Threshold Pharmaceuticals has disclosed clinical trial results related to its clinical stage hypoxia-activated prodrug, TH-302. The results were presented at the 15th Annual Connective Tissue Oncology Society (CTOS) Meeting in Miami Beach, Florida.
The company said that the 403 trial, which is investigating TH-302 in combination with doxorubicin in patients with soft tissue sarcoma who have not received prior doxorubicin. Twelve patients have had at least one evaluable post-treatment tumor assessment, including 3 (25%) with a partial response (PR) as measured by RECIST (Response Evaluation Criteria In Solid Tumors).
According to Threshold, two of the PRs are confirmed, including one patient who has remained on study for 33 weeks. One of the PRs was unconfirmed due to progression at the subsequent assessment. Five of the 12 patients continue to receive TH-302 after receiving TH-302 for 3 to 13 three-week cycles. Seven (58%) patients achieved stable disease while 2 (17%) had progressive disease. Additional patients are being enrolled to better define the extent of the tumor response activity.
Threshold said that TH-302 continues to be tolerated and there have been no new unexpected adverse events in the 14 patients assessed for safety. Nausea was the most commonly reported adverse event and was reported in 8 (57%) patients. After observing significant, but not dose limiting toxicity at a TH-302 dose of 240mg/m2, prophylactic growth factor support was initiated.
Two dose limiting toxicities, grade 3 cellulitis with grade 4 neutropenia and grade 4 thrombocytopenia, were observed in 2 of 4 patients treated at a TH-302 dose of 340mg/m2. The maximum tolerated dose was then established at 300mg/m2. Skin toxicity is common with 9 of 14 (64%) patients having at least one skin adverse event. All were grade 1 or 2 with the exception of the one patient with grade 3 cellulitis. Eight (57%) patients had a mucosal adverse event; all were grade 1 or 2, the company said.
John Curd, chief medical officer of Threshold, said: “We believe that TH-302 may ‘complement’ doxorubicin, the standard of care in sarcoma, and treat that portion of the tumor that typically does not respond to this traditional chemotherapy agent. This clinical trial has thus far established that TH-302 can be safely combined with full doses of doxorubicin, and the preliminary data suggests that TH-302 may add to the activity and durability of doxorubicin.”