A phase 2 study of tasisulam sodium (LY573636 sodium) as second-line treatment for patients with unresectable or metastatic melanoma

John M. Kirkwood, Rene Gonzalez, Douglas Reintgen, Philip R. Clingan, Robert R. McWilliams, Dinesh P. De Alwis, Annamaria Zimmermann, Michael P. Brown, Robert L. Ilaria, Michael J. Millward

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

BACKGROUND: Tasisulam sodium (hereafter, tasisulam) is a novel anticancer agent that induces apoptosis through the intrinsic pathway and has antiangiogenic activity in preclinical models. Tasisulam demonstrated activity across a broad range of tumors, including melanoma. The primary objective of this phase 2 study was to determine the objective response rate (ORR) in patients who had received 1 previous systemic chemotherapy for unresectable/metastatic melanoma; secondary objectives were to evaluate the clinical response rate (CRR), progression-free survival (PFS), overall survival (OS), duration of response, safety, and pharmacokinetics. METHODS: Tasisulam was administered intravenously on Day 1 of 21-day cycles according to a lean body weight-based dosing algorithm targeting a peak plasma concentration (C max) of 420 μg/mL. RESULTS: In 68 enrolled patients, the median age was 59 years (range, 26-83 years). No patients had a complete response (CR), 8 patients had a partial response (PR), and 24 patients had stable disease (SD); the ORR (CR + PR) was 11.8%, and the CRR (CR + PR + SD) was 47.1%. The median PFS was 2.6 months, and the median OS was 9.6 months. The predominant treatment-related grade 3/4 toxicity was thrombocytopenia (20.6% of patients). Tasisulam exhibited a biexponential disposition with a predicted distribution half-life of 0.3 hours to 2.8 hours and a median terminal elimination half-life of 10 days (consistent with the turnover of albumin), suggesting that tasisulam is very tightly bound to albumin. CONCLUSIONS: Tasisulam administered at a targeted Cmax of 420 μg/mL on Day 1 of 21-day cycles demonstrated activity and tolerable toxicity as second-line treatment in malignant melanoma. These results led to a registration trial in metastatic melanoma. Cancer 2011;. © 2011 American Cancer Society. Tasisulam, a novel antineoplastic agent, was administered intravenously on Day 1 of 21-day cycles according to a lean body weight-based dosing algorithm targeting a peak plasma concentration of 420 μg/mL. Tasisulam demonstrated antitumor activity and tolerable toxicity as second-line treatment in patients with metastatic melanoma.

Original languageEnglish (US)
Pages (from-to)4732-4739
Number of pages8
JournalCancer
Volume117
Issue number20
DOIs
StatePublished - Oct 15 2011

Keywords

  • LY573636
  • chemotherapy
  • melanoma
  • phase 2
  • tasisulam

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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