Daiichi Sankyo and Plexxikon Suspend Phase III Trial of Drug for Rare Tendon Cancer
October 19, 2016
(Last Updated: October 20, 2016 @ 10:30am PT)
By Mark Terry, BioSpace.com Breaking News Staff
Daiichi Sankyo, headquartered in Tokyo, Japan, and Berkeley, California-based Plexxikon, recently suspended recruitment of people in its Phase III ENLIVEN clinical trial in patients with a giant cell tumor of the tendon sheath.
The last information about the trial was announced on July 29, when the two companies published results from the trial in the New England Journal of Medicine. PLX3397 is an oral targeted CSF-1R inhibitor. Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive cancer of the joint or tendon sheath.
The trial data at that time showed the drug caused prolonged tumor regressions in most patients. “TGCT can be a very difficult disease to manage, with treatment options largely limited to surgery to remove as much of the tumor as possible,” said William Tap, lead author of the study and chief of the Sarcoma Medical Oncology Service at Memorial Sloan Kettering Cancer Center, in a July statement. “Despite the best surgical intervention, recurrence of diffuse TGCT is high and the disease may advance to the point where surgery is no longer an option. These preliminary results demonstrate that by targeting CSF-1R, PLX3397 may inhibit tumor growth in some patients with TGCT, potentially offering those patients an alternative non-surgical treatment option.”
The Phase III ENLIVEN study was developed to evaluate PLX3397 (pexidartinib) in TGCT compared to a placebo. The drug was granted breakthrough status by the U.S. Food and Drug Administration (FDA), and is also being evaluated in glioblastoma, melanoma, ovarian and breast cancers.
Breakthrough Therapy Designation was developed to expedite the development and review of drugs that may show significant benefit over current treatments for serious diseases. At this time there is no FDA-approved systemic treatment for TGCT.
“Surgery is the primary treatment for TGCT, but for patients with a diffuse form of the condition, the tumor is more difficult to remove and has a high rate of recurrence, resulting in multiple complicated surgeries and even amputation in some patients,” said Mahmoud Ghazzi, Daiichi Sanyko’s executive vice president and global head of development, in an October 2015 statement. “We are pleased that the FDA recognizes the unmet need for the treatment of TGCT and we look forward to working closely with the Agency on the expedited development of this potential non-surgical treatment for patients with TGCT.”
In an update, Daiichi Sankyo contacted BioSpace to provide an update to the original trial information. The company indicated that there were cases of non-fatal liver toxicity, which after some changes in the trial protocol, will continue.
“Following review of two (2) recently reported cases of non-fatal, serious liver toxicity, the ENLIVEN data monitoring committee (DMC) recommended that enrollment into the study be suspended. At the time of the suspension 121 patients had been randomized, just five (5) short of the 126 planned. The DMC also recommended measures to address these safety concerns while maintaining the blinded nature of the study. As a result, ENLIVEN will continue to completion in order to evaluate its efficacy and safety endpoints. These measures were reviewed and agreed on by the U.S. Food and Drug Administration, and all regulatory authorities involved in the ENLIVEN study have been notified.”
Patients already enrolled in ENLIVEN will be informed on the update, and if they wish to continue, will need to confirm consent for participation.
Plexxikon also has a clinical trial ongoing with Merck . The two companies are collaborating on an evaluation of PLX3397 and Merck’s anti-PD-1 drug, Keytruda (pembrolizumab). The combination is believed to have the potential for a “double blockade of cancer-induced immune suppression.”
The Phase I/II trial is looking at patients with advanced melanoma and multiple other solid tumors.
“We are excited to evaluate PLX3397 in combination with Keytruda, as each agent is designed to attack cancer cells in different ways,” said Gideon Bollag, Plexxikon’s chief executive officer, in a statement. “Cancer cells use multiple tactics to evade host immune responses, and the combination of these two agents is being investigated to re-activate anti-tumor immunity using distinct and complementary mechanisms. Importantly, both PLX3397 and Keytruda have potential application in multiple types of cancer.”
Plexxikon was acquired by the Daiichi Sankyo Group in April 2011.