1stOncology™: Cancer Intelligence Service – Page 15641 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Adaptimmune Announces FDA Acceptance of IND Application for Affinity Enhanced T-Cell Therapy Targeting AFP in Liver Cancer

On April 07, 2016 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in the use of TCR engineered T-cell therapy to treat cancer, reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s investigational new drug (IND) application for autologous genetically modified T-cells expressing affinity enhanced T-cell receptors (TCRs) specific for alpha fetoprotein (AFP) in patients with locally advanced or metastatic hepatocellular carcinoma, the sixth most common cancer worldwide (Press release, Adaptimmune, APR 7, 2016, View Source [SID:1234510500]). The IND is now active.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

This will be Adaptimmune’s second wholly-owned therapeutic candidate to enter clinical trials. The company initiated a study in December 2015 to evaluate its unpartnered T-cell therapy targeting the MAGE-A10 cancer antigen in patients with non-small cell lung cancer.

The acceptance of this IND allows Adaptimmune to initiate an open label Phase I study designed to evaluate the safety and anti-tumor activity of its AFP therapeutic candidate in hepatocellular carcinoma (HCC). Site selection activities are under way, and the company anticipates that enrollment will commence in the second half of 2016.

"Hepatocellular carcinoma is one of the most common and deadly types of cancer in the world and it represents a significant unmet medical need, as there is a dearth of effective therapies for advanced disease," said Rafael Amado, Adaptimmune’s Chief Medical Officer. "We are pleased to initiate clinical evaluation of our AFP T-cell therapeutic candidate in this patient population."

AFP is believed to be highly expressed in approximately 30 percent of hepatocellular carcinomas. Expression has been shown to be absent or very low in most adult non-reproductive tissues and will be evaluated prior to enrollment. Adaptimmune’s proprietary technology enables the company to routinely generate TCRs which address intracellular targets, such as AFP, that are not accessible to other therapies.

This will be a Phase I open label clinical trial evaluating the safety and anti-tumor activity of autologous T-cells expressing enhanced TCRs specific for AFP in HLA-A2 positive subjects with advanced HCC. The study will enroll up to 30 subjects with measurable, histologically confirmed HCC, not amenable to resection or loco-regional therapy, and progressive disease following (or intolerant of or refuses) sorafenib treatment. The primary objective of the study is to evaluate the safety and tolerability of this therapy in subjects with AFP-positive HCC. Additional objectives include anti-tumor activity, persistence of genetically modified cells in the body, and evaluation of the phenotype and functionality of genetically modified cells isolated from peripheral blood or tumor post infusion.

Ludwig Cancer Research and the Cancer Research Institute Initiate Clinical Trial of a Novel Combination Immunotherapy For Ovarian Cancer

On April 6, 2016 Ludwig Cancer Research and the Cancer Research Institute (CRI) reported that they have launched a Phase 1/2 clinical trial of combination immunotherapy for advanced ovarian cancer (Press release, Cancer Research Institute, APR 6, 2016, View Source [SID:1234510534]). The international, multicenter trial is led by George Coukos, director of the Ludwig Institute for Cancer Research, Lausanne and Brad Monk, director of Gynecologic Oncology at St. Joseph’s Hospital and Medical Center. The study is being conducted through the CVC Trials Network, which is jointly managed by Ludwig and CRI, in collaboration with MedImmune, the global biologics research and development arm of AstraZeneca, and the biopharmaceutical company VentiRx Pharmaceuticals Inc.

"Ludwig has long supported the design and evaluation of new therapeutic strategies to improve the treatment options available to cancer patients," said Jonathan Skipper, Ludwig’s executive vice president of Technology Development. "Employing immunotherapies in combination holds great promise in that endeavor. We are proud to be a part of this effort to bring investigational drugs being developed by different commercial partners to a single clinical trial and improve the standard of care for recurrent ovarian cancer, a disease for which patients today have few treatment options."

The open-label trial is evaluating the combination of MedImmune’s investigational antibody cancer drug durvalumab, a PD-L1 inhibitor, and VentiRx’s investigational TLR8 agonist motolimod added to chemotherapy in locally advanced or recurrent ovarian cancers that have become resistant to platinum chemotherapy. Both of the investigational drugs have been found in other studies to have acceptable safety profiles when used alone.

The researchers expect that motolimod’s activation of TLR8 will create conditions within tumors that are optimal to enhancing the effects of durvalumab. Further, when given with chemotherapy, motolimod could boost immune responses against cancer cells that are not engaged by durvalumab by helping the immune system "see" cancer antigens. Since the two immunotherapies work in distinct ways, they could have additive effects, inducing more potent and durable anti-tumor immune responses.

"This study is a good example of what’s possible when researchers have access to new therapies and are permitted to test hypotheses supported by the most recent science," said Ludwig Lausanne director George Coukos. "We are hopeful that the combined therapies we are testing in this trial will be of great benefit to ovarian cancer and other cancer patients."

