On October 5, 2017 AVEO Oncology (NASDAQ:AVEO) reported the completion of a pre-planned futility analysis of the Phase 3 TIVO-3 trial, the Company’s randomized, controlled, multi-center, open-label study to compare FOTIVDA (tivozanib) to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC) (Press release, AVEO, OCT 5, 2017, View Source [SID1234520798]). Based on the results of the futility analysis, which was reviewed by an independent statistician, the study will continue as planned without modification. This analysis did not allow for early stopping due to efficacy to assure adequate follow-up for the key secondary endpoint of overall survival. The pre-planned futility analysis was triggered by the reporting of 128 progression events in early August. Additional events were recorded as part of the data management process leading into the futility analysis, resulting in a revised data cut-off date for the analysis of May 29. The Company continues to expect the TIVO-3 to read out in the first quarter of 2018.

The TIVO-3 trial, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support regulatory approval of tivozanib in the U.S. as a first and third line treatment for RCC.

“The treatment of advanced renal cell cancer is undergoing rapid change, with immunotherapy and combination regimens delivering improved outcomes for patients and shaping a new treatment paradigm,” said Michael Bailey, president and chief executive officer of AVEO. “We believe our tivozanib clinical strategy positions us well in this evolving landscape, with the TIVO-3 study on track to provide the first post-immunotherapy pivotal datasets for a VEGF-TKI, and the TiNivo study providing early and encouraging combination data. We look forward to readout of the TIVO-3 trial in the first quarter of 2018. We also look forward to presenting Phase 1 results from the Phase 1/2 TiNivo study of tivozanib in combination with OPDIVO at a medical conference this fall, and to leveraging tivozanib’s unique safety and efficacy profile in future potential therapy combinations.”

The TIVO-3 trial was designed to enroll patients with recurrent RCC who have failed at least two prior regimens, including VEGFR-TKI therapy (other than sorafenib). Eligible patients may also have received checkpoint inhibitor therapy in earlier lines of treatment. Patients are randomized 1:1 to receive either tivozanib or sorafenib, with no crossover between arms. The primary endpoint of the study is progression free survival. Secondary endpoints include overall survival, overall response rate, and safety and tolerability.

The TiNivo trial is a Phase 1/2 study of tivozanib in combination with Bristol-Myers Squibb’s OPDIVO (nivolumab), an immune checkpoint, or PD-1, inhibitor, for the treatment of RCC. The TiNivo trial is being led by the Institut Gustave Roussy in Paris under the direction of Bernard Escudier, MD, Chairman of the Genitourinary Oncology Committee. The trial advanced into the Phase 2 expansion portion following successful completion of the Phase 1 dose escalation portion. The combination was well tolerated to the full dose and schedule of single agent tivozanib, with no dose limiting toxicities. The expansion portion of the trial is expected to enroll an additional 20 subjects. Phase 1 results from the ongoing study have been submitted for presentation at a scientific meeting taking place in the fourth quarter.

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib has been investigated in several tumors types, including renal cell, colorectal and breast cancers.

On October 5, 2017 Amgen (NASDAQ:AMGN) reported that the Journal of Clinical Oncology has published positive results from the IMLYGIC (talimogene laherparepvec) Phase 2 ‘264 study (Press release, Amgen, OCT 5, 2017, View Source [SID1234520797]). The study met its primary endpoint of objective response rate (ORR), demonstrating that IMLYGIC in combination with YERVOY (ipilimumab) more than doubled ORR, defined as the proportion of patients with tumor size reduction, compared to ipilimumab alone in patients with unresectable stage IIIB-IV melanoma (39 percent versus 18 percent; odds ratio=2.9, 95 percent CI: 1.5, 5.5; p=0.002). Patients in the combination arm also experienced nearly double the complete response rate compared to ipilimumab alone (13 percent versus 7 percent).

“Advanced melanoma is highly aggressive and can require multiple treatment approaches over the course of the disease,” said Jason Chesney, M.D., lead author of the ‘264 study and director of the James Graham Brown Cancer Center, University of Louisville, Louisville, Ky. “Results from the study found that administration of IMLYGIC in combination with ipilimumab led to greater efficacy versus ipilimumab alone in both uninjected and visceral lesions. These data show that this combination of a checkpoint inhibitor plus IMLYGIC demonstrated a synergistic clinical effect and enhanced anti-tumor immune response in patients with metastatic melanoma.”

