Phase 1 extension study results of Plexxikon's PLX4032 in metastatic melanoma patients encouraging

www.plexxikon.comSep 23 2009

Plexxikon Inc. today announced encouraging clinical data from a Phase 1 extension study of PLX4032 (RG7204) in metastatic melanoma patients, which expand the results announced from the initial phase of the study. PLX4032 is a novel, oral and highly selective drug that targets the BRAF^V600E cancer-causing mutation that occurs in about 50 percent of melanomas and about eight percent of all solid tumors. Tumor shrinkage has been observed in nearly all of the currently evaluable patients in the extension study, reflecting a 70 percent response rate. These data will be presented at the ECCO 15/ESMO 34 Joint Multidisciplinary Congress in Berlin, Germany. Larger clinical trials to support a registration program for product approval are targeted to start shortly. Plexxikon and Roche are co-developing PLX4032 under their 2006 license and collaboration agreement.

Patients who tested positive for the BRAF^V600E mutation have been enrolled in the open-label, single-arm extension cohort. All patients have been treated with PLX4032 at 960 mg twice daily (BID), with anti-tumor effects measured by RECIST (Response Evaluation Criteria in Solid Tumors) every eight weeks. Patients will be treated until disease progression. Eligible patients for this trial must have progressed after at least one prior treatment. While enrollment for the melanoma extension cohort is complete, Plexxikon is enrolling a second cohort of patients with colorectal cancer and expects enrollment to be complete by year end.

Melanoma Extension Study Confirms Safety & Tumor Regression Seen in Phase 1 Dose Escalation Study

In an extension study of melanoma patients with the BRAF^V600E mutation, 31 patients have been enrolled, most of whom have the worst stage of metastatic disease (Stage M1c), and who were treated with PLX4032 at 960 mg BID. Among the 27 evaluable patients to date, results confirm the preliminary safety and efficacy seen in the previous Phase 1 dose escalation study:

• PLX4032 was well tolerated at 960 mg BID, now confirmed as the maximum tolerated dose
• Complete response in 1 patient treated for 3 cycles
• Partial responses of greater than 30% tumor regression by RECIST criteria have been observed in 18 patients, with 15 patients showing responses of greater than 50%
• Minor responses in 6 patients showed tumor regression between 10% and 30%

Median progression-free survival (PFS) has not been achieved since it is too early in the study to report. However, the earlier reported interim median PFS for the Phase 1 dose escalation study has now increased to seven months as patients continue on treatment.

Drug-related adverse events were predominantly mild in severity and included rash, joint pain, photosensitivity and fatigue. Serious adverse events were observed in some patients after chronic treatment, including seven patients with cutaneous squamous cell carcinoma (keratoacanthoma subtype) that was removed by excision, while treatment with PLX4032 was continued. A risk management plan is in place for baseline evaluation of the skin and monitoring of all patients while on the extension study.

“Since we have now confirmed the earlier Phase 1 results for PLX4032 in metastatic melanoma, we are moving quickly to advance this product candidate to pivotal trials, which we expect to start shortly,” stated K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. “The results we are seeing with PLX4032, our most advanced selective kinase inhibitor, are encouraging in terms of both efficacy and safety. Our precision engineering of new drug candidates could confer a safety advantage compared to other less targeted agents, for cancer patients as well as for those patients suffering from other chronic diseases.”