Ziopharm stops enrolment in Phase II sarcoma trial early on positive data
This article was originally published in Scrip
Ziopharm Oncology has stopped enrolment early in a randomised Phase II trial testing its intravenous chemotherapy drug palifosfamide (Zymafos, ZIO-201) in advanced sarcoma on positive interim data. The US company plans to initiate a registration trial, as early as the first half of next year, following regulatory review of the palifosfamide programme to date.
The company's shares rose by 25% to close at $3.60 on Nasdaq on October 14th after the news was announced.
The Phase II PICASSO trial is testing the drug in patients with unresectable or metastatic soft tissue sarcoma in the front- and second-line setting. Patients are randomised either to a standard-of-care treatment in sarcoma, the chemotherapy drug doxorubicin (the only US FDA-approved agent in sarcoma), or to palifosfamide in combination with doxorubicin.
Palifosfamide is DNA alkylating agent which is a stabilised, active metabolite of ifosfamide, another standard of care chemotherapy drug used to treat sarcoma. By using only the active metabolite, and not the toxic metabolites of ifosfamide, its side-effects such as "fuzzy brain" (encephalopathy) and severe bladder inflammation are avoided, the company says. It also claims that palifosfamide is expected to overcome resistance seen with ifosfamide.
The decision to stop enrolment early in the Phase II trial was based on reaching a key efficacy milestone and following safety and efficacy data review by the trial's data committee, sarcoma experts, and the company’s medical advisory board.
A total of 58 of 62 patients treated so far have been evaluated for PFS (progression-free survival; the primary endpoint). In a three-month median follow-up period, 13 patients in the control arm had disease progression versus 6 in the experimental arm, with a hazard ratio of 0.67 representing a 33% reduced risk of progression with palifosfamide during this period of time. The two-sided p-value was 0.04; the pre-defined milestone was to reach one-sided p-value of 0.1. The trial had initially planned to enroll 100 patients.
The interim safety data indicate that the addition of palifosfamide does not add to the toxicity of single agent doxorubicin, the company said. The most frequently reported side-effects in both arms of the study include neutropenia and fatigue, hypokalaemia, nausea, anaemia, leucopenia, and alopecia. The company will report the interim data in full at the upcoming Connective Tissue Oncology Society (CTOS) meeting on November 5th.
"The hypothesis of the randomised Phase II trial design for this very difficult-to-treat cancer population has been validated and the interim results are promising and supportive of a pivotal trial," said Robert Maki, co-leader of the adult sarcoma program at Memorial Sloan-Kettering Cancer Center, and current president of CTOS, a multidisciplinary sarcoma specialty group.