On November 23, 2015 NewLink Genetics Corporation (NLNK), a biopharmaceutical company at the forefront of discovering, developing and commercializing novel immuno-oncology product candidates, including both cellular immunotherapy and checkpoint inhibitor platforms, to improve the lives of patients with cancer, reported a trial update from a Phase 1b/2 study of indoximod in combination with temozolomide presented on November 20 at the 20th Annual Scientific Meeting of the Society for Neuro-Oncology in San Antonio, Texas (Press release, NewLink Genetics, NOV 23, 2015, View Source [SID:1234508326]).

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Indoleamine 2,3-dioxygenase (IDO) is a key immuno-modulatory enzyme that allows tumors to thwart the host immune response and therefore is an important research target. IDO is expressed in a large proportion of solid tumors, including 50-90% of glioblastoma tumors. Indoximod is NewLink Genetics’ proprietary product candidate that has shown the potential to interfere with multiple targets within the IDO pathway and thereby to unleash the immune system to fight cancer.

The update presented is from a Phase 1b/2 study of indoximod in combination with temozolomide in patients with advanced glioblastoma who have previously demonstrated that their tumors are refractory to temozolomide. The completed Phase 1b portion of the study, which enrolled 12 patients, continues to show that the combination has an acceptable safety profile, confirming data previously presented. This Phase 1b portion of the study also demonstrated preliminary efficacy of the combination therapy. A six-month progression free survival (PFS) rate of 25% was observed, which compares favorably to the historical rate of 15% for refractory glioblastoma. In addition, the patient previously reported as having achieved a radiographically confirmed partial response (PR) remains on study treatment and has thus far demonstrated a durable response of greater than eight months, with an overall survival on trial of 20 months.

The Phase 2 portion of the study, which aims to determine the preliminary efficacy of the combination therapy, has enrolled 40 of a planned 132 patients as of the data cutoff. Nine of the 40 patients have been enrolled for more than six months and seven are evaluable as to outcome. One of these seven patients has demonstrated a radiographically confirmed PR after previously being refractory to treatment with temozolomide. The objective response occurred after having stable disease on treatment for six months. Of note, the onsets of the two partial responses, one in Phase 1b and one in Phase 2, were delayed, suggesting a possible immunotherapy-based mechanism of response.

"It is encouraging to see some promising early signs of activity of this combination of an immunotherapy with standard chemotherapy in recurrent GBM, which is a disease with huge unmet need," said Howard Colman, MD, PhD, Associate Professor of Neurosurgery and Director of Medical Neuro-Oncology at the Huntsman Cancer Institute at the University of Utah and an author of the study.

"I am particularly impressed with the potential early signals of an immune-mediated effect, as evidenced by the delayed onset and durability of the responses observed," said Olivier Rixe, MD, PhD, Professor of Medicine and Associate Director for Clinical Research at the University of New Mexico Comprehensive Cancer Center and an author of the study. "This is one of the first clinical trials testing an immune checkpoint inhibitor in glioblastoma. It shows that indoximod is the first such therapy to produce an objective response in glioblastoma."

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"We are pleased with the preliminary safety and efficacy data on the combination of indoximod and temozolomide in glioblastoma obtained so far in this study," said Nicholas Vahanian, M.D., President and Chief Medical Officer. "We look forward to learning more about indoximod in our clinical studies in glioblastoma and four other cancer types, as well as about our six other immuno-oncology products currently in clinical testing."

On November 23, 2015 The U.S. Food and Drug Administration reported that it approved Opdivo (nivolumab) to treat patients with advanced (metastatic) renal cell carcinoma, a form of kidney cancer, who have received a certain type of prior therapy.
"Opdivo provides an important therapy option for patients with renal cell carcinoma," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research (Press release, , NOV 23, 2015, View Source [SID:1234508328]). "It is one of few therapies that have demonstrated the ability to extend patients’ survival in treating this disease." Torisel (temsirolimus), approved in 2007, is the only other FDA-approved therapy that has demonstrated overall survival in renal cell cancer.

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Renal cell carcinoma is the most common form of kidney cancer in adults and forms in the tissues of the kidney that make urine. The National Cancer Institute estimates 61,560 new cases and 14,080 deaths from kidney and renal pelvis cancer in the United States this year.

"Additionally, Opdivo’s extended indication, from melanoma and non-small cell lung cancer to renal cell cancer, demonstrates how immune therapies can benefit patients across a wide range of tumors," continued Dr. Pazdur.

Opdivo works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, Opdivo may help the body’s immune system fight cancer cells. Opdivo is intended for use in renal cell carcinoma in patients who have received prior anti-angiogenic therapy (treatments that interfere with the blood vessels that contribute to the growth of cancerous cells).

