CytRx said its lead product candidate aldoxorubicin missed its primary endpoint in a Phase III trial comparing the cancer treatment candidate to investigator’s choice of therapy in patients with relapsed or refractory soft tissue sarcomas (STS).
Aldoxorubicin treatment was followed by 4.17 months of progression-free survival (PFS) at month 24—a statistically insignificant difference from the 4.04 months of PFS from investigator's choice of therapy, CytRx acknowledged yesterday, following an analysis of trial results that followed 191 progression events.
But the company added that the analysis did not allow for sufficient follow-up for the nearly two-thirds of patients who entered the Phase III study after the lifting of a partial clinical hold in November 2014. As a result of the hold—which was related to a single patient enrolled in a compassionate use study—nearly half of all patients were excluded from the analysis.
CytRx said it expects to conduct a second analysis, including a longer patient follow-up period, with the goal of announcing results and conducting an end-of-Phase III meeting with the FDA in the fourth quarter.
The Phase III trial enrolled 433 patients at 79 sites in 15 countries, including the U.S. and Canada. Patients with metastatic, locally advanced, or unresectable soft tissue sarcomas who had either not responded to, or who had progressed following treatment with one or more systemic regimens of nonadjuvant chemotherapy were randomized for treatment with aldoxorubicin or the investigator's choice of an approved chemotherapeutic regimen—including doxorubicin, ifosfamide, dacarbazine, pazopanib (Votrient®), or gemcitabine plus docetaxel.
The trial was conducted in accordance with a Special Protocol Assessment granted by the FDA.
CytRx trumpeted other results from the Phase III trial, namely a near-doubling of objective response rate (ORR) and disease control rate, defined as ORR plus stable disease for 4 or more months in the aldoxorubicin arm compared to investigator's choice, including in patients who previously received treatment with doxorubicin. Disease control rate for aldoxorubicin was significantly greater than investigator's choice therapy in the intent-to-treat population, as well as in patients who received prior doxorubicin.
“While results from this current analysis are immature, a near doubling of response rates with aldoxorubicin suggests a highly active therapy which may benefit certain patients with soft tissue sarcoma,” Sant Chawla, M.D., F.R.A.C.P., principal investigator and director of the Sarcoma Oncology Center in Santa Monica, CA, said in a statement.
Patients continue to be followed for overall survival, a secondary endpoint of the trial; other secondary endpoints included response rates and safety. The company said it plans to present updated results of the trial “at an upcoming medical meeting.”
Aldoxorubicin is a cytotoxic compound designed to deliver doxorubicin into tumors without the anticancer agent’s key limitations of cumulative dose restrictions and cardiotoxicity. Aldoxorubicin uses a novel acid-sensitive linker that selectively binds to albumin, shuttling the cytotoxic payload directly into the tumor and potentially sparing the surrounding tissue.
Investors responded to CytRx’s news with a stock selloff that sent the company’s share price down nearly 69% in after-hours trading, to 79 cents as of 8:26 a.m. from yesterday’s close of $2.51.