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TH-302 demonstrates encouraging activity in soft tissue sarcoma
The investigational hypoxia-targeted drug TH-302 was associated with PFS, OS and tumor response rates that compared favorably with other first-line agents for soft tissue sarcoma, according to results of a phase 2 study.
The analysis included 91 patients with advanced disease.
Patients received 300 mg/m2 TH-302 (Threshold Pharmaceuticals) — a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard — in combination with 75 mg/m2 doxorubicin. TH-302 was administered on days 1 and 8 of each 21-day cycle, whereas doxorubicin was administered on day 1 of each cycle.
After six cycles, those who achieved stable disease or demonstrated responding disease switched to TH-302 maintenance therapy.
Researchers reported a 6-month PFS rate of 58% (95% CI, 46-68). Historical 6-month PFS rates associated with first-line chemotherapy have ranged from 30% to 56% depending on histologic subtype, researchers wrote.
Researchers observed a complete response rate of 2% and a partial response rate of 34%. Median PFS was 6.5 months (95% CI, 5.8-7.7) and median OS was 21.5 months (95% CI, 16-26.2).
Of the 48 patients who underwent TH-302 maintenance therapy, five improved from stable disease to partial response, and one patient improved from partial response to complete response.
Fatigue, nausea and skin and/or mucosal toxicities, anemia, thrombocytopenia and neutropenia were the most common adverse events observed during induction therapy. Those events were less frequent and less severe during the maintenance phase.
“There is an unmet need for a therapeutic agent that can increase the efficacy of first-line doxorubicin treatment of advanced soft tissue sarcoma without adding unacceptable toxicity,” the researchers wrote. “Our preliminary efficacy and safety data with a TH-302 hypoxia-targeting strategy in this phase 2 study supported the initiation of a randomized, controlled phase 3 study of doxorubicin and TH-302 in soft tissue sarcoma.”
Disclosure: The researchers report employment/leadership positions with, consultant/advisory roles with, stock ownership in and honoraria/research funding from Amgen, Berg Pharma, EMD Serono, GlaxoSmithKline and Threshold Pharmaceuticals.