Interim data from an ongoing clinical combination trial of ARRY-520 (Array Biopharma) with carfilozomib (Kyprolis?,Onyx Pharmaceuticals) in patients with relapsed or refractory multiple myeloma (MM) who are refractory or intolerant to bortezomib (Velcade?, Millennium Pharmaceuticals, Inc, a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited) demonstrated early signals of activity with a disease control rate (complete response, partial response, minimal response or stable disease) of 82% and a clinical benefit rate (?minimal response) of 53%, including one complete response.

The trial data shows that the combination of ARRY-520, a highly selective and targeted inhibitor of KSP, with carfilozomib, has been well tolerated and did not result in unexpected hematologic toxicity.ARRY-520 has a novel mechanism of action distinct from currently approved treatment options for MM. The drug candidate preferentially acts on MM cells, versus terminally differentiated or epithelial cells, based on Mcl-1 survival dependence.

The combination of ARRY-520 with carfilozomib has been well tolerated, has a manageable side effect profile and did not result in unexpected hematologic toxicity.

The results further showed a manageable side effect profile.More than half of the patients enrolled remain on study, with patients in the current cohort receiving full doses of both drugs without reaching a maximum tolerated dose (MTD).The current data was presented at the 18th Annual Meeting of the European Hematology Association being held in Stockholm, Sweden June 13 – 16, 2013.

“To date, the combination of ARRY-520 with carfilozomib has been well tolerated. Reversible neutropenia is the most common adverse event and does not appear to be additive relative to the observed events for either drug alone,” said Jatin J. Shah, M.D., Assistant Professor, Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas, MD Anderson Cancer Center. “While this is an ongoing study, and we await mature data, there have been promising signs of activity in a heavily pretreated population, which includes several patients previously exposed to ARRY-520 or carfilzomib.”

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Alpha 1-Acid Glycoprotein
Also at the meeting, updated information was presented on Alpha 1-Acid Glycoprotein (AAG), a potential patient selection marker for clinical activity of ARRY-520 in relapsed and refractory multiple myeloma. The trial results showed that patients with low levels of alpha-1-acid glycoprotein (AAG) had longer event free survival (time to next treatment or death). In a single-agent Phase II ARRY-520 clinical study, the median overall survival was reported to be markedly longer in patients with low AAG as compared to patients with high AAG (20.2 vs. 4.5 months). These results may enable more precise targeting of patient populations who will benefit from ARRY-520.

ARRY-520 is also investigated in other clinical trials, including a Phase II study of the investigated drugsin combination with dexamethasone in patients with MM refractory tolenalidomide(Revlimid?; Celgene Corp), bortezomib anddexamethasone therapy, a dose escalation trial in combination with bortezomibplus dexamethasone in patients with relapsed or refractory MM and an investigator-sponsored dose escalation trial in combination withcarfilzomibin patients with relapsed or refractory MM who are refractory or intolerant to bortezomibtherapy.

Clinical trials
NCT01372540 – Arry-520 + Carfilzomib for Multiple Myeloma (MM)
NCT00821249 – A Study of ARRY-520 in Patients With Relapsed or Refractory Multiple Myeloma
NCT00462358 – A Study of ARRY-520 in Patients With Advanced Cancer
NCT01248923 – A Study of ARRY-520 and Bortezomib Plus Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
NCT00637052 – A Study of ARRY-520 in Patients With Advanced Myeloid Leukemia

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