IMLYGIC is designed to rupture cancer cells causing the release of tumor-derived antigens, which along with granulocyte-macrophage colony-stimulating factor (GM-CSF), may help to initiate an anti-tumor immune response. However, the exact mechanism of action is unknown. This may be complementary to ipilimumab’s mechanism of action, as the blockade of cytotoxic T-lymphocyte-associated antigen-4 has been shown to augment activation and proliferation of tumor infiltrating T-effector cells.

Melanoma is one of the most dangerous types of skin cancers, especially when it spreads to other parts of the body.1 The study showed that responses occurred in both injected and uninjected lesions, including visceral lesions, demonstrating a systemic anti-tumor response. Thirty-one (32 percent) and 22 (22 percent) of the patients were shown to have visceral disease at baseline in the combination and ipilimumab arms, respectively. Of these patients, 16 (52 percent) in the combination arm and five (23 percent) in the ipilimumab arm were observed to have a decrease in visceral lesion tumor burden. Patients in the combination arm also experienced a median progression-free survival (PFS) of 8.2 months (median follow up 68 weeks) versus 6.4 months in the ipilimumab arm. The effect was not statistically significant (HR=0.83, 95 percent CI: 0.56, 1.23; p=0.35); however, the PFS analysis was not event-driven and is still ongoing. Evaluation of overall survival (OS) is ongoing and continues to be monitored.

The most common adverse events in the IMLYGIC plus ipilimumab arm compared to the ipilimumab alone arm were fatigue (59 percent versus 42 percent, respectively), chills (53 percent versus 3 percent, respectively), diarrhea (42 percent versus 35 percent, respectively), pruritus (40 percent versus 36 percent, respectively), rash (39 percent versus 28 percent, respectively) and nausea (38 percent versus 24 percent, respectively).

“IMLYGIC is the first and only approved oncolytic viral therapy in the U.S. and Europe, reinforcing Amgen’s leadership and commitment to developing innovative therapies for difficult-to-treat cancers,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “The data published today in the Journal of Clinical Oncology supports the scientific hypothesis behind the combination of IMLYGIC with an immune checkpoint inhibitor. We are excited about the promise of our diverse immuno-oncology pipeline that looks at combinations that may be effective in stimulating an immune attack on cancer cells.”

