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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]).

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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.

Cell Medica and Baylor College of Medicine announce exclusive licensing agreement and co-development partnership to create next generation cellular immunotherapy products for the treatment of cancer

On July 17, 2016 Cell Medica, a leader in developing, marketing and manufacturing cellular therapeutics for cancer and infections, reported a ground-breaking co-development partnership with Baylor College of Medicine (Baylor) to develop next-generation technologies for engineering immune cells with enhanced functions for the treatment of solid tumors (Press release, Cell Medica, JUN 17, 2016, View Source [SID1234527733]). The collaboration provides Cell Medica with an exclusive license over several Baylor cell and gene technologies and an option to license new products introduced into the co-development partnership by Baylor’s leading research teams in the field of genetically engineered immune cells.

Next generation technology

The collaboration will build on the recent clinical success of advanced chimeric antigen receptors (CARs) to enable human immune cells to recognize and kill cancer cells expressing tumor-associated antigens. The development plan will apply the CAR technology to natural killer T (NKT) cells as a novel immune cell type with biological properties that may be particularly effective for targeting solid tumors. NKT cells are known to infiltrate tissues where solid tumors arise and kill both malignant cells and cancer-enabling cells such as tumor-associated macrophages. The development plan also includes a genetically engineered T cell receptor (TCR) for use in NKT cells and T cells. The next-generation product concepts will combine the targeting aspects of CAR and TCR technologies with functional engineering to enable the modified immune cells to counteract the powerful inhibitory mechanisms that tumor cells deploy to evade the immune response. Cell Medica expects the collaboration to generate a significant number of new products for its cellular immunotherapy pipeline.

Co-development structure

The collaboration will accelerate the pioneering work of Dr. Leonid Metelitsa, Professor of Paediatrics – Oncology, with CAR-modified NKT cells. In published research, Metelitsa and his team have shown the potential therapeutic advantages of functionally enhanced CAR-modified NKT cells in pre-clinical cancer models. Metelitsa’s research team is part of Texas Children’s Cancer Center and the Center for Cell and Gene Therapy (CAGT) at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist Hospital. The CAGT has more than 20 years of experience working with genetically modified immune cells for the treatment of cancer and has conducted more than 40 clinical studies investigating cellular immunotherapies for the treatment of cancer.

Within the co-development structure, Baylor will conduct the pre-clinical and Phase I clinical research under the guidance of the Joint Steering Committee including members from both organizations. Cell Medica will work in parallel to support early product development and will use its substantial experience in manufacturing clinical-grade cell therapies since 2008 to establish robust production processes suitable for industrial scale-up. Following completion of successful Phase I studies, the products will transfer to Cell Medica for later-stage clinical development and commercialization.

The co-development funding will be available to research teams at Baylor with respect to new technologies, which may be utilized to create therapeutic products using modified NKT cells and other immune cells or to improve manufacturing systems. Baylor’s Innovation Development Center (IDC), led by Andrew Wooten, helped to structure this unique co-development partnership and will be responsible for Baylor’s alliance management function. As part of these responsibilities, the IDC will identify complementary technologies from ongoing Baylor research programs that may be included within the co-development plan.

Five product programs have been defined for the initial development plan in addition to a general process technology program. The preclinical development work for two of these programs will be executed by Drs. Gianpietro Dotti and Barbara Savoldo at the Lineberger Comprehensive Cancer Center, University of North Carolina. The Joint Steering Committee for the collaboration will review new product opportunities on a regular basis.

The co-development partnership builds upon the ongoing successful collaboration between Baylor and Cell Medica, supported by the Cancer Prevention and Research Institute of Texas (CPRIT), to develop baltaleucel-T for the treatment of a range of cancers associated with the oncogenic Epstein Barr virus.

