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FDA Actions & Updates

The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Monday, September 12, 2016

The FDA notified Lyudmila Bazhenova, MD, at the UC San Diego Moores Cancer Center that the phase I/II study of nivolumab in combination with plinabulin for patients with metastatic non-small cell lung cancer (NSCLC) may proceed with enrolling patients. This follows Bazhenova's submission of an investigator-sponsored Investigational New Drug Application on May 23, 2016.

The study objectives are to define the maximum tolerated dose and/or recommended phase II dose of plinabulin in combination with nivolumab for patients with metastatic NSCLC.

The small molecule immuno-oncology agent, plinabulin, activates dendritic cell maturation, induces tumor antigen specific T-cell activation and down-regulates Treg. Nivolumab is a programmed

cell-death-1 inhibitor that has activity in NSCLC, compared to standard of care.

"The granting of this clearance to begin enrolling patients is an exciting next step for the development of plinabulin," said Bazhenova. "We anticipate that the combination study may lead to additional synergistic efficacy with nivolumab and a well-tolerated safety profile."


Monday, September 12, 2016

The FDA has granted breakthrough therapy designation to LEE011 (ribociclib), in combination with letrozole, for the treatment of hormone receptor positive, human epidermal growth factor receptor

2-negative (HR+/HER2-) advanced or metastatic breast cancer. LEE011 is a selective cyclin-dependent kinase (CDK4/6) inhibitor.

The breakthrough therapy designation is based primarily on positive results of the phase III MONALEESA-2 trial of LEE011 in combination with letrozole in postmenopausal women who had received no prior therapy for their advanced disease. The MONALEESA-2 trial met the primary endpoint of clinically meaningful improvement in progression free survival at a pre-planned interim analysis.

Up to one-third of patients with early stage breast cancer will subsequently develop metastatic disease. The 5-year relative survival rate for stage 3 breast cancer is approximately 72 percent, while metastatic (stage 4) breast cancer has a 5-year relative survival rate of approximately 22 percent.


Monday, September 12, 2016

The FDA approved Sustol (granisetron) extended-release injection. It is a serotonin-3 (5-HT3) receptor antagonist indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide combination chemotherapy regimens.

Sustol utilizes a polymer-based drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days, covering both the acute and delayed phases of chemotherapy-induced nausea and vomiting (CINV).

"Despite advances in the management of CINV, up to half of patients receiving chemotherapy can still experience CINV, with delayed CINV being particularly challenging to control," commented Ralph V. Boccia, MD, FACP, Medical Director, Center for Cancer and Blood Disorders in Maryland. "In our experience, other 5-HT3 receptor antagonists, including palonosetron, are generally effective for 48 hours or less. Sustol, due to its extended-release profile, represents a novel option that can protect patients from CINV for a full 5 days."

The Sustol global phase III development program was comprised of two, large, guideline-based clinical trials that evaluated treatment's efficacy and safety in more than 2,000 patients with cancer. The efficacy in preventing nausea and vomiting was evaluated in both the acute phase (day 1 following chemotherapy) and the delayed phase (days 2-5 following chemotherapy).


Monday, September 12, 2016

Orphan Drug Designation has been given by the FDA for chimeric antigen receptor engineered T cells directed against the target protein CD4 (CD4CAR) for the treatment of peripheral T-cell lymphoma (PTCL).

Although there are clinical development programs ongoing with CAR T cells for CD19+ cell hematological malignancies, CD4+ peripheral T-cell lymphomas (PTCLs) have not been targeted by a CAR therapy in a human trial. PTCLs account for 10-15 percent of all non-Hodgkin lymphomas (NHLs) and are more difficult to treat in comparison to B-cell NHLs.

Furthermore, and with few exceptions, T-cell NHLs have poorer outcomes, lower response rates, shorter times to progression, and shorter median survival in comparison to B-cell NHLs. As a result, the standard of care for PTCLs is not well-established, and the only potential curative regimen is bone marrow transplant (BMT).

However, not only is BMT poorly tolerated, but it is not an option for a significant subset of patients with resistant disease. This leaves many patients with no curative options.

CD4CAR is in development for CD4+ T-cell malignancies. The novel CD4-specific chimeric antigen receptor engineered T cells are properly-matched allogeneic human T cells engineered to express an anti-CD4 scFV antibody domain. An initial phase I clinical study is being planned through collaboration between iCell Gene Therapeutics, the NIH, Indiana Clinical and Translational Sciences Institute, Stony Brook University Hospital, and the Division of Blood and Bone Marrow Transplantation and the Clinical Trial Research Unit at James Graham Brown Cancer Center at University of Louisville.


Monday, September 12, 2016

The FDA awarded an orphan grant to evaluate ONC201, a selective antagonist of DRD2 that belongs to the superfamily of G protein-coupled receptors, in a multiple myeloma clinical trial. The award totals $1.7 million in funding to support a phase II program with ONC201 in relapsed/refractory multiple myeloma.

ONC201 has shown anti-cancer activity in several challenging preclinical models of refractory multiple myeloma. In clinical trials, ONC201 has exhibited exceptional safety, a therapeutic pharmacokinetic profile, induction of pharmacodynamic markers, and early efficacy signals in a number of different cancer types, including non-Hodgkin Lymphoma.

As previously reported in companion research articles published in Science Signaling, ONC201 uses unique triggers to activate the integrated stress response (ISR), which upregulates a host of proteins that induce tumor cell death and inhibit the synthesis of proteins that are key for cancer growth. Multiple myeloma cells are particularly sensitive to ISR activation, which is also a key mechanism of action of proteasome inhibitors that are approved for the treatment of multiple myeloma.

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Sarah DiGiulio
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