The final results of a Phase 1/2 clinical trial indicate that perifosine in combi­nation with Velcade and dexamethasone may be effective in mul­ti­ple myeloma patients who previously relapsed from or were treatment-resistant to Velcade.

The trial results made a favorable impression on Dr. Philip McCarthy of the Roswell Park Cancer Institute in Buffalo, New York, who was not involved in the study.

“This combination had activity with an overall response rate (complete response, near complete response, partial response, and minor re­sponse) of 41 percent which is quite reasonable and exciting in this heavily pre­treated population,” said Dr. McCarthy.

Dr. Paul Richardson from the Dana-Farber Cancer Institute in Boston presented these results at the American Society of Hematology (ASH) annual meeting in December.

Perifosine (KRX-0401) is an orally administered drug being developed by Keryx Biopharmaceuticals (NASDAQ: KERX) and Aeterna Zentaris (NASDAQ: AEZS). It belongs to a new class of anti-cancer drugs known as “Akt-inhibitors.” Akt is a protein believed to play an important role in the development and growth of cancer cells.

According to Dr. McCarthy, perifosine was shown in laboratory studies to have activity against cell lines that were resistant to older anti-myeloma drugs such as melphalan (Alkeran), doxorubicin (Adriamycin), and dexamethasone (Decadron).  He added that when perifosine is combined with anti-myeloma drugs such as Velcade (bortezomib), a synergistic anti-myeloma effect is seen.

“A more than additive anti-cancer effect is seen than with perifosine or Velcade alone,” he explained.

The Phase 1 part of the trial included 18 patients with relapsed/refractory multiple myeloma. For the Phase 2 part, an additional 66 patients were recruited.  Across both phases of the trial, the median patient age was 63 years and the median time between diagnosis and study participation was 4.5 years.

The participants had received a median of five prior lines of therapy.  All patients had previously received Velcade, 98 percent dexamethasone, 76 percent Revlimid (lenalidomide), and 58 percent stem cell transplantation.

Participants received 50 mg of perifosine twice daily and 1.3 mg/m² of Velcade on days 1, 4, 8, and 11 of a 21-day treatment cycle. Patients demonstrating progressive disease could add 20 mg of dexamethasone on the day of and the day after each Velcade dose.

Patients received a median of eight treatment cycles.

Of the 73 patients evaluable for response, 4 percent achieved a complete or near complete response and 18 percent achieved a partial response to treatment.  Another 19 percent achieved a minor response, and 41 percent had stable disease for at least three months,

Of the 20 patients who previously relapsed on Velcade, 10 percent achieved a complete or near complete response and 35 percent achieved a partial response while on the perifosine combination.  Of the 53 patients who were refractory to prior Velcade treatment, 2 percent achieved a complete or near complete response and 11 percent achieved a partial response.

The median progression-free survival time was 6.4 months for all participants. For Velcade-relapsed and Velcade-refractory patients, the median progression-free survival was 8.8 months and 5.7 months, respectively.

For all evaluated patients, the median overall survival was 25 months. This measure was 30.4 months for Velcade-relapsed patients and 22.5 months for Velcade-refractory patients.

Severe side effects included low platelet counts (23 percent of patients), low white blood cell counts (15 percent), anemia (14 percent), pneumonia (12 percent), and muscle and bone pain (11 percent).

Three percent of patients experienced severe, but reversible, peripheral neuropathy, a condition characterized by pain and tingling in the extremities due to nerve damage; 29 percent of patients experienced mild to moderate peripheral neuropathy.

A global Phase 3 clinical trial assessing the perifosine-Velcade-dexamethasone combination in relapsed and refractory patients with prior Velcade treatment is currently underway.

For more information, please see abstract 815 on the ASH annual meeting website or Dr. Richardson’s slide deck, which he has made available as a courtesy to The Beacon’s readers.  For more information on the ongoing Phase 3 trial, please see the clinical trial description.