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ARIAD’s AP26113 Receives FDA Breakthrough Therapy Designation For ALK+ Non-Small Cell Lung Cancer Resistant to Crizotinib

On October 2, 2014 ARIAD Pharmaceuticals reported that its investigational cancer medicine, AP26113, has received Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who are resistant to crizotinib (Press release Ariad, OCT 2, 2014, View Source [SID:1234500777]). This designation is based on results from the ongoing Phase 1/2 trial (NCT02094573) that show sustained anti-tumor activity of AP26113 in patients with ALK+ NSCLC, including patients with active brain metastases.

“We are very pleased that the FDA has granted Breakthrough Therapy designation to AP26113,” stated Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD. “We are encouraged by the clinical data on AP26113 that were presented recently at the European Cancer Congress, particularly in patients whose tumor had spread to the brain. We are focused on accelerating patient enrollment in the ongoing ALTA trial and on planning a front-line trial of AP26113 in treatment-naive patients.”

Phase 1/2 Data

Updated clinical data from the Phase 1/2 trial of AP26113 were recently shared at the 2014 European Cancer Congress. A total of 137 patients have been enrolled in the trial in the United States and Europe. Objective responses were observed in ALK+ NSCLC patients, and responses were observed in patients who were either TKI-naïve or resistant to crizotinib. Of the 72 ALK+ NSCLC patients evaluable for response, 52 (72%) demonstrated an objective response. The median duration of response was 49 weeks, and the median progression-free survival (PFS) was 56 weeks. In a subgroup analysis, 10 of 14 (71%) ALK+ NSCLC patients with active, untreated or progressing, brain metastases had evidence of radiographic improvement in those metastases. Of the seven evaluable TKI-naïve ALK+ NSCLC patients treated with AP26113, all demonstrated an objective response, including two complete responses (CR).

The most common adverse events (AEs), regardless of treatment relationship and including all grades, were nausea (45%), diarrhea (37%), and fatigue (37%). Adverse events, grade 3 or higher, occurring in three or more patients were dyspnea (4%), increased lipase (4%), hypoxia (4%), fatigue (3%), alanine aminotransferase (ALT) increased (2%) and amylase increased (2%). Serious AEs, all causality, occurring in three or more patients were dyspnea (7%), pneumonia (5%), hypoxia (4%), neoplasm progression (4%), pyrexia (2%) and pulmonary embolism (2%).

The 2012 Food and Drug Administration Safety and Innovation Act (FDASIA) established the Breakthrough Therapy designation to expedite the development and review of new drugs with preliminary clinical evidence demonstrating that they may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases. The Breakthrough Therapy designation is a distinct status from both accelerated approval and priority review, which can also be granted to the same drug if relevant criteria are met. As of September 3, 2014, FDA listed 213 total requests for Breakthrough Designation, and 61 requests were granted. Approximately 41% of the designated products are in cancer. (View Source).

(Press release, CanTx, OCT 1, 2014, View Source [SID:1234505854])

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Immunovaccine Announces Plans for Phase II Clinical Trial of DPX-Survivac in Patients with Recurrent Lymphoma

On October 1, 2014 Immunovaccine reported a clinical development program update for DPX-Survivac, the Company’s lead cancer vaccine candidate. Following the presentation of positive Phase I/II clinical trial data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2014 Annual Meeting earlier this year, the Company plans to advance DPX-Survivac into a Phase II clinical study in diffuse large B cell lymphoma (DLBCL) later this year (Press release Immunovaccine, OCT 1, 2014, View Source [SID:1234501176]). The trial will evaluate DPX-Survivac in combination with oral cyclophosphamide, an immune modulating agent, in patients with recurrent DLBCL. This combination therapy trial design fits with Immunovaccine’s clinical development strategy of maximizing therapeutic impact through concurrent treatment with various classes of promising immunotherapies.

"Our presentation of the first evidence of clinical activity for DPX-Survivac at the ASCO (Free ASCO Whitepaper) conference generated considerable interest from researchers around the world for studying the cancer vaccine in a range oncologic indications and with various combination approaches," said Dr. Marc Mansour, chief executive officer of Immunovaccine. "Following discussions with many key thought leaders and clinical researchers, we have outlined a clinical development strategy designed to generate meaningful data supporting the therapeutic benefit of DPX-Survivac in multiple cancer types with important unmet treatment needs. To this end, we are excited to initiate this trial in recurrent lymphoma, as well as studies in other cancer types, in the coming quarters."

The efficacy Phase II trial will launch at the Odette-Sunnybrook Cancer Centre with the expectation of adding additional sites in the coming months. Researchers will seek to enroll up to 24 patients, with the first patient expected to be dosed by early 2015. The open label study is designed to determine the objective response rate of patients with recurrent survivin-expressing DLBCL when treated with DPX-Survivac in combination with low dose oral cyclophosphamide. Immunovaccine expects to have initial clinical data from this study available approximately mid 2015. Positive clinical data from this study could provide rationale for the initiation of a pivotal trial in recurrent DLBCL.

Study investigators will monitor patients’ immune response to treatment and examine lymphoma deposit biopsies to evaluate immunological changes and gene expression profiles in the tumor. Additionally, the duration of patient clinical responses will also be documented in extended follow-up.