Patients enrolled in the trial will be treated with the chemotherapeutic drug pegylated liposomal doxorubicin (PLD), which is the current standard of care for ovarian cancer after the failure of platinum therapy. They will also receive durvalumab and motolimod, with the Phase 1 and 2 portions of the trial running successively. The primary objective of the Phase 1 cohort of the study is to evaluate the safety and optimal dosage of the combination. The Phase 2 cohort of the trial will measure the efficacy of the treatment by evaluating the number of patients whose tumors have not progressed at six months.

Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1). PD-L1 expression enables tumours to evade detection from the immune system through binding to PD-1 on cytotoxic T lymphocytes. Durvalumab blocks PD-L1 interaction with both PD-1 and CD80 on T cells, countering the tumour’s immune-evading tactics. Durvalumab is being developed, alongside other immunotherapies, to empower the patient’s immune system and attack the cancer. Durvalumab is being investigated in an extensive clinical trial program, as monotherapy or in combination with tremelimumab, in NSCLC, bladder, head and neck, gastric, pancreatic, HCC and blood cancers.

Motolimod binds and activates Toll-like receptor 8 (TLR8), which is found in a variety of immune cells and serves as a key initiator of the innate immune response. Notably, it is expressed by myeloid dendritic cells, which help direct and boost T cell responses against infectious agents and cancers. Motolimod has been shown to be safe when combined with PLD in a previous study on ovarian cancer, with evidence of clinical benefit. The motolimod-PLD combination is currently under evaluation in a large, randomized, placebo-controlled phase 2 clinical study in patients with ovarian cancer.

"This clinical trial is part of a larger clinical research program supported by Ludwig and CRI to speed the evaluation of novel cancer immunotherapies, alone or in combination with other cancer drugs," said Adam Kolom, managing director of CRI’s Clinical Accelerator, which funds the trials. "All of the studies have, as additional objectives, the collection of genetic and immunologic data derived from clinical samples that are obtained from patients. Such information will provide clues to the impact of the evaluated therapies and suggest refined or new strategies for treating cancer."

Pfizer Announces Termination Of Proposed Combination With Allergan

On April 6, 2016 Pfizer Inc. (NYSE: PFE) reported that the merger agreement between Pfizer and Allergan plc (NYSE: AGN) has been terminated by mutual agreement of the companies (Press release, Pfizer, APR 6, 2016, View Source [SID:1234510532]). The decision was driven by the actions announced by the U.S. Department of Treasury on April 4, 2016, which the companies concluded qualified as an "Adverse Tax Law Change" under the merger agreement.

"Pfizer approached this transaction from a position of strength and viewed the potential combination as an accelerator of existing strategies," stated Ian Read, Chairman and Chief Executive Officer, Pfizer. "We remain focused on continuing to enhance the value of our innovative and established businesses. Our most recent product launches, including Prevnar 13 in Adults, Ibrance, Eliquis and Xeljanz, have been well-received in the market, and we believe our late stage pipeline has several attractive commercial opportunities with high potential across several therapeutic areas. We also maintain the financial strength and flexibility to pursue attractive business development and other shareholder friendly capital allocation opportunities."

"We plan to make a decision about whether to pursue a potential separation of our innovative and established businesses by no later than the end of 2016, consistent with our original timeframe for the decision prior to the announcement of the potential Allergan transaction," continued Read. "As always, we remain committed to enhancing shareholder value."

In connection with the termination of the merger agreement, Pfizer has agreed to pay Allergan $150 million for reimbursement of expenses associated with the transaction.

As previously announced, Pfizer plans to report its First-Quarter 2016 financial results on May 3, 2016.

Giotrif® (afatinib) approved in Europe as new oral treatment option for patients with squamous cell carcinoma of the lung

On April 7, 2016 Boehringer Ingelheim reported that the European Commission (EC) has granted marketing authorisation for Giotrif (afatinib) for the treatment of patients with advanced squamous cell carcinoma (SqCC) of the lung whose disease has progressed on or after treatment with platinum-based chemotherapy(Press release, Boehringer Ingelheim, APR 6, 2016, View Source [SID:1234510494]). Afatinib is already approved for the treatment of patients with EGFR mutation-positive non-small cell lung cancer (NSCLC).*

Dr. Mehdi Shahidi, Medical Head, Solid Tumour Oncology, Boehringer Ingelheim commented: "Whilst there have been some recent and significant advances in the treatment of squamous cell carcinoma of the lung, the intravenous administration and frequent visits to the hospital can be a challenge for patients often debilitated by this disease. In this context and supported by robust evidence from a Global head-to-head Phase III study, we are pleased to offer an effective oral treatment option for patients suffering from this type of lung cancer to the European market."