In the study, response rate was also higher in the combination arm across subsets of the disease. ORR for patients with stage IIIB/IIIC/IVM1a disease was 44 percent in the combination arm and 19 percent in the ipilimumab arm (overall response [OR]=3.3, 95 percent CI: 1.4, 7.8; p=0.007). In patients with stage IVM1b/IVM1c disease, ORR was 33 percent and 16 percent, respectively (OR=2.6, 95 percent CI: 0.9, 7.0; p=0.09). Among BRAF wild-type patients, ORR was 42 percent in the combination arm versus 10 percent in the ipilimumab arm (OR=6.5, 95 percent CI: 2.4, 17.4; p<0.0001). In patients with BRAF-mutant tumors, which comprised a minority of each arm at 35 (36 percent) and 34 (34 percent) for the combination and ipilimumab arms respectively, ORR was 34 percent in the combination arm versus 32 percent in the ipilimumab arm (OR=1.1, 95 percent CI: 0.4, 3.0; p=1.0). The disease control rate (DCR) was 58 percent in the combination arm and 42 percent in the ipilimumab arm (OR=1.9, 95 percent CI: 1.1, 3.4; p=0.033). DCR in all subgroups, with the exception of patients with BRAF mutations, favored the combination arm. About the '264 Study The '264 study is a Phase 1b/2, multicenter, open-label trial evaluating the safety and efficacy of IMLYGIC in combination with ipilimumab compared to ipilimumab alone in patients with unresectable stage IIIB-IV melanoma. The primary endpoint of the Phase 2 portion of study is ORR. Secondary endpoints include duration of response, DCR, PFS, OS and safety. The study randomized 198 patients, 98 in the IMLYGIC plus ipilimumab arm and 100 in the ipilimumab arm. About Metastatic Melanoma Melanoma remains a significant public health concern across the globe. Unlike some other cancers, melanoma incidence rates have doubled in the past 40 years, with 132,000 cases occurring worldwide each year.2,3 Melanoma is more dangerous than other skin cancers, especially when it spreads to other parts of the body, which is referred to as metastatic disease.1 The overall five-year risk of relapse after surgery increases as disease stage advances, from 48 percent for stage IIIA to 85 percent for stage IIIC.4 Risk of recurrence is even higher for patients in stage IV undergoing surgery, with 91 percent experiencing relapse.5 Despite new options, additional treatments are needed – particularly for patients with metastatic disease. About IMLYGIC (talimogene laherparepvec) IMLYGIC is a genetically modified herpes simplex type 1 virus that is injected directly into tumors. IMLYGIC replicates inside tumor cells and produces GM-CSF, an immunostimulatory protein. IMLYGIC then causes the cell to rupture and die in a process called lysis. The rupture of the cancer cells causes the release of tumor-derived antigens, which together with virally derived GM-CSF may help to promote an anti-tumor immune response. However, the exact mechanism of action is unknown. IMLYGIC is the first oncolytic viral therapy approved by the U.S. Food and Drug Administration (FDA) based on therapeutic benefit demonstrated in a pivotal study. IMLYGIC is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. IMLYGIC has not been shown to improve OS or have an effect on visceral metastases. Important U.S. Safety Information Contraindications Do not administer IMLYGIC to immunocompromised patients, including those with a history of primary or acquired immunodeficient states, leukemia, lymphoma, AIDS or other clinical manifestations of infection with human immunodeficiency viruses, and those on immunosuppressive therapy, due to the risk of life‐threatening disseminated herpetic infection. Do not administer IMLYGIC to pregnant patients. Warnings and Precautions Accidental exposure to IMLYGIC may lead to transmission of IMLYGIC and herpetic infection, including during preparation and administration. Health care providers, close contacts, pregnant women, and newborns should avoid direct contact with injected lesions, dressings, or body fluids of treated patients. The affected area in exposed individuals should be cleaned thoroughly with soap and water and/or a disinfectant. Caregivers should wear protective gloves when assisting patients in applying or changing occlusive dressings and observe safety precautions for disposal of used dressings, gloves, and cleaning materials. Exposed individuals should clean the affected area thoroughly with soap and water and/or a disinfectant. To prevent possible inadvertent transfer of IMLYGIC to other areas of the body, patients should be advised to avoid touching or scratching injection sites or occlusive dressings. Herpetic infections: Herpetic infections (including cold sores and herpetic keratitis) have been reported in IMLYGIC‐treated patients. Disseminated herpetic infection may also occur in immunocompromised patients. Patients who develop suspicious herpes-like lesions should follow standard hygienic practices to prevent viral transmission. Patients or close contacts with suspected signs or symptoms of a herpetic infection should contact their health care provider to evaluate the lesions. Suspected herpetic lesions should be reported to Amgen at 1-855-IMLYGIC (1-855-465-9442). Patients or close contacts have the option of follow-up testing for further characterization of the infection. IMLYGIC is sensitive to acyclovir. Acyclovir or other antiviral agents may interfere with the effectiveness of IMLYGIC. Consider the risks and benefits of IMLYGIC treatment before administering antiviral agents to manage herpetic infection. Injection Site Complications: Necrosis or ulceration of tumor tissue may occur during IMLYGIC treatment. Cellulitis and systemic bacterial infection have been reported in clinical studies. Careful wound care and infection precautions are recommended, particularly if tissue necrosis results in open wounds. Impaired healing at the injection site has been reported. IMLYGIC may increase the risk of impaired healing in patients with underlying risk factors (e.g., previous radiation at the injection site or lesions in poorly vascularized areas). If there is persistent infection or delayed healing of the injection site, consider the risks and benefits of continuing treatment. Immune-Mediated events including glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis, and vitiligo have been reported in patients treated with IMLYGIC. Consider the risks and benefits of IMLYGIC before initiating treatment in patients who have underlying autoimmune disease or before continuing treatment in patients who develop immune-mediated events. Plasmacytoma at the Injection Site: Plasmacytoma in proximity to the injection site has been reported in a patient with smoldering multiple myeloma after IMLYGIC administration in a clinical study. Consider the risks and benefits of IMLYGIC in patients with multiple myeloma or in whom plasmacytoma develops during treatment. Obstructive Airway Disorder: Obstructive airway disorder has been reported following IMLYGIC treatment. Use caution when injecting lesions close to major airways. Adverse Reactions The most commonly reported adverse drug reactions (≥ 25%) in IMLYGIC-treated patients were fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain. Pyrexia, chills, and influenza-like illness can occur at any time during IMLYGIC treatment, but were more frequent during the first 3 months of treatment. The most common Grade 3 or higher adverse reaction was cellulitis. Please see full Prescribing Information and Medication Guide for IMLYGIC.

