Relapsed/Refractory Patients:

Perifosine (KRX-0401)

What are the key facts about Perifosine?

• Oral anticancer agent that targets the Akt pathway.

• It has been studied in combination with dexamethasone, Revlimid, or Velcade in clinical trials in relapsed and/or refractory disease, with overall response rates of up to 50% seen.

• Side effects appear to be manageable. The most common severe side effects seen when combined with Velcade included low blood cell counts, pneumonia, and muscle/bone pain.

• Being evaluated in a Phase III trial in combination with Velcade-dexamethasone in patients who have relapsed on a prior Velcade treatment regimen.

What is Perifosine?

Perifosine, also known as KRX-0401, is an oral anticancer agent being developed by Keryx Biopharmaceuticals. Perifosine affects tumor cell growth and survival. In particular, it inhibits the Akt pathway, which is involved in the development of many types of cancer.

Perifosine is being evaluated in late-stage clinical trials in multiple myeloma and colorectal cancer, and in early-stage trials in several other tumor types. The Phase III trial in myeloma is being conducted under a Special Protocol Assessment (SPA) with the US Food and Drug Administration (FDA).

What do we know about Perifosine’s activity in myeloma?

Perifosine has been shown to kill myeloma cells in the laboratory and in animal models, including those that are resistant to conventional anti-myeloma drugs. In addition, in the laboratory, perifosine acts synergistically with other agents, including dexamethasone, doxorubicin, melphalan, and Velcade® (bortezomib).

Perifosine has been studied in combination with dexamethasone, Revlimid® (lenalidomide), and Velcade in clinical trials.

• In a Phase I trial facilitated by the Multiple Myeloma Research Consortium (MMRC), perifosine in combination with Revlimid and dexamethasone had manageable side effects and showed promising activity in relapsed or refractory myeloma with an overall response rate of 50% and extended survival.


• Perifosine, alone and in combination with dexamethasone, showed activity against relapsed/refractory myeloma in a Phase II study (n=67), with preliminary results showing an overall response rate of 35%.


• • The combination of perifosine and Velcade, with or without dexamethasone, showed promising activity in a Phase I/II study involving patients with relapsed/refractory myeloma, all of whom had previously received a median of 5 prior lines of therapy, which included Velcade.


• The combination resulted in an overall response rate (partial response or better) of 22% in 73 evaluable patients, including 4% complete or near-complete responses. An additional 19% of patients achieved a minor response and 41% had stable disease for at least 3 months.


• The combination was active in patients (n=20) who had relapsed on Velcade (ie, they responded, then progressed more than 2 months following completion of treatment), with 10% achieving a complete response (CR) or near-CR and 35% a partial response.


• The combination was also active in patients (n=53) who were refractory to Velcade (ie, they progressed on or within 2 months of treatment), with 2% achieving a CR/near-CR and 11% a partial response.


• The median length of time before myeloma progressed (progression-free survival) was 6.4 months for all evaluable patients and overall survival was 25 months.


• Dose adjustments could be made to manage side effects. The most common adverse events included gastrointestinal effects, fatigue, muscle/bone pain, and upper respiratory infection. The most common severe adverse events included low blood cell counts, pneumonia, and muscle/bone pain.

How is Perifosine currently being studied in myeloma?

A Phase III trial of perifosine plus Velcade-dexamethasone is enrolling patients with myeloma who have relapsed on a prior Velcade treatment regimen. Patients must have received at least one but not more than four prior anti-myeloma therapies and can have refractory disease, but must not be refractory to any Velcade-containing regimen.

• The study will involve approximately 450 patients.


• It will evaluate the time it takes for disease to progress while on the three-drug regimen compared with that seen with Velcade-dexamethasone plus placebo.


• Other measures include overall survival, overall response rate, and safety.

To find a clinical trial, call 1-866-603-MMCT (-6628) or click here to go to the MMRF Patient Navigator Program.