SqCC of the lung is associated with a poor prognosis, limited survival and symptoms like cough and dyspnoea. The median overall survival (OS) after diagnosis of advanced SqCC is around one year.4,5

The marketing authorisation in Europe is valid for 28 countries within the EU. The EU regulatory submission was based on results of the head-to-head LUX-Lung 8 trial in patients with SqCC of the lung whose tumours progressed on or after first-line chemotherapy. Afatinib, compared to erlotinib, demonstrated:3

Significant delay in progression of lung cancer (PFS, progression-free survival, primary endpoint), reducing the risk of cancer progression by 19%
Significant improvement in overall survival (OS, key secondary endpoint), reducing the risk of death by 19%
Significantly improved disease control rate (51% vs 40%; P=0.002)
An improvement in quality of life and control of cancer symptoms
The rate of severe adverse events was similar between the two treatment arms with differences observed in the incidence of certain side effects: a higher incidence of severe diarrhoea and stomatitis (mouth sores) was observed with afatinib compared to erlotinib (grade 3 diarrhoea: 10% vs 2%; grade 3 stomatitis: 4% vs 0%), while a higher incidence of severe rash/acne was reported with erlotinib compared to afatinib (grade 3 rash/acne: 10% vs 6%).3

LUX-Lung 8 (NCT01523587) is part of the afatinib LUX-Lung programme – the largest collection of clinical trials of any EGFR tyrosine kinase inhibitor (TKI), with over 3,760 patients across eight studies conducted across the world. The comprehensive LUX-Lung programme includes two pivotal studies in the first-line setting for EGFR mutation-positive patients, LUX-Lung 3 and 6 which compared afatinib to chemotherapy regimens. In addition, the programme included two head-to-head studies (LUX-Lung 7 and 8) of afatinib versus first-generation EGFR TKIs. The LUX-Lung programme has involved over 680 sites in 40 countries, reflecting the strong partnership between Boehringer Ingelheim and the lung cancer specialist community.

Afatinib is already approved in over 60 countries for the first-line treatment of EGFR mutation-positive NSCLC*, and recent results from the LUX-Lung 7 trial positively underscore the benefits of afatinib versus gefitinib, another first-generation EGFR targeting agent in this indication.6 Results of this global Phase IIb head-to-head trial demonstrated afatinib was superior in reducing the risk of lung cancer progression and the risk of treatment failure both by 27% compared to gefitinib.6

For more information about the LUX-Lung 8 trial, please see Professor Jean-Charles Soria’s publication in The Lancet Oncology

*Afatinib is approved in the EU under the brand name GIOTRIF for the first-line treatment of TKI naïve adult patients with advanced EGFR mutation-positive NSCLC. In April 2016 afatinib was approved by the European regulatory authority as a second-line treatment for SqCC of the lung. Registration conditions differ internationally, please refer to locally approved prescribing information.

TESARO Announces Global Prostate Cancer Collaboration and Licensing Agreement With Janssen

On April 06, 2016 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, and Janssen Biotech Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, reported a global collaboration and license agreement focused on the development and commercialization of niraparib specifically for the treatment of prostate cancer (Press release, TESARO, APR 6, 2016, View Source [SID:1234510485]). Niraparib is an oral, once daily, potent, and highly selective PARP inhibitor that is currently being evaluated in Phase 3 clinical trials for ovarian and breast cancer.

"We are pleased to be working with Janssen, a leader in the prostate cancer field, to advance niraparib in this indication," said Lonnie Moulder, CEO of TESARO. "This innovative, indication-specific collaboration accelerates efforts to expand the treatment options available for men with prostate cancer and further increases the value of the niraparib franchise."

Under the terms of the agreement, Janssen will develop and commercialize niraparib for patients with prostate cancer worldwide, except in Japan. TESARO will receive an upfront payment of $35 million, and is eligible to receive additional milestone payments of up to $415 million, contingent upon Janssen reaching certain pre-determined development, regulatory and commercial milestones, in addition to tiered, double-digit royalty payments. Janssen will be responsible for funding all development and commercialization activities related to niraparib in prostate cancer. Separately, Johnson & Johnson Innovation — JJDC, Inc. is making a $50 million equity investment in TESARO at a price of $44.24 per share, which is based upon the 5-day volume weighted average share price through the day prior to execution of the agreement.

About Niraparib

Niraparib is an oral, once daily, potent, and highly selective PARP inhibitor that induces synthetic lethality in tumors cells with homologous recombination DNA repair deficiencies (HRD). The ongoing development program for niraparib includes a Phase 3 trial in patients with ovarian cancer (the NOVA trial), a registrational Phase 2 treatment trial in patients with ovarian cancer (the QUADRA trial), and a Phase 3 trial for the treatment of patients with BRCA-positive breast cancer (the BRAVO trial). In addition, a Phase 3 trial of niraparib in first-line ovarian cancer (PRIMA) and a Phase 1/2 clinical trial designed to evaluate the combination of niraparib plus KEYTRUDA (pembrolizumab) in patients with triple-negative breast cancer or ovarian cancer are planned to initiate shortly. Several collaborator-sponsored studies are also underway, including combination trials of niraparib plus enzalutamide, bevacizumab, and temozolomide, in patients with prostate cancer, ovarian cancer, and Ewing’s sarcoma, respectively. Additional studies are being planned to evaluate niraparib in patients with lung cancer.