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CheckMate -017, A Phase 3 Study of Opdivo (Nivolumab) Compared to Docetaxel in Patients with Second-Line Squamous Cell Non-small Cell Lung Cancer, Stopped Early

On January 11, 2015 Bristol-Myers Squibb Company reported that an open-label, randomized Phase 3 study evaluating Opdivo versus docetaxel in previously treated patients with advanced, squamous cell non-small cell lung cancer (NSCLC) was stopped early because an assessment conducted by the independent Data Monitoring Committee (DMC) concluded that the study met its endpoint, demonstrating superior overall survival in patients receiving Opdivo compared to the control arm (Press release Bristol-Myers Squibb, JAN 11, 2015, View Source [SID:1234501315]). The company will share these data – which for the first time indicate a survival advantage with an anti-PD1 immune checkpoint inhibitor in lung cancer – with health authorities.

CheckMate -017 investigators are being informed of the decision to stop the comparative portion of the trial. Bristol-Myers Squibb is working to ensure that eligible patients will be informed of the opportunity to continue or start treatment with Opdivo in an open-label extension as part of the company’s commitment to providing patient access to Opdivo, and characterizing long-term survival. The company will complete a full evaluation of the final CheckMate -017 data and work with investigators on the future presentation and publication of the results.

About the Study

CheckMate -017 is a Phase 3, open-label, randomized study of Opdivo versus docetaxel in previously treated patients with advanced or metastatic squamous cell NSCLC. The trial randomized 272 patients to receive either nivolumab 3 mg/kg intravenously every two weeks or docetaxel 75 mg/m2 intravenously every three weeks. The primary endpoint is overall survival. Secondary endpoints include objective response rate and progression free survival.

Chipscreen Biosciences Announces CFDA Approval of Chidamide (Epidaza) for PTCLs in China

On January 9, 2015 Chipscreen Biosciences reported regulatory approval of Chidamide (Epidaza), the world first orally administrated and subtype-selective histone deacetylase (HDAC) inhibitor for relapsed or refractory peripheral T-cell lymphoma (PTCL) patients, in China on Dec. 23, 2014 by the Chinese Food and Drug Administration (CFDA) (Press release, Shenzhen Chipscreen Biosciences, JAN 9, 2015, View Source [SID1234551991]).

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Peripheral T-cell lymphomas (PTCL) is a set of rare and heterogeneous group of mature T- and natural killer (NK)-cell neoplasms associated with poor outcome. PTCL makes up 25 percent to 30 percent of all Non-Hodgkin’s lymphoma (NHL) cases in China, much higher than that seen in Western countries of 10 percent to 15 percent. The subtype distribution of PTCL is also significantly different between China and Western countries, in which extranodal NK/T-cell lymphoma, nasal type (ENKL), a subtype highly aggressive with very poor prognosis, to be the leading subtype in Chinese population.

"Chidamide is the first new molecular entity discovered and developed by Chipscreen scientists in China. The CFDA’s decision to approval the world first orally administrated selective HDACi for PTCLs is an important validation of the drug’s therapeutic potential for this urgent medical need for Chinese PTCLs patients. The orally administrated Chidamide not just will provide affordable innovative treatment for the Chinese patients whom otherwise have no option to obtain most up-to-dated new treatment beyond conventional chemotherapies, but also have great potential, based on its unique epigenetic mechanism of actions and existing knowledge from the field, to be easily combined with other treatment modalities in comprehensive control and management of cancer patients in fight against drug resistance and tumor recurrence," said Xian-Ping LU, Ph.D., Chief Executive Officer and Chief Scientific Officer of Chipscreen Biosciences Ltd.

About Chidamide (Epidaza)

Chidamide is an orally bioavailable, low-nanomolar inhibitor of cancer-associated histone deacetylase (HDAC) enzymes with favorable pharmacology and tolerability profiles relative to existing benzamide and non-benzamide HDAC inhibitors. It targets specifically the subtype 1, 2, 3 of Class I and subtype 10 of Class IIb HDAC and is being studied in multiple clinical trials as a single agent or in combination with chemotherapeutic agents for the treatment of various hematological and solid cancers. In clinically administrated concentrations, it demonstrated a unique epigenetic mechanism of actions against tumor cell development, involving preferential induction of growth arrest and apoptosis in blood and lymphoid-derived tumor cells, activation of NK-mediated and CD8-mediated antigen-specific cellular anti-tumor immunity, differentiation of tumor stem cells, reversal of drug-resisting tumor cells and epithelia to mesenchymal transition, which are hallmarks of treatment resistance, tumor cell metastasis and recurrence.

Information about Chidamide: www.epidaza.com

Incyte and Agenus Announce Global Alliance to Develop Novel Immuno-Oncology Antibodies

On January 9, 2015 Incyte reported a global license, development and commercialization agreement focused on novel immuno-therapeutics using Agenus’ proprietary Retrocyte Display antibody discovery platform (Press release Agenus, JAN 9, 2015, View Source [SID:1234501312]).

