relapsed/refractory Adult ALL Phase 1/2 enrolling
ZUMA-4 Phase 1/2 Pivotal
NCT02625480 (N=75) Relapsed/refractory Pediatric ALL Phase 1/2 enrolling

DLBCL = diffuse large B-cell lymphoma
PMBCL = primary mediastinal B-cell lymphoma
TFL = transformed follicular lymphoma
MCL = mantle cell lymphoma
ALL = acute lymphoblastic leukemia

Kite Pharma Expands Development of T-Cell Receptor (TCR) Therapies Targeting HPV-Associated Cancers in Partnership with the National Cancer Institute (NCI)

On June 20, 2016 Kite Pharma, Inc. (NASDAQ:KITE) reported that it has entered into a new Cooperative Research and Development Agreement (CRADA) with the Experimental Transplantation and Immunology Branch (ETIB) of the National Cancer Institute (NCI) for the research and clinical development of T-cell receptor (TCR) product candidates directed against human papillomavirus (HPV)-16 E6 and E7 oncoproteins for the treatment of HPV-associated cancers (Press release, Kite Pharma, JUN 20, 2016, View Source [SID:1234513461]).

Under the CRADA, NCI will evaluate a novel TCR therapy candidate targeting HPV-16 E7 as a monotherapy and in combination with a checkpoint inhibitor in HPV-16 associated solid tumors. This Phase 1/2 clinical study will be led by Christian S. Hinrichs, M.D., from the ETIB and lead investigator of this CRADA. The NCI will also continue to advance a separately designed TCR therapy candidate targeting HPV-16 E6, currently in a Phase 1/2 clinical trial, under an existing CRADA between Kite and the Surgery Branch of the NCI, led by Steven A. Rosenberg, M.D., Ph.D.

"TCR therapies allow targeting of viral oncoproteins that are not effectively addressed with other existing therapeutic modalities. HPV-16 E6 and E7 TCR therapies hold the potential to address the significant unmet medical need that exists in HPV-associated cancers," said Arie Belldegrun, M.D., FACS, Kite’s Chairman, President, and Chief Executive Officer. "We are excited to collaborate with the network of talented investigators at the NCI as we advance our HPV-associated cancer therapy pipeline."

About HPV-Associated Cancers

Human papillomavirus (HPV) has a causal role in nearly all cervical cancers, and in many head and neck, and anogenital malignancies. HPV-16 is the most commonly found strain in these cancers. More than 33,000 cases of HPV-associated cancers are diagnosed each year in the US, and more than 11,000 annual deaths are attributed to the diseases, according to the Centers for Disease Control and Prevention. Current therapies for advanced HPV-associated tumors have low response rates and poor response duration.

Adaptimmune Receives Positive Opinion for Orphan Drug Designation in the European Union for SPEAR™ T-cell Therapy Targeting NY-ESO for Treatment of Soft Tissue Sarcoma

On June 20, 2016 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported that the European Medicines Agency’s (EMA) Committee for Orphan Medicinal Products (COMP) has adopted a positive opinion recommending the company’s SPEAR T-cell therapy targeting NY-ESO for designation as an orphan medicinal product for the treatment of soft tissue sarcoma, a solid tumor cancer (Press release, Adaptimmune, JUN 20, 2016, View Source [SID:1234513460]).

Adaptimmune previously received orphan drug destination from the U.S. Food and Drug Administration for its NY-ESO SPEAR T-cell therapy in this indication.

"While unresectable or metastatic soft tissue sarcomas are rare, they are associated with a high mortality rate," said Dr. Rafael Amado, Adaptimmune’s Chief Medical Officer. "We are pleased to have received an opinion from the Committee for Orphan Medicinal Products which recognizes the unmet medical need that soft-tissue sarcomas represent. We look forward to working with them to advance our NY-ESO SPEAR T-cell therapeutic candidate through clinical evaluation, with the goal of one day bringing it to patients throughout Europe suffering from this disease."

The COMP adopts an opinion on the granting of orphan drug designation, after which the opinion is submitted to the European Commission for endorsement. Orphan drug designation by the European Commission provides certain regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than five in 10,000 persons in the European Union, and where no satisfactory treatment is available. Orphan drug designation provides incentives for companies seeking protocol assistance and scientific advice from the EMA during the product development phase and a 10-year period of marketing exclusivity in the EU following product approval.

Data from recent published epidemiological studies estimate the prevalence of soft tissue sarcoma in the European Union to be 2.86 per 10,000 which corresponds to approximately 146,918 people based on the total population of 513.7 million people in the EU, Norway, Iceland, and Liechtenstein as of January 1, 2015 [EUROSTAT 2015].

Adaptimmune is developing its NY-ESO SPEAR T-cell therapy in certain soft tissue sarcomas. The company expects to initiate pivotal studies in synovial sarcoma in 4Q16/1Q17, and will explore development in myxoid round cell liposarcoma. Adaptimmune’s SPEAR T-cell candidates are novel cancer immunotherapies that have been engineered to target and destroy cancer cells by strengthening a patient’s natural T-cell response. T-cells are a type of white blood cell that play a central role in a person’s immune response. Adaptimmune’s goal is to harness the power of the T-cell and, through its multiple therapeutic candidate, significantly impact cancer treatment and clinical outcomes of patients with solid and hematologic cancers.

