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    Research at CPMC helps lead to FDA approval of nivolumab for melanoma

    January 2, 2015

    One of the newest classes of agents to treat melanoma and other types of cancer, checkpoint inhibitors, have emerged as promising therapies in slowing and even preventing tumor growth.

    And with the U.S. FDA approval on December 22 of the checkpoint inhibitor nivolumab for the treatment of melanoma, the drugs are expected to bring new hope to the more than 76,000 people in the U.S. diagnosed annually with this deadly form of skin cancer.

    Nivolumab is an immunosuppressive drug that works by releasing a natural immune system ‘brake’ known as PD-1 that some tumors use to evade an immune system attack.

    Studies at California Pacific Medical Center (CPMC)’s Center for Melanoma Research and Treatment were key to FDA approval of the drug, and CPMC entered more patients on this study than did any other cancer center worldwide.

    In the phase 3 open-label trial that led to FDA approval, the objective response rate (ORR) and overall survival (OS) of nivolumab were compared to responses with investigator’s choice of treatment, in subjects with advanced melanoma.

    Key data on the drug were presented at the 2014 ESMO Congress that examined its effects in patients with advanced melanoma who had progressed on or after anti-CTLA-4 therapy or treatment with a BRAF inhibitor. Patients were randomly assigned two-to-one to treatment with nivolumab, or investigator’s choice chemotherapy.

    ORR was assessed in 120 patients assigned nivolumab and 47 assigned chemotherapy with a follow-up of six months. Patients treated with nivolumab had an ORR of 32% compared with 11% for patients assigned chemotherapy. Safety results showed that the most common side effects were rash, itching, upper respiratory tract infections, and edema (swelling).
    Studies have shown that anti-PD1 antibodies show a higher rate of durable responses with less severe toxicity than any other previously approved immunotherapy for melanoma.

    “This research is changing the landscape of cancer therapy, based on these new insights into tumor biology and the molecular pathways underlying metastasis,” said David Minor, M.D., clinician-scientist at CPMC and a scientist at its Research Institute (CPMCRI). “Most investigators feel the ongoing clinical trials of nivolumab in other cancers such as lung, kidney, and ovarian cancer will lead to its use in those diseases also.”

    The research of Dr. Minor and colleague Mohammed Kashani-Sabet, M.D., Director of CPMC’s Center for Melanoma Research and Treatment, and Senior Scientist at CPMCRI, was integral to FDA approval of nivolumab.
    “The drug shows significant promise in saving the lives of patients with late-stage disease who have few options for therapy,” said Dr. Kashani.

    “At CPMC we are committed to building upon our understanding of tumor biology, prognostic indicators, and molecular targets against melanoma.”