Plexxikon today announced positive preliminary data from a pivotal Phase 2 clinical trial of PLX4032 (RG7204) in metastatic melanoma, showing significant tumor shrinkage in the majority of patients. These results support previously reported positive data. Data are being presented at the seventh annual International Melanoma Research Congress of the Society for Melanoma Research (SMR) in Sydney, Australia, by Dr. Jeffrey Sosman, Director of the Melanoma Program at the Vanderbilt-Ingram Cancer Center. PLX4032 is a novel, oral drug that targets a key oncogenic driver in melanoma and other cancers.
“For the first time, we have the possibility of offering a true personalized medicine targeted to melanoma patients who may benefit most from the treatment.”
The Phase 2 (BRIM2) trial is a single-arm study of previously treated metastatic melanoma patients with the BRAF V600 mutation. Primary endpoints for this study are best overall response rate assessed by an independent review committee (IRC) using RECIST criteria, and secondary endpoints are best overall response rate assessed by clinical investigators, duration of response, progression-free survival, overall survival and safety. In pivotal studies, independent review committees are used to review and confirm CT scans, including a second follow-up scan and tumor assessments, allowing a patient's response to be characterized as "confirmed."
Results Confirm Robust PLX4032 Activity
The open-label, multi-center study enrolled 132 patients. As of September 27, 2010, data showed a confirmed response rate of 52 percent, including:
-3 confirmed complete responses (CR) (no evidence of disease)
-66 confirmed partial responses (PR) (tumor shrinkage of at least 30 percent)
In addition, 39 patients had stable disease. The median progression-free survival (PFS) was 6.2 months, compared to historical PFS of less than two months. The median duration of response was 6.8 months. Median overall survival has not yet been reached.
The unconfirmed response rate in the Phase 2 study was 68 percent, further indicating these data are consistent with the data previously reported from the Phase 1 extension study.
The most common drug-related adverse events were rash, photosensitivity, hair loss and joint pain. These were predominantly mild or moderate in severity. Twenty-six percent of patients developed cutaneous squamous cell carcinoma, which was typically managed without treatment interruption.
"These remarkable data provide hope for melanoma patients with the BRAF mutation, who are in dire need of new treatment options for this devastating disease. We are working with the FDA and global health authorities to gather the necessary data to make this treatment available as quickly as possible to these patients," said K. Peter Hirth, PhD, CEO of Plexxikon. "Plexxikon's ability to make highly selective kinase inhibitors has been key to achieving this success. We are excited about exploring the use of PLX4032 in other BRAF-mutant cancers, as well as in combinations with other agents, to potentially enhance this targeted drug's therapeutic potential."
"PLX4032 represents a true paradigm shift in the treatment of melanoma and a real breakthrough in melanoma research," said Dr. Jeffrey Sosman, from Vanderbilt, and the principal investigator for the Phase 2 trial. "For the first time, we have the possibility of offering a true personalized medicine targeted to melanoma patients who may benefit most from the treatment."
PLX4032 also is currently being tested in a randomized, controlled Phase 3 (BRIM 3) trial. Enrollment is ongoing in this trial, with approximately 680 previously untreated mutation-positive, metastatic melanoma patients targeted.
Combination trials with PLX4032 are planned, including a trial to begin in the first quarter of 2011 that will combine PLX4032 and an oral, small molecule MEK inhibitor in melanoma patients with the BRAF mutation. In addition, trials in other BRAF mutant cancers are being planned, including for adjuvant melanoma, thyroid and colorectal cancer.
Data Reflect Earlier Results Reported in NEJM
Results from a PLX4032 Phase 1 extension study in mutation-positive melanoma patients were reported in the August 26, 2010 issue of the New England Journal of Medicine, demonstrating an initial response rate of 81 percent. The confirmed response rate, determined by an investigator assessment for this study, was 59 percent.