RG7204, a BRAF Inhibitor, Demonstrates Promising Results in Metastatic Melanoma

RG7204, a BRAF Inhibitor, Demonstrates Promising Results in Metastatic Melanoma

An oral investigational therapy, RG7204 (also known as PLX4032), results in stable disease or reduced tumor size for 82% of metastatic melanoma patients who have failed prior treatment and who have the BRAF V600E mutation. These findings were recently presented at the Seventh Annual International Melanoma Research Congress of the Society for Melanoma Research in Sydney, Australia.[1]

Melanoma is less common than non-melanoma skin cancer but tends to be much more aggressive. Of the more than one million new diagnoses of skin cancer each year, roughly 62,000 involve melanoma. More than 8,000 people die of melanoma each year in the United States. What makes melanoma so dangerous is that it is more likely than other types of skin cancer to spread (metastasize) to other parts of the body.

In order to provide more individualized and more effective cancer therapy, much research has been focused on determining specific pathways involved in cancer cell growth or survival. The BRAF gene is known to play a part in cell growth, and mutations in BRAF are common in several cancer types. Research has indicated that 40-60% of melanomas carry a BRAF mutation. Roughly 90% of these BRAF mutations involve a specific mutation known as V600E.

RG7204 is an oral investigational targeted therapy that has shown activity as an inhibitor of BRAF with the V600E mutation in preclinical studies. In a recent small study published in The New England Journal of Medicine, 81% of metastatic melanoma patients experienced a complete or partial regression of their disease when treated with RG7204.[2]

In the current Phase II study, known as the BRIM2 study, researchers evaluated RG7024 among 132 metastatic melanoma patients whose disease had the BRAF V600E mutation. The 132 patients evaluated in this part of the study had received treatment and experienced disease progression or recurrence prior to enrolling in this study. Metastatic melanoma patients who have experienced disease progression following treatment have a median overall survival of six to nine months and typically experience progression of their disease in a couple of months.

  • Progression-free survival was 6.2 months.
  • 52% of the patients experienced a reduction in their tumors by at least 30%, and an additional 30% of patients experienced stable disease.
  • At this time follow-up has not been long enough to determine the median overall survival.
  • Side effects were consistent with prior studies:
    • Severe side effects included abnormal liver function in 14% of patients, joint pain in 11% of patient, and gastrointestinal side effects in 10% of patients.
    • Rash, photosensitivity, hair loss, and joint pain were the most common side effects reported.
    • 26% of patients reported Grade 3 cutaneous squamous cell carcinoma (a type of skin cancer), which was removed.

These data are encouraging and confirm some of the earlier-Phase clinical trial data showing safety and efficacy of RG7024 in previously treated advanced melanoma that is positive for the BRAF V600E mutation. A Phase III study is ongoing in advanced melanoma patients who have not had prior treatment and may further validate this promising treatment.


[1] Sosman J, et al. An open-label, multicenter phase 2 study of continuous oral dosing of RG7204 (PLX4032) in previously treated patients with BRAF V600E mutation-positive metastatic melanoma. Presented at the 7th Annual International Melanoma Research Congress of the Society for Melanoma Research in Sydney, Australia*.* November 4-7, 2010. [Abstract ].

[2] Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of Mutated, Activated BRAF in Metastatic Melanoma. The New England Journal of Medicine. 2010;363:809-819.

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