The safety and efficacy of Opdivo for this use were demonstrated in an open-label, randomized study of 821 patients with advanced renal cell carcinoma whose disease worsened during or after treatment with an anti-angiogenic agent. Patients were treated with Opdivo or another type of kidney cancer treatment called everolimus (marketed as Afinitor). Those treated with Opdivo lived an average of 25 months after starting treatment compared to 19.6 months in those treated with Afinitor. This effect was observed regardless of the PD-L1 expression level of patients’ renal cell tumors. Additionally, 21.5 percent of those treated with Opdivo experienced a complete or partial shrinkage of their tumors, which lasted an average of 23 months, compared to 3.9 percent of those taking Afinitor, lasting an average of 13.7 months.

The most common side effects of Opdivo for this use are conditions relating to abnormal weakness or lack of energy (asthenic conditions), cough, nausea, rash, difficulty breathing (dyspnea), diarrhea, constipation, decreased appetite, back pain and joint pain (arthralgia).

Opdivo also has the potential to cause serious side effects that result from the immune system effect of Opdivo (known as "immune-mediated side effects"). These severe immune-mediated side effects involve healthy organs, including the lung, colon, liver, kidneys, hormone-producing glands and the brain.

The FDA granted the Opdivo application a breakthrough therapy designation, fast track designation, and priority review status. These are distinct programs intended to facilitate and expedite the development and review of certain new drugs in light of their potential to benefit patients with serious or life-threatening conditions.

Opdivo is marketed by Bristol-Myers Squibb based in Princeton, New Jersey. Torisel is marketed by Pfizer, based in New York, New York. Afinitor is marketed by Novartis Pharmaceuticals of East Hanover, New Jersey.

On November 24, 2015 CTI BioPharma Corp. (CTI BioPharma or the Company) (NASDAQ and MTA: CTIC) reported that the United Kingdom’s National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group has chosen to advance tosedostat, the Company’s investigative oral aminopeptidase inhibitor, to the second stage of a randomized clinical trial of low-dose cytarabine plus or minus tosedostat in older patients with Acute Myeloid Leukemia (AML) or high risk Myelodysplastic Syndrome (MDS) (Press release, CTI BioPharma, NOV 23, 2015, View Source;p=RssLanding&cat=news&id=2116992 [SID:1234508332]). The AML Less Intensive (LI-1) trial is designed as a "Pick-a-Winner" trial to be able to simultaneously test a number of promising agents added to standard therapy with low-dose cytarabine in older patients with AML or MDS who are unfit for standard aggressive induction therapy. Nine regimens have been tested in the Pick-a-Winner program, of which only 4, including tosedostat, have passed the initial hurdle for progression (which requires evidence of an improvement in remission rate with acceptable safety). The ultimate aim of the trial is to identify treatments that can double the 2-year survival of patients in this group. Based on the randomized Phase 2 interim analysis, the trial management group determined that tosedostat should proceed to the next stage of the study. It is anticipated that an additional 110 patients will be required in such phase. A further evaluation will take place before the intended expansion to a 400 patient Phase 3 trial.

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Tosedostat is a potential first-in-class selective inhibitor of aminopeptidases, which are enzymes required by some tumor cells, but not normal cells, to provide a source of amino acids necessary for growth and tumor cell survival.

"A large portion of older patients and patients with comorbid conditions are poorly suited for conventional intensive chemotherapy due to a high rate of treatment-related mortality. For these patients, there is a significant unmet need for effective and well tolerated alternative therapies," said Jack Singer, M.D., Chief Scientific Officer of CTI BioPharma. "We are pleased that tosedostat has been selected to continue in this trial and is moving forward to the next stage. Tosedostat has demonstrated encouraging clinical activity in three prior Phase 2 studies in both first-line AML in older patients and in patients who relapsed following standard therapies. Tosedostat is an oral agent given once daily on an outpatient basis that has not been associated with drug-related blood count suppression."

About the LI-1 Trial
In this Phase 2/3 trial, referred to as the AML Less Intensive (LI-1) trial, patients are randomized to standard treatment with low dose cytarabine, versus several investigational treatments – each usually in combination with low dose cytarabine. This is called a "Pick-a-Winner" trial design. Under this design, the Phase 2 portion of the trial initially randomized 50 patients per arm, and, if the complete response rate of cytarabine plus novel therapy appeared satisfactory, the randomization continues to the next stage usually with an additional 50 patients per arm. There is then a further assessment by the data monitoring committee to allow the trial to continue to the final stage in which case up to a total of approximately 200 patients per arm would be enrolled. Overall survival will serve as the primary endpoint of the trial. The NCRI Haematological Oncology Clinical Studies Group under the sponsorship of Cardiff University is conducting the trial.

About Tosedostat
Tosedostat is an oral aminopeptidase inhibitor that has demonstrated anti-tumor responses in blood-related cancers and solid tumors in Phase 1-2 clinical trials. Tosedostat is currently being evaluated in multiple Phase 2 clinical trials for the treatment of patients with AML or high-risk MDS. Tosedostat is not approved or commercially available.