Lymphoma is a relevant oncologic target for DPX-Survivac as more than half of all aggressive non-Hodgkin’s lymphomas such as DLCBL express survivin, the tumor-associated antigen that serves as the basis for the vaccine. Furthermore, there is a growing body of clinical research that shows activity for immune modulatory agents such as cyclophosphamide in DLCBL. Importantly, lymphoma represents a significant unmet medical need as patients who are not transplant candidates or who experience recurrence following an autologous stem cell transplant (ASCT) lack additional treatment options.

"The promising results from the DPX-Survivac Phase I/Ib ovarian cancer studies, as well as expanding scientific literature highlighting the clinical activity of immune modulators in lymphoma, provide a strong scientific rationale for this study. There is a clear and important unmet medical need in this area of lymphoma management and we are eager to evaluate the potential of this combination therapy to deliver clinical benefit to those patients," said Neil Berinstein, M.D., Professor, Department of Medicine at the University of Toronto and medical oncologist at the Odette-Sunnybrook Cancer Centre, one of the sites at which the lymphoma trial will be conducted.

Ignyta Secures $31 Million Term Loan Facility from Silicon Valley Bank

On October 1, 2014 Ignyta reported that it has secured a $31 million term loan facility from Silicon Valley Bank (Press release Ignyta, OCT 1, 2014, View Source [SID:1234500806]). Under the loan facility, the company received initial funding of $21 million, approximately $11 million of which was used to repay the company’s existing loan with Silicon Valley Bank, and has a conditional option to receive an additional $10 million.

"This loan facility strengthens our balance sheet as we aggressively expand the clinical development of our highly promising lead program, RXDX-101, and continue the development of the rest of our precision medicine oncology pipeline," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "We appreciate the support Silicon Valley Bank has provided to us as we have grown."

The loan agreement, in addition to customary conditions, provides that the second tranche of $10 million may be drawn down by Ignyta at any time prior to September 30, 2015, provided that Ignyta has initiated the Phase IIa portion of the ongoing STARTRK-1 Phase I/IIa clinical study of its lead product candidate RXDX-101.

Ignyta will be required to pay interest on borrowings at the fixed, per-annum rate of 8.56% on a monthly basis through October 31, 2015. Thereafter, the company will be required to repay the principal plus interest in 30 equal monthly installments. The number of months of interest-only payments and the number of months over which the principal will be amortized will each be increased by six months if the second tranche has been drawn down or the company has raised sufficient funds through the offering of its capital stock, in each case prior to October 31, 2015.

8-K – Current report

On September 27, 2014 Endocyte reported that the small molecule drug conjugate (SMDC) vintafolide in combination with docetaxel extended overall survival (OS) for patients with folate receptor (FR) positive recurrent non-small cell lung cancer (NSCLC) compared to patients receiving monotherapy docetaxel in its TARGET Phase 2b clinical trial (Filing 8-K , Endocyte, OCT 1, 2014, View Source [SID:1234500798]). The late-breaking TARGET trial data will be presented today at the European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper), by Rohit Lal, M.D., consultant medical oncologist at Guys and St Thomas’ Hospital and an Honorary Consultant Medical Oncologist for Kings College Hospital, London.

The data show that patients in the predefined adenocarcinoma subgroup treated with the vintafolide plus docetaxel combination had a 27 percent reduction in risk of the disease worsening or death (HR=0.73, p=0.0899, one-sided test), and a 30 percent reduction in the risk of death (HR=0.70, p=0.1018) compared to docetaxel monotherapy. Stratified analysis, which adjusts for pre-defined patient characteristics in the trial, reflect a 49 percent reduction in the risk of death in patients with adenocarcinoma (HR=0.51, p=0.0147). These data include approximately 78 percent of the targeted number of events in the overall survival analysis. Overall survival in all patients, including those with squamous disease, reflect a 12 percent reduction in the risk of death (HR=0.88, p=0.2874) or 25 percent reduction when stratified (HR=0.75, p=0.1066). The primary endpoint of the study, as presented previously, showed that risk of disease worsening or death (progression-free survival, or PFS) was reduced by 25 percent for patients who received vintafolide plus docetaxel (HR=0.75, p=0.0696).

"We were pleased to see favorable results in the adenocarcinoma subgroup, where intensity of FR expression is approximately 20-fold higher than in squamous cell disease," said Ron Ellis, president and CEO at Endocyte. "We are currently evaluating the development plan for vintafolide in NSCLC in this patient population to determine if we will advance vintafolide quickly to a phase 3 trial after the OS data is fully mature. In the meantime, we continue to progress in the phase 1 studies of two other SMDCs. Our financial strength enables us to explore moving forward with more than one of our wholly-owned pipeline agents in select indications should it be the most beneficial path for the company and patients."

Dr. Rohit Lal said, "These results are very promising for patients receiving second-line treatment for this challenging disease. The folate receptor is a promising target, particularly in NSCLC, where the majority of patients are positive for this receptor. In particular, the consistency of results among patients with adenocarcinoma, including improved tumor response, delayed disease progression, and extended overall survival, support continued study of vintafolide in this patient population."

The study enrolled and treated 199 patients whose target tumors were all positive for the folate receptor, as determined with the companion imaging agent etarfolatide. Patients were randomized between three arms: vintafolide monotherapy, a combination of vintafolide and docetaxel, and docetaxel monotherapy. The independent data safety monitoring board determined before the completion of the trial that the vintafolide monotherapy arm was not likely to demonstrate increased benefit in the delay of disease progression compared to docetaxel alone.