A Phase 1b/Pharmacokinetic Trial of PTC299, a Novel PostTranscriptional VEGF Inhibitor, for AIDS-Related Kaposi's Sarcoma: AIDS Malignancy Consortium Trial 059

作者：Ignacio Rachel A Bender^*; Lee Jeannette Y; Rudek Michelle A; Dittmer Dirk P; Ambinder Richard F; Krown Susan E

来源：JAIDS: Journal of Acquired Immune Deficiency Syndromes , 2016, 72(1): 52-57.

• Kaposi's sarcoma (KS)
• vascular endothelial growth factor (VEGF)
• vascular endothelial growth factor inhibitor (VEGF inhibitor)
• Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8)
• HIV/AIDS-related malignancy
• pharmacokinetics (PK)

Vascular endothelial growth factor (VEGF) plays an important role in Kaposi's sarcoma (KS). We administered PTC299, a post-transcriptional inhibitor of pathogenic VEGF, to persons with HIV-related KS. Seventeen participants received 3 different doses of PTC299. Adverse events typically observed with VEGF inhibition were absent. Three participants had partial tumor responses and 11 had stable disease. There were no differences in exposure to PTC299 by antiretroviral regimen. Serum VEGF, but not KS-associated herpesvirus DNA, decreased on treatment. Given redundancies in the VEGF feedback loop, future trials should consider combining PTC299 with agents that inhibit different pathways implicated in KS and KS-associated herpesvirus proliferation.

• 出版日期2016-5-1