Re: Farmas USA
Encouraging Initial Data From Ongoing Phase 1/2 Trial of TH-302 Plus Bortezomib (Velcade(R)) Plus Dexamethasone ("TBorD") in Patients With Relapsed/Refractory Multiple Myeloma Presented at ASH Annual Meeting
SAN FRANCISCO, CA -- (Marketwired) -- 12/06/14 -- Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) today announced new preliminary data from the Phase 2 component of an ongoing Company-sponsored Phase 1/2 trial of TH-302, the Company's lead investigational anticancer drug, in combination with the proteasome inhibitor bortezomib (Velcade®) and low-dose dexamethasone ("TBorD") for the treatment of patients with relapsed/refractory multiple myeloma (MM). The median number of prior therapies was 8 (range, 4-12). The recommended phase 2 dose of TH-302 was determined to be 340 mg/m2 and no dose limiting toxicities were observed at this dose level. Partial responses (one very good partial response and one partial response) were observed in 2 of 7 (29%) evaluable patients overall and 2 of 4 (50%) evaluable patients at the recommended phase 2 dose of TH-302. These data are being presented today at the 56th ASH Annual Meeting and Exposition in San Francisco, California (Abstract #2142).
"These initial responses to TBorD therapy are encouraging given that these patients had progressive disease despite having received multiple types of treatment prior to enrollment in this study," said Irene Ghobrial, M.D., Medical Oncologist at Dana-Farber/Brigham and Women's Cancer Center and Principal Investigator of the Phase 1/2 trial. "I am also pleased with the initial safety and tolerability assessments of the TBorD regimen. In collaboration with the Blood Cancer Research Partnership, we are continuing to accrue patients to the study. Potential new treatment options for patients who have developed resistance to currently available therapies would be an important and welcome advancement in the multiple myeloma community."
"TH-302 is currently the subject of multiple clinical trials in various solid tumors, including a pivotal phase 3 trial in patients with advanced soft tissue sarcoma and another pivotal phase 3 trial in patients with advanced pancreatic cancer," said Barry Selick, Ph.D., Chief Executive Officer of Threshold. "We are pleased to see that these early clinical data in relapsed/refractory multiple myeloma are consistent with preclinical models of multiple myeloma, which demonstrated synergistic activity of combination therapy with TH-302 and bortezomib in vitro. The clinical data continue to provide support for further investigation of TH-302 in hematological malignancies, such as multiple myeloma, where hypoxia is believed to play a key role in treatment resistance."
About the Phase 1/2 Trial
The ongoing Phase 1/2 trial is investigating TH-302 and dexamethasone with or without bortezomib with respect to safety and tolerability, dose-limiting toxicities and the maximum-tolerated dose of TH-302, and preliminary efficacy in patients with relapsed/refractory MM.
A total of 18 patients with relapsed/refractory MM have been enrolled in the Phase 2 TBorD component of the study as of November 17, 2014. For the ASH presentation, preliminary safety and efficacy analyses are being presented from 9 patients (7 of whom were evaluable) who initiated therapy prior to September 12, 2014, with presented analyses reflecting data in the clinical database as of November 25, 2014.
Key data from TBorD dosing cohorts being presented at ASH include:
Preliminary assessment of safety and tolerability
No dose limiting toxicities were reported during Cycle 1 at TH-302 doses of 240 mg/m² or 340 mg/m². The maximum tolerated dose of TH-302 with dexamethasone had previously been established at 340 mg/m2, and dose escalation above that dose of TH-302 with dexamethasone plus bortezomib was not allowed.1 Therefore, after 6 patients had been treated at 340 mg/m2 without a dose limiting toxicity, the recommended Phase 2 dose of TH-302 in TBorD was established at 340 mg/m2.
Safety data were available for 8 of 9 patients. The most common Grade 3/4 hematological adverse events were thrombocytopenia (reported in 4 patients), anemia (reported in 2 patients), and lymphopenia (reported in 2 patients). Fatigue (reported in 5 patients; one Grade 3/4) and nausea (reported in 4 patients; one Grade 3/4) were the most common non-hematological adverse events. Five serious adverse events (SAEs) were reported in 4 patients. One SAE of thrombocytopenia was considered related to TH-302. Skin toxicity, an adverse event of interest with TH-302, was limited: a Grade 2 rash resulting in treatment delay was reported at the 240 mg/m2 dose of TH-302, and one Grade 2 skin lesion with no impact on treatment was reported at the 340 mg/m2 dose of TH-302. There were no deaths related to the study drug.
Preliminary assessment of clinical activity
Of the 9 patients included in the ASH presentation, 7 were evaluable for response. According to modified International Myeloma Working Group (IMWG) criteria,2,3 responses included one very good partial response (VGPR), one partial response (PR), and 4 stable disease (SD) assessments; one patient had progressive disease (PD). The patients with PR and VGPR had both previously undergone two autologous transplantations and had received prior current standard treatment including IMiDs, proteasome inhibitors, dexamethasone, and at least one conventional alkylating agent.