License, Option and Co-development Arrangements

Cell Medica has entered into a License and Option Agreement for two platform patents related to engineered NKT cells, three target cancer antigens for CAR-modified NKT cells and a T cell receptor (TCR) technology. In addition, Baylor and Cell Medica have signed a co-development agreement under which Cell Medica will fund research aimed at new products as well as concepts/technologies in both oncology and non-oncology applications. Cell Medica will have an exclusive option to license future products within the co-development plan. Cell Medica has paid an up-front fee for the exclusive licensing arrangements and will make additional payments to exercise its exclusive option to license future products. Baylor is eligible to receive further payments related to late-stage clinical, regulatory approval and sales milestones, as well as single digit royalties for the successful development of specific products. As part of the up-front consideration, Baylor will receive Cell Medica Preference Shares, which are convertible into Common Shares. Specific financial terms have not been disclosed.

"We are very pleased to partner with Cell Medica in a collaboration aimed at unlocking the huge potential of cellular immunotherapy for the benefit of cancer patients," said Dr. Adam Kuspa, senior vice president and dean for research at Baylor College of Medicine. "The co-development partnership represents a novel aspect of this collaboration which will fully engage Baylor in the early stage development work, including Phase I studies".

"This collaboration with Baylor College of Medicine will place Cell Medica at the forefront of new product concepts for CAR-modified immune cells," noted Gregg Sando, CEO of Cell Medica. "Baylor’s leading research capability in this field should add significantly to our pipeline of high value products targeting cancer types that do not respond to conventional treatments."

8-K – Current report

On June 15, 2016 Cellectar Biosciences, Inc. (Nasdaq:CLRB) ("the company"), an oncology-focused biotechnology company, reported the results of a preliminary tumor-targeting study that shows its prototype paclitaxel chemotherapeutic conjugate, CLR 1602, may be up to 30 times more tumor selective in comparison to free paclitaxel (Filing, 8-K, Cellectar Biosciences, JUN 17, 2016, View Source [SID:1234513452]).

The preliminary in vivo study demonstrated that tumor uptake of CLR 1602’s paclitaxel payload increased by more than 30-fold over free paclitaxel, and also displayed an extended plasma half-life relative to free paclitaxel. The extended plasma half-life may, in part, explain the enhanced tumor uptake. Unlike free paclitaxel, which was rapidly cleared from plasma within 24 hours, CLR 1602 displayed prolonged retention even at 96 hours.

"The study results are a significant signal in the development of our paclitaxel Phospholipid Drug Conjugates (PDCs). More importantly, it represents further validation of our entire CLR CTX program," said Jim Caruso, president and CEO of Cellectar Biosciences. "These data clearly confirm our ongoing assertion that delivery of chemotherapeutics with our PDC platform may provide superior tumor cell targeting than chemotherapeutics alone, converting non-targeted chemotherapeutics into targeted cytotoxic agents. We anticipate conducting future studies and evaluating against other comparators, such as Abraxane."

The study was designed to assess the pharmacokinetics, absorption, and distribution after a single intravenous administration of CLR 1602, (N=24) a paclitaxel PDC vs. free paclitaxel (N=24) in tumor bearing mice. In this biodistribution study, CLR 1602, a paclitaxel Cremophor EL-free formulation (formulated without Cremophor, which is believed to contribute to free paclitaxel adverse event profile), was compared to free paclitaxel at equivalent sub-therapeutic concentrations in an effort to demonstrate enhanced CLR 1602 tumor targeting vs. free paclitaxel.

"This promising new in vivo paclitaxel data further confirms the tumor targeting selectivity of our PDC carrier, which has been consistently observed with oncology therapeutics and imaging agents. With targeting confirmed we will now optimize the PDC linker with the aim of enhancing the cytotoxic impact on cancer cells," said Jamey Weichert, Ph.D., founder and chief scientific officer of Cellectar Biosciences. "Furthermore, these results validate our ‘tool kit’ concept whereby carbon-14 labeled versions of our PDCs are utilized to quickly assess the potential tumor targeting enhancement that our PDC delivery system may afford to existing or new chemotherapeutic agents."

These quantitative results comparing biodistribution of CLR 1602 vs. free paclitaxel will be the subject of a poster presented at the 35th National Medicinal Chemistry Symposium in Chicago, June 26-29. The company also anticipates further data to be presented at another conference later this year.