• Ariela Noy, David T Scadden, Jeannette Lee, Bruce J Dezube, David Aboulafia, Anil Tulpule, Sharon Walmsley, and Parkash Gill.
• Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. noya@mskcc.org
• J. Clin. Oncol. 2005 Feb 10; 23 (5): 990-8.

PurposeIM862 is a synthetic dipeptide (L-glutamine L-tryptophan) with in vitro and in vivo antiangiogenic properties. Phase I/II studies showed minimal toxicity and a response rate of 36% in AIDS-Kaposi's sarcoma. We report a 24-week, randomized, double-blinded, placebo-controlled phase III trial with the phase II dose, 5 mg intranasally every other day.Patients And MethodsTwo hundred two HIV-positive patients were enrolled, 104 on IM862 and 98 on placebo.ResultsBaseline characteristics were comparable except current antiretroviral therapy: 88% versus 96% (IM862 v placebo group; P = .042). The median treatment durations were 19.5 versus 24 weeks (IM862 v placebo). No significant difference was detected in response rate (IM862, 23%; 95% CI, 15% to 32% v placebo, 21%; 95% CI, 14% to 31%; P = .46), time to response (8.5 weeks v 14 weeks; P = .024), or duration of response. However, IM862 was associated with both a shorter time to response (8.5 weeks v 14 weeks; P = .024) and shorter median time to progression (16 weeks, 95% CI, 13 to 27 weeks v 35 weeks, 95% CI, 26 to 114 weeks; P = .012).ConclusionDespite promising phase I and phase II studies, IM862 5 mg every other day was not superior to placebo and may accelerate time to progression. Highly active antiretroviral therapy alone was associated with a substantial rate of sustained tumor response and may have contributed to prior estimates of IM862 response. Therapeutic trials for AIDS-Kaposi's sarcoma must account for ongoing immune reconstitution in the setting of concurrent highly active antiretroviral therapy that may confound estimates of therapeutic activity.

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