On October 5, 2017 Teva Pharmaceuticals Europe BV, (NYSE and TASE: TEVA) reported the winner of the tomy’s (Teva’s Orphan hematological Malignancies award for Young hematologists) at the 7th International Symposium on Acute Promyelocytic Leukemia (APL) in Rome, Italy last week (Press release, Teva, OCT 5, 2017, View Source [SID1234520796]). During the event entitled, ‘Next-Generation APL Leaders: Teva’s Award for Young Hematologists’ Dr. Salamero was awarded a tomy’s trophy, as well as a bursary to attend the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in the USA in December.
This press release features multimedia.

Dr. Salamero is currently a hematologist at the Vall d’Hebron University Hospital, Barcelona, Spain and presented research entitled Very elderly acute promyelocytic leukemia: a multicentric experience. The study selected patients aged ≥ 75 years old with APL who had reported to PETHEMA registry (Spanish Hematology Treatment Programme) over the last nineteen years. Epidemiologic characteristics and disease features in the very elderly APL population were analysed and the percentage of patients treated according to investigators criteria described. The research found that patients treated with all-trans retinoic acid (ATRA) plus anthracycline-based regimen showed better outcomes than patients who received other strategies, such as ATRA alone, chemotherapy alone or best supportive care.

Speaking after the awards ceremony, Dr. Salamero said, “Winning the tomy’s – it’s been a pleasure. I feel proud, not because of my work but the work of the PETHEMA group. I would recommend attending the APL Symposium as not only is it very interesting, but it facilitates a lot and keeps you in touch with your peers.”

The tomy’s are an educational award programme for young hematologists, sponsored by Teva Oncology. The awards are open to young hematologists, or young physicians training to become hematologists aged 40 years or younger. The entrants are challenged to illustrate the latest scientific advancements in the management of orphan hematological malignancies by presenting a case study or case series demonstrating their excellence in education and presentation skills. The independent jury for the 2017 tomy’s was comprised of experts in orphan hematological malignancies and includes Pierre Fenaux, France; Richard Schlenk, Germany; Francesco Lo-Coco, Italy; Bob Löwenberg, Netherlands; Nigel Russell, UK and Miguel Sanz, Spain.

“It’s estimated that between 1,500 – 2,000 people in Europe are diagnosed with APL each year. Even though APL is the most lethal type of acute leukemia, it’s highly curable and more research into this disorder is urgently needed. The tomy’s programme reflects Teva’s commitment to encouraging new and innovative research aimed at improving patient outcomes in orphan hematological malignancies,” said Paul Harmon, Head of Teva’s Oncology Care and Transplant Europe.

“APL can cause a number of symptoms including uncontrollable bleeding and can kill within hours or days if left untreated. As it’s so rare, APL can be difficult to recognise and diagnose. We’re excited about this programme, and we believe it will stimulate new exciting research, with the ultimate ambition of saving lives,” commented Prof. Lo-Coco, tomy jury member.

The full list of finalists as well as more information on the jury can be accessed via: View Source
The tomy’s awards ceremony in Rome follows the inaugural tomy’s awards, announced at the Teva Oncology Satellite Symposium at the Acute Leukemias XVI International Symposium, which took place in Munich, Germany, in February 2017.

For more information on the Tomy’s awards or for queries regarding abstract submissions or notifications, please contact: [email protected].

