High Complete Responses Seen With CPX-351 in AML

Gail Roboz, MD, director of the Leukemia Program at the Weill Medical College of Cornell University and the NewYork-Presbyterian Hospital

Gail Roboz, MD

CPX-351 demonstrated a complete response (CR) or CR with incomplete hematologic recovery (CRi) rate of 47.7% in elderly patients with untreated secondary acute myeloid leukemia (AML), according to early results from a phase III study announced by the drug's developer, Celator Pharmaceuticals.

The analysis of the study was conducted following an induction treatment period. In the comparator arm, patients received conventional 7+3 cytarabine/daunorubicin, which demonstrated a CR/CRi of 33.3%. The relative improvement in response with CPX-351 compared with 7+3 was 43.2%. Overall survival (OS) data from the study are expected to mature in early 2016.

"The magnitude of the CR+CRi rate increase is promising and we may be one step closer to having a superior treatment option for patients with this devastating disease," Gail Roboz, MD, director of the Leukemia Program at the Weill Medical College of Cornell University and the NewYork-Presbyterian Hospital, said in a statement. "The improvement in response rate portends well for a clinically meaningful survival benefit."

In the phase III open-label study, 309 untreated patients with secondary AML were randomized in a 1:1 ratio to CPX-351 or 7+3. All patients in the study were between the ages of 60 and 75 years.

CPX-351, which is a liposomal formulation of cytarabine and daunorubicin, was administered at 100 u/m²IV on days 1, 3, and 5. The infusion time for the liposome injection was approximately 90 minutes. Patients in the 7+3 arm received 100 mg/m²of daily cytarabine through continuous infusion for 7 days and 60 mg/m²of daunorubicin on days 1, 2, and 3.

"We are very pleased with the induction response rate results. This is one of the largest trials conducted in this specific patient population, and based on the improvement seen with CPX-351, we are optimistic about the opportunity for CPX-351 to improve overall survival in this patient population," Scott Jackson, chief executive officer of Celator, said in a statement.

"We look forward to the continued follow up of these patients. If approved, CPX-351 will be well-positioned to become the standard of care for high-risk AML patients.  Further, we believe that significant opportunities exist for the additional development of CPX-351 as the backbone of treatment for AML and other blood cancers."

The Leukemia & Lymphoma Society (LLS) has partnered with Celator in the development of CPX-351. Based on the promising response findings, the organization made an additional payment of $400,000 to Celator, which was not scheduled until the final OS analysis. In total, LLS has granted $4.9 million in funding for the phase III study.

"We continue to be very pleased with the progress and positive outcomes Celator has achieved with the development of CPX-351. We felt it appropriate to accelerate our payments to assist Celator in completing the activities necessary to file the new drug application with the FDA as soon as possible once the overall survival data become available," Louis DeGennaro, PhD, chief executive officer of LLS, said in a statement. "We are optimistic for a successful outcome of the phase III study and want to help accelerate the availability of promising therapies such as CPX-351 to these patients who are in dire need of improved outcomes."

If the OS data are positive, Celator plans to submit a new drug application to the FDA for CPX-351. In two preceding phase II studies, OS was significantly improved with CPX-351 versus 7+3 or standard salvage chemotherapy in the frontline and relapsed setting for patients with AML. Based on this benefit, in January 2015 the FDA granted fast track designation to CPX-351 for the treatment of elderly patients with secondary AML.