The alliance will initially focus on the development of checkpoint modulator antibodies directed against GITR, OX40, LAG-3 and TIM-3. Agenus and Incyte will share all costs and profits for the GITR and OX40 antibody programs on a 50:50 basis, with Agenus eligible for potential milestones; TIM-3 and LAG-3 are royalty-bearing programs to be funded by Incyte, with Agenus eligible for potential milestones and royalties. The first clinical trials are expected to be initiated in 2016.

“This alliance with Agenus adds therapeutic antibody capabilities to our proven small molecule discovery expertise, significantly expands the landscape of potential immuno-oncology targets available to us, and strengthens our ability to identify and advance novel therapeutic combinations,” said Hervé Hoppenot, President and CEO of Incyte.

“Incyte’s track record of success in oncology development and commercialization, together with our therapeutic antibody expertise and the commonality of our objectives, speak to the compelling strategic rationale for this alliance,” said Garo H. Armen, Ph.D., Chairman and CEO of Agenus. “Our Retrocyte Display technology has produced high quality antibody candidates and offers significant advantages over competing technologies. With Incyte, we believe we have an ideal partner to help define the evolving treatment paradigm of cancer immunotherapies.”

Under the terms of the agreements between the parties, Incyte will make upfront payments to Agenus totaling $25 million and invest $35 million by purchasing approximately 7.76 million newly issued shares of Agenus common stock at a price of $4.51 per share. In addition to the initial four target programs in the alliance, the parties have an option to jointly nominate and pursue additional targets within the framework of the multi-year collaboration. Terms also include:

For each royalty-bearing product, Agenus will be eligible to receive up to $155 million in future contingent development, regulatory and commercialization milestones.
Also for royalty-bearing products, Agenus will be eligible to receive tiered royalties on global net sales ranging from mid-single to low-double digit rates, and has reserved the right to elect to co-fund 30% of development costs for increased royalties.
For products from any additional programs that the parties elect to bring into the collaboration, Agenus may opt to designate them as profit-share products.
For each profit-share product, Agenus will be eligible to receive up to $20 million in future contingent development milestones.

Retrocyte Display is a proprietary retroviral technology that enables a highly diverse library (>1×109) of human IgG molecules to be displayed on the surface of B-lineage cells. This innovative cell-displayed expression platform permits the rapid generation of fully human and humanized therapeutic antibodies with high affinity and target specificity.

The closing of the transaction is conditioned on the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.

AVEO Receives Confirmation of Eligibility for Submission of a Tivozanib Marketing Authorization Application to the European Medicines Agency

On January 8, 2015 AVEO Oncology reported that it has received written confirmation from the European Medicine Agency (EMA) that tivozanib is eligible for submission of an application for a European Union Marketing Authorization under the Agency’s centralized procedure (Press release AVEO, JAN 8, 2015, View Source;p=RssLanding&cat=news&id=2004942 [SID:1234501284]). Confirmation of eligibility was given in response to the submission of a letter of intent enabling the Company to evaluate the opportunity for submitting a Marketing Authorization Application (MAA) for tivozanib with the EMA for the treatment of renal cell carcinoma (RCC). Tivozanib is an oral, potent, selective inhibitor of vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) with a long half-life and activity against all three VEGF receptors. Tivozanib has previously been granted orphan drug designation in Europe for the treatment of RCC.

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The letter of intent, which must be filed at least seven months prior to submission of a MAA, initiates the process to address a number of pre-submission requirements, including the assignment of a Rapporteur and Co-Rapporteur, who are two appointed members of the Committee for Human Medicinal Products (CHMP). The CHMP is the committee responsible for preparing opinions on questions concerning human medicines. Confirmation of eligibility for submission is not predictive of the EMA’s approval of a MAA.

"Our letter of intent and the subsequent confirmation of eligibility by the EMA are first steps in evaluating the potential for submission of a tivozanib MAA in Europe for the treatment of RCC," said Michael Bailey, president and chief executive officer of AVEO. "AVEO and its global RCC clinical advisors continue to believe that tivozanib has the potential to offer RCC patients an alternative to existing therapies. With the European rights to tivozanib recently regained, we now have the opportunity to work with the EMA to fully evaluate the potential for a MAA submission."

AVEO remains encouraged by the clinical outcomes from its Phase 2 and Phase 3 studies in RCC and the efficacy and tolerability profile that tivozanib may offer to patients suffering from this challenging disease. AVEO recently entered into an option agreement with Ophthotech to investigate tivozanib for the potential treatment of non-oncologic diseases of the eye, and the Company is actively pursuing partnerships to advance the development of tivozanib in solid tumors.

Pfizer Provides Update on IBRANCE® (palbociclib)

On January 8, 2015 Pfizer reported that The U.S. Food and Drug Administration (FDA) has informed Pfizer that at this time there is no plan for an Oncologic Drugs Advisory Committee meeting for IBRANCE (palbociclib) (Press release Pfizer, JAN 8, 2015, View Source [SID:1234501294]). Pfizer continues to have an open and productive dialogue with the FDA as the application for IBRANCE advances. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is April 13, 2015. The Company reports that it has entered label discussions with the FDA and hopes to be able to bring IBRANCE to patients who need it as soon as possible.