Singapore, 11 March 2015 - A study led by the Genitourinary (GU) oncology team at National Cancer Centre Singapore (NCCS) has revealed conclusive results in reducing toxicities for Asian patients with metastatic renal cell carcinoma (mRCC) or cancer that has spread beyond the kidney.

The seven-year study began in 2007 and the findings revolutionised the standard protocol for patient management in NCCS with an attenuated-dose regimen of sunitinib for patients with mRCC.

The new treatment regimen for sunitinib has been accepted by oncologists in Singapore. For the patients, this would mean an estimated 30 per cent reduction in fees because of the lower dosage. The median overall survival rate (OStotal) was 27.4 as compared to 21.8 months among patients receiving the attenuated dosage.

Sunitinib was introduced as a treatment for mRCC in Singapore since early 2005. The U.S. Food and Drug Administration (FDA) approved dosing of sunitinib is 50mg once daily for four weeks, followed by a two-week break in a six-week treatment cycle (conventional-doseregimen). Subsequent findings from 2005 to 2006 show that high toxicities were observed with the conventional dosing, especially in Asians.

"Many of the patients were experiencing severe side effects of grade 3 or higher with the conventional dosing. Our immediate response was to refine the treatment protocol to improve patients' quality of life", explained Dr Tan Min Han, Visiting Consultant, Division of Medical Oncology and member of the GU team, NCCS.

NCCS initiated a prospective clinical registry with 127 mRCC patients receiving attenuated sunitinib dosing of 37.5mg/d/4/2 (37.5mg of sunitinib once daily for four weeks, followed by a two-2 week break) as treatment protocol in 2007. Clinical data of patients receiving sunitinib at NCCS from 2005 to 2012 and three other tertiary centres in Singapore (Johns Hopkins-International Medical Centre, National University Hospital Singapore, and Onco-Care of Gleneagles Medical Centre) from 2005 to 2009 were used for comparison, representing at least 90 percent of all patients with mRCC treated over the period.

The data revealed favourable results between the attenuated dosing regimen compared to the conventional dosing. 59 percent of the participants experienced severe side effects as compared to the previous 85 percent; 24 percent than 58 percent required reduction in dose delays; and 35 percent rather than 70 percent of patients requiring dose reduction during their course of treatment. Both dose delays and reduction are only required when high level of toxicities are observed.

Dr Tan reiterated the importance of the findings, "This is an affirmation to our efforts and we believed that the continuous understanding of real world outcomes will reap greater benefits for our patients. The findings would not be possible without the collaborative nature of our tertiary healthcare counterparts."

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This research was published in Clinical Genitourinary Cancer journal in November 2014 and supported by a grant of $50,000 from the NCC Research Fund.

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Celldex Therapeutics has entered into a clinical trial collaboration with Roche to evaluate the safety, tolerability and preliminary efficacy of the combination of varlilumab and MPDL3280A (anti-PDL1) in a Phase I/II trial to treat renal cell carcinoma.

As part of the deal, Roche will provide study drug and Celldex will be responsible for conducting and funding the trial, which is scheduled to be initiated later this year.

Varlilumab, Celldex's fully human monoclonal antibody that targets CD27, and MPDL3280A (anti-PDL1), Roche's investigational cancer immunotherapy, are part of a new class of investigational medicines known as cancer immunotherapies.

CD27 is a critical molecule in the activation pathway of lymphocytes and it can be effectively manipulated with activating antibodies to induce potent anti-tumor responses and may result in fewer toxicities due to its restricted expression and regulation.

Celldex Therapeutics executive vice-president and chief medical officer Dr Thomas Davis said: "This collaboration with Roche furthers our ongoing initiative to investigate varlilumab's potential in combination with a broad range of mechanisms and across multiple tumor types.

"Varlilumab is currently being studied in two Phase I/II combination studies and we expect it will enter at least another four combination studies this year."

The immunotherapies are designed to harness the body's own immune system to fight cancer through separate yet complementary mechanisms of action that may allow the activation of T cells, restoring their ability to effectively detect and attack tumor cells.

According to preclinical data, the combination of these two mechanisms is expected to improve anti-tumor immune response compared to either agent alone.

Positive signs of clinical activity in patients with refractory renal cell carcinoma were observed in Celldex's Phase I trial of varlilumab conducted in multiple solid tumors.

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