Phase 2 Data Demonstrate Perifosine + Sorafenib Well Tolerated in Heavily Pretreated Lymphoma

Aeterna Zentaris announced that final Phase 2 data demonstrated that the combination of perifosine and sorafenib was well tolerated by heavily pretreated patients with relapsed/refractory lymphomas. Perifosine is an oral anticancer treatment that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway.

This investigator-driven trial involved 40 patients with relapsed/refractory lymphomas who had failed second or subsequent-line salvage chemotherapy: there were 3 patients with diffuse large B-cell lymphoma, 3 with follicular lymphoma, 1 with Waldenstrom macroglobulinemia, 8 with chronic lymphocytic leukemia (CLL) and 25 with classical Hodgkin lymphoma (HL). The treatment plan included an initial 4 week treatment with perifosine (50mg BID, per os) to assess tolerability and tumor response. Subsequently, patients achieving less than partial response (PR) were given perifosine (50mg BID, per os) combined with sorafenib (400mg BID, per os) until progression of disease (PD) or significant clinical toxicity. Patients achieving at least a PR went off-study and continued with perifosine (50mg BID, per os) alone until PD or clinical toxicity. Based on tumor response to the initial 4 week perifosine therapy, 36 of 40 patients who achieved less than PR were subsequently administered the perifosine/sorafenib combination therapy. Four CLL patients who achieved at least a PR with perifosine alone, went off-study and continued with single-agent therapy.

For the 36 patients treated with combination therapy, 8 (22%) PR, 15 (42%) stable disease (SD) and 13 (36%) PD were observed. Median overall survival (OS) and progression free survival (PFS) for all patients were 16 and 5 months, respectively. For the 25 patients in the HL subgroup also receiving combination therapy, the overall response-rate was 28%, with 7 PR; for HL patients, median OS and PFS were 16 and 5 months respectively, as it was for all patients.

Sorafenib (Nexavar; Bayer and Onyx) is a multikinase inhibitor indicated for the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma.

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