About Soft Tissue Sarcoma
Soft tissue sarcomas can develop from soft tissues including fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues. There are approximately 50 types of soft tissue sarcomas, including synovial sarcoma, a cancer of the connective tissue around the joints. Soft tissue sarcomas can develop at almost any anatomic site, such as the extremities, trunk or thorax, abdomen and retroperitoneum, pelvis and the head and neck region. The more common soft tissue sarcomas originate from muscle, nerve tissue, fat, or deep skin tissue. For a number of sarcomas, such as synovial sarcoma, the tissue origin is not well characterized. Surgical resection is the standard therapy for localized disease and radiation therapy (preoperative or postoperative) and/or chemotherapy is added in selected cases.

Epizyme Reports Early Data from Global Phase 2 Trial of Tazemetostat in Non-Hodgkin Lymphoma at ASH Lymphoma Biology Meeting

On June 19, 2016 Epizyme, Inc. (NASDAQ: EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported preliminary data from its ongoing, global Phase 2 clinical trial of orally administered tazemetostat, a first-in-class EZH2 inhibitor, in relapsed or refractory patients with non-Hodgkin lymphoma (NHL) (Press release, Epizyme, JUN 19, 2016, View Source [SID:1234513457]). Early data from the Phase 2 trial indicate that tazemetostat demonstrated a favorable safety profile and clinical activity consisting of objective responses in a heavily pre-treated patient population. These data were reported at the American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting on Lymphoma Biology.

Epizyme’s Independent Data Monitoring Committee confirmed that futility has been surpassed in four of the five study cohorts: diffuse large B-cell lymphoma (DLBCL) with Germinal Center B-cell (GCB) subtype and EZH2 mutations; DLBCL with GCB subtype and wild-type EZH2; DLBCL with non-GCB subtype; and, follicular lymphoma (FL) with EZH2 mutations. The fifth cohort enrolling patients with FL with wild-type EZH2 is ongoing, but has not yet reached futility assessment. The primary endpoint of the Phase 2 study is overall response rate1, and secondary endpoints include progression-free survival and duration of response.

"Patients with relapsed or refractory NHL are often faced with limited treatment options, particularly those who are highly refractory or whose disease is multiply relapsed as we have seen in this study population," said Franck Morschhauser, M.D., Ph.D., Centre Hospitalier Régional Universitaire de Lille, France, and primary investigator on the Phase 2 study. "These patients are in need of new therapeutic options, and while these data are early, we are encouraged and look forward to further understanding the impact that tazemetostat could have on patients as the trial proceeds."

Trial enrollment is on track and consistent with incidence rates for NHL subtypes, with approximately 20% of enrolled DLBCL GCB and FL patients having EZH2 mutations. As of the data cutoff2, 82 patients across all five study arms were evaluable for safety. Efficacy has been assessed on 47 evaluable patients from the four cohorts confirmed to have surpassed their pre-specified futility hurdles. The non-evaluable patients include 16 patients in the arms that have surpassed futility that are too early for efficacy evaluation or for whom data are not yet entered and 19 patients from the fifth cohort who have FL with wild-type EZH2.

Tazemetostat has demonstrated a favorable safety profile in all patients treated, consistent with the experience observed in the Phase 1 trial. The majority of adverse events were grade 1 or grade 2 within the 82 safety-evaluable patients. The most common treatment-related adverse events (≥5%) were nausea, asthenia, thrombocytopenia, neutropenia and fatigue, of which seven were grade 3 or higher. All adverse events resulted in low rates of both dose reductions (4%) and dose discontinuations (6%).

Among the 47 efficacy-evaluable patients, both objective responses (complete responses (CR) and partial responses (PR)) and stable disease (SD) have been observed. In the Phase 1 experience, Epizyme observed responses that evolved over time from SD to PRs and CRs. At data cutoff, best responses across the four cohorts were as follows:

DLBCL with GCB subtype and EZH2 mutations (n=5): one PR and two SD;
DLBCL with GCB subtype and wild-type EZH2 (n=19): two CRs, one PR and six SD;
DLBCL with non-GCB subtype (n=20): two CRs, four PRs and five SD; and,
FL with EZH2 mutations (n=3): three PRs.
All of the patients who have achieved a CR and the majority of patients who have achieved a PR or SD as best response are still on tazemetostat treatment as of the data cutoff.

"We are pleased by the performance of tazemetostat in the Phase 2 trial so far, which has been consistent with our Phase 1 results," added Peter Ho., M.D., Ph.D., Executive Vice President and Chief Medical Officer, Epizyme. "We have observed patients receiving clinical benefit from tazemetostat and continue to believe that prolonged exposure to treatment has the potential to result in decreased tumor burden over time."

Epizyme is continuing to enroll patients in its ongoing Phase 2 study in patients with NHL, as well as in two clinical trials in patients with certain genetically defined solid tumors.

A slide presentation of the early Phase 2 data of tazemetostat in NHL is available for download on the company’s website.