Phase III Trial Shows CPX-351 Boosts Overall Survival in AML

The study showed a median OS of 9.56 months with CPX-351 versus 5.95 months for cytarabine and daunorubicin (HR, 0.69;P= .005). Celator announced plans to submit a new drug application to the FDA later in 2016, as well as a marketing authorization application with the European Medicines Agency in early 2017. A presentation of the data is expected at the 2016 ASCO Annual Meeting.

“The overall survival advantage seen with CPX-351 compared to 7+3, along with a superior response rate and no increase in serious toxicity indicates that we'll likely have a new standard of care for treating older patients with secondary AML,” principal investigator for the study Jeffrey E. Lancet, MD, senior member and chief of the Leukemia/Myelodysplasia Program at Moffitt Cancer Center, said a statement. “This represents a major step forward for a very difficult-to-treat patient population.”

The randomized, controlled phase III trial consisted of 309 patients across 39 sites throughout both the United States and Canada who were between the ages of 60 and 75. Patients enrolled in the study were split into either an age group consisting of patients between the ages of 60 to 69 or from 70 to 75. Those enrolled were further stratified based on AML type, treatment-related AML, AML with a history of myelodysplastic syndrome (MDS) and prior treatment with or without a hypomethylating agent, AML with a history of chronic myelomonocytic leukemia, and de novo AML with a karyotype characteristic of MDS.

Patients were randomized in a 1:1 ratio to receive either CPX-351 or conventional cytarabine and daunorubicin. Those receiving CPX-351 were given a first induction of 100u/m²on days 1, 3, and 5 by 90-minute infusion. Patients in the control arm received cytarabine 100mg/m²each day by continuous infusion for 7 days, followed by daunorubicin 60mg/m²on days 1, 2, and 3. Second induction for patients enrolled in the CPX-351 arm was 100u/m²on days 1 and 3, while patients receiving conventional cytarabine and daunorubicin were given cytarabine 100mg/m²each day by continuous infusion for 5 days and daunorubicin 60mg/m²on days 1 and 2.

At 12 months, 41.5% of patients enrolled in the CPX-351 arm remained alive versus 27.6% in the cytarabine and daunorubicin arm. At 24 months, 31.1% of patients enrolled in the CPX-351 arm of the study remained alive compared with 12.3% in the cytarabine and daunorubicin arm. In the short term, 60-day all-cause mortality was 13.7% versus 21.2%, for the CPX-351 and control arm, respectively.

There were no significant differences in grade 3 or higher adverse events between CPX-351 and the cytarabine and daunorubicin regimen, according to Celator. Hematologic grade 3 events included infections, febrile neutropenia, and bleeding.

“These findings confirm that VYXEOS provides the first opportunity we've had in decades to extend survival for patients with high-risk AML,” added Gail Roboz, MD, Professor of Medicine and Director of the Leukemia Program at the Weill Medical College of Cornell University and the New York-Presbyterian Hospital in New York, said in a statement. “Also, more patients in remission means more who are eligible for potentially curative therapy.”

References

1. Celator Announces Phase 3 Trial for VYXEOS™ (CPX-351) in Patients with High-Risk Acute Myeloid Leukemia Demonstrates Statistically Significant Improvement in Overall Survival; March 14, 2016. http://ir.celatorpharma.com/releasedetail.cfm?releaseid=960543. Accessed March 15, 2016.