On October 5, 2017 Pfizer reported that they unveils enhanced offerings to help patients manage their life with cancer (Press release, Pfizer, OCT 5, 2017, View Source [SID1234520795]). Pfizer Oncology Together is a first-of-its-kind program for patients taking Pfizer Oncology medicines that offers dedicated social workers called ‘Care Champions’ to help navigate the complexities that accompany treatment, such as identifying resources to help find emotional support, and workplace transition, transportation and financial assistance. For cancer patients taking a Pfizer Oncology medicine, please visit www.PfizerOncologyTogether.com.

Pfizer is also proud to launch This is Living with Cancer, a program that provides tools and resources to support those who have been affected by cancer, including a mobile app, LivingWith, designed to help manage some of the daily challenges faced by people living with cancer. For more information about the program and to find out more about LivingWith, visit www.ThisIsLivingWithCancer.com.

“Today, more than 15 million people in the United States are living with cancer and that number is expected to grow as emerging science and better therapies are likely to increase the number of patients living with cancer as we strive for a cure,” said Liz Barrett, Global President, Pfizer Oncology. “Navigating life with cancer poses many challenges for patients and their families and friends, and we hope these unique programs can help their journey.”

“Cancer patients can feel isolated and unsure about how to navigate care and approach day-to-day life,” said Myra Biblowit, President & CEO, Breast Cancer Research Foundation. “Pfizer’s new programming that goes beyond treatment is critical in helping patients and their care networks deal with the challenges associated with living with cancer.”

About Pfizer Oncology Together

Pfizer Oncology Together is a portfolio-wide program for patient access solutions and support in the U.S. As part of the program, patients receiving Pfizer Oncology medicines will have access to a team of social workers who will be able to provide support beyond the traditional access and reimbursement services by connecting them with a wide variety of patient education resources and outreach programs. The support programs include identifying independent third party resources that provide emotional support, lodging, transportation, workplace transition support for patients balancing their jobs and treatment, and connecting patients and their families to local advocacy groups. This service will provide patients and caregivers with a dedicated representative over the course of their treatment. For more information go to www.PfizerOncologyTogether.com or call 1-877-744-5675.

About This is Living with CancerTM and LivingWith

LivingWith provides patients and caregivers with a tool to organize certain important information in one place, including:

Build a network of support from friends and family to get help with daily tasks
Record and remember important information from doctor visits
Track mood, pain and connect with wearables
Get organized and store key documents
Receive information about local events and nutrition articles
LivingWith is available at no charge and can be downloaded at the Apple App store or Google Play.

On October 5, 2017 TG Therapeutics, Inc. (NASDQ:TGTX), reported that the first patient has been dosed in a Phase 1 clinical trial evaluating the safety and tolerability of its proprietary fully-human anti-PD-L1 monoclonal antibody. This first-in-human, Phase I, open-label, multicenter study is evaluating the safety and tolerability of ascending doses of our anti-PD-L1 monoclonal antibody in checkpoint therapy-naïve patients with selected recurrent or metastatic cancers. Secondary endpoints for this study include the evaluation or characterization of the pharmacokinetics, immunogenicity and preliminary efficacy (Press release, TG Therapeutics, OCT 5, 2017, View Source [SID1234520789]). This study will initially enroll patients in sites across Australia and New Zealand.

Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, “We are excited to bring our first immuno-oncology asset into clinical development. This first-in-human study is being conducted in solid tumors to expedite enrollment and enrich for patients most likely to respond to anti-PD-L1 therapy. Once a recommended Phase 2 dose is identified, we plan to commence a study in B-cell malignancies both as a single agent and in combination with our other pipeline products. We have already piloted the concept by combining our proprietary ‘U2′ (TG-1101 + TGR-1202) regimen with the PD-1 inhibitor, pembrolizumab, and believe that experience will speed the development of our proprietary triplet.” Mr. Weiss continued, “As always, our vision is to develop best-in-class combination therapies and we believe adding PD-1/PD-L1 therapy to targeted therapy represents the next generation of treatment options for patients with B-cell malignancies. Advancing our proprietary anti-PD-L1 into the clinic is an important first step in reaching this goal.”