During this year’s meeting of the American Society of Hematology (ASH), there were several presentations about tanespimycin, a new drug currently being developed by Bristol-Myers Squibb and Kosan Biosciences. Tanespimycin inhibits Hsp90, which acts as a molecular chaperone for proteins critical to the growth, survival, and drug resistance of cancerous cells.  

Safety And Activity Profile Of Tanespimycin And Velcade From Phase 1/2 Study

One of the ASH presentations showed that the combination treatment of tanespimycin and Velcade (bortezomib) effectively targets Hsp90 in patients with relapsed or refractory multiple myeloma. The treatment is also well tolerated with a low frequency of peripheral neuropathy (nerve damage in the extremities that can cause pain and tingling sensations) and neutropenia (low white blood cell count).

Researchers enrolled 72 patients who had previously been given at least two treatments for myeloma (median = 5 prior treatments). Patients were given intravenous injections of Velcade (in doses of 0.7, 1.0, or 1.3 mg/m²), followed by a one-hour infusion of tanespimycin, on days 1, 4, 8, and 11 of a 21-day cycle.

Forty-eight percent of patients who had never received Velcade treatment responded to the combination regimen, compared to 22 percent of Velcade-pretreated patients and 13 percent of patients who previously had not responded to Velcade treatment. The median duration of response was 12 months.

The safety profile of the combination regimen was also examined during the study. Low platelet counts were observed in 40 percent of patients, with 25 percent of patients experiencing severe complications. Low white blood cell counts were observed in just three percent of patients, and twenty-one percent of patients experienced mild to moderate peripheral neuropathy. These results indicate that the drug combination of tanespimycin and Velcade is very well tolerated in this population of patients.

Safety And Activity Profile Of Tanespimycin And Velcade From Phase 2 Study

Results from another study that were presented at ASH showed that tanespimycin and Velcade had activity in heavily pretreated myeloma patients.

Researchers enrolled 22 patients who had previously been given at least three treatments for myeloma that included both Revlimid (lenalidomide) and Velcade. In addition to receiving 1.3 mg/m² of Velcade, patients were randomized to receive one of three doses of tanespimycin: 50 mg/m², 175 mg/m², or 340 mg/m². The treatments were administered on days 1, 4, 8, and 11 of a 21-day cycle. Patients received, at minimum, four cycles of treatment until progression of disease was observed.

Fourteen percent of the patients responded to treatment in this study, and 45 percent of the remaining patients did not experience disease progression. It is noteworthy that one patient who achieved a partial response had previously received 10 prior treatments, including three Velcade-containing regimens. 

Similar to the results in the phase 1/2 study, the frequency of serious adverse side effects was very low. Thirty-two patients experienced low platelet counts, and 18 percent of patients experienced low white blood cell counts. Twenty-seven percent of patients experienced mild to moderate peripheral neuropathy, with only one patient experiencing severe complications after stopping treatment with tanespimycin. Other common side effects included fatigue (73 percent), nausea (68 percent), diarrhea (64 percent), constipation (50 percent), and vomiting (46 percent).

For more information, see abstracts 2890 (Phase 1/2 Study) and 1871 (Phase 2 Study) at the ASH meeting Web site.