About Acute Myeloid Leukemia and Myelodysplastic Syndrome
AML is the most common acute leukemia affecting adults, and its incidence increases with age. In older patients, AML may occur de novo or secondary to prior anti-cancer therapy, or from progression of other diseases, such as myelodysplasia. AML is a cancer characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age.1 The symptoms of AML are caused by the replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets, and normal white blood cells, leading to infections and bleeding. AML progresses rapidly and is typically fatal within weeks or months if left untreated. In 2015, approximately 20,830 new cases of AML are expected to be diagnosed in the United States and an estimated 10,460 are expected to die from the disease.2 While AML may occur at any age, adults at least 60 years of age are more likely than younger people to develop the disease.2 Although a substantial proportion of younger individuals who develop AML can be cured, AML in the elderly typically responds poorly to standard therapy with few complete remissions.

AML may develop from the progression of other diseases, such as MDS. MDS are a group of diverse bone marrow disorders in which the bone marrow does not produce enough healthy blood cells. MDS is often referred to as a "bone marrow failure disorder."

On November 23, 2015 Genmab A/S (OMX: GEN) reported that the Phase III study of single agent ofatumumab compared to single agent rituximab in patients with follicular non-Hodgkin’s lymphoma (NHL) that has relapsed at least 6 months after completion of treatment with a rituximab-containing regimen will be stopped early (Press release, Genmab, NOV 23, 2015, View Source [SID:1234508333]). The decision to stop the study was made after a planned interim analysis performed by an Independent Data Monitoring Committee (IDMC) showed that it was unlikely that ofatumumab would show superiority if the trial was to be completed as planned.

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"The outcome of the interim analysis in this study is disappointing as we had hoped to see superiority of ofatumumab. The data from the study will now be prepared so that it can be presented at a future scientific conference," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Today’s news does not impact any other ongoing studies with ofatumumab.

About the study
This Phase III study aimed to randomize up to 516 patients to receive ofatumumab (1000 mg) or rituximab (375 mg/m2) by intravenous infusion for four weekly doses. Patients who had stable or responsive disease then received single infusions of ofatumumab or rituximab every two months for four additional doses for a total of eight doses over nine months. The primary endpoint of the study was progression free survival.

About Ofatumumab (Arzerra)
Ofatumumab is a human monoclonal antibody that is designed to target the CD20 molecule found on the surface of chronic lymphocytic leukemia (CLL) cells and normal B lymphocytes.

In the United States, Arzerra is approved for use in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate. In the European Union, Arzerra is approved for use in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy. In more than 50 countries worldwide, Arzerra is also indicated as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.
Arzerra is not approved anywhere in the world as treatment for relapsed follicular NHL.

Please see full Prescribing Information, including Boxed WARNING for Arzerra (ofatumumab).

Arzerra is marketed under a collaboration agreement between Genmab and Novartis.

On November 23, 2015 Hanmi Pharmaceutical Co., Ltd. and ZAI Lab Limited reported that they have executed a collaboration and license agreement under which ZAI Lab will acquire exclusive rights in China (including Hong Kong and Macau) to develop, manufacture and commercialize HM61713, a novel, third-generation EGFR targeted therapy for the treatment of EGFR mutation positive lung cancer.

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HM61713 is a novel, third-generation, irreversible EGFR mutant-selective tyrosine kinase inhibitor (TKI) developed to specifically target tumors with T790M mutations. At the ASCO (Free ASCO Whitepaper) Annual Meeting 2015, interim results of the Phase I/II clinical trial were presented and showed strong efficacy signals, combined with a favorable safety profile. In July this year, Hanmi and Boehringer Ingelheim entered into an exclusive license and collaboration agreement for the development and global commercialization rights, except South Korea, China and Hong Kong, of HM61713 (BI1482694).

"We are delighted to partner with Hanmi, a leader in novel drug R&D in Asia and globally," said Samantha Du, Chairman and CEO of ZAI Lab, "NSCLC is a huge unmet need in China with the world’s largest patient population. Our collaboration with Hanmi is aimed at bringing this late stage and potentially revolutionary drug quickly to the Chinese patients. We also look forward to building and continuing our strategic collaboration with Hanmi."

The agreement with ZAI Lab reflects the fact that the population of NSCLC patient in China which HM61713 targets, takes more than a half of total NSCLC patient in the world. According to the Global Data, 46% of the total NSCLC patient in the world this year is in China and by 2020, the Chinese patient population would rapidly increase up to 62% of the total.

Dr. Gwan Sun Lee, CEO of Hanmi said, "Through our collaboration with ZAI Lab with well-built, experienced R&D capability, the possibility to develop HM61713 as a first-in-class drug in China is now open. We look forward to providing innovative treatment options to Chinese patients suffering from lung cancer."