UPDATED: DMC suspends Daiichi’s ‘breakthrough’ PhIII Enliven trial

Japanese pharma Daiichi Sankyo and drug partner Plexxikon have stopped taking on new patients in a late-stage trial of their rare cancer candidate on the advice of the Data Monitoring Committee after safety concerns. 

In a brief update on the ClinicalTrials.gov website, the company said that “This study has suspended participant recruitment,” coming as a result of a “recommendation of Data Monitoring Committee.” Its status is now “suspended.”

According to its history of changes to the trial record, on Sept. 28 the study stopped recruiting, while on Oct. 14 its status was updated to show it had suspended recruiting because of the DMC’s recommendation.

In a statement to FierceBiotech, Daiichi said: “Following review of two recently reported cases of non-fatal, serious liver toxicity, the ENLIVEN data monitoring committee recommended that enrollment into the study be suspended.

“At the time of the suspension 121 patients had been randomized, just five 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.

“All patients currently enrolled in ENLIVEN are in the process of being informed about this updated safety information and will undergo re-consent for continued participation in the study.”

The Phase III Enliven study was designed to test the investigational oral CSF-1R inhibitor pexidartinib (PLX3397) in patients with a tumor of pigmented villonodular synovitis--or giant cell tumor of the tendon sheath--for whom surgical removal of the tumor would cause more harm than good.

The med was being pitted against placebo to assess the percentage of subjects achieving complete or partial response, and the number of patients who achieve a complete response or partial response at week 25.

In July, Daiichi and Plexxikon posted data in the NEJM from an early-stage study of pexidartinib that showed it “induced prolonged tumor regressions in most patients” with tenosynovial giant cell tumor. Median progression-free survival had not then been reached in that study.

Just a year ago, the drug was given the coveted breakthrough tag from the FDA, and is also being tested in other cancers, including glioblastoma, melanoma, ovarian and breast cancers.

It also has a combo trial deal with Merck’s ($MRK) anti-PD-1 therapy Keytruda (pembrolizumab) in advanced melanoma and other multiple solid tumors.