Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
`Vol 22, No 14S (July 15 Supplement), 2004: 2572
`© 2004 American Society of Clinical Oncology
`
`Abstract
`A phase 1 trial of PT-100 in patients receiving
`myelosuppressive chemotherapy
`J. J. Nemunaitis, C. C. Cunningham, N. N. Senzer, E. Haltom, B. Jones, S. J. Vukelja,
`D. A. Richards and M. J. Uprichard
`
`US Oncology, Dallas, TX; Point Therapeutics, Boston, MA; US Oncology, Tyler, TX
`
`2572
`
`Background: PT-100 is a small molecule which competitively inhibits dipeptidyl peptidase
`activity of fibroblast activation protein (FAP) and dipeptidyl peptidase IV (DPP-IV). It rapidly
`increases cytokine (G-CSF, IL-8) production, accelerates neutrophil and erythrocyte
`regeneration, and causes tumor regression in mice via inhibition of FAP and DPP-IV. This
`dose-escalation study was conducted to evaluate the safety of PT-100 in patients receiving
`myelosuppressive chemotherapy (a doxorubicin or taxane based regimen) and to assess
`its effects on neutrophil recovery. Methods: Patients received 2 cycles of chemotherapy:
`the first cycle (C1) served as each patient's individual control. PT-100 was administered
`orally for 7 days in cycle 2 (C2) as a 200, 400, 800, and 1200mcg total daily dose (divided
`twice daily) to 6, 6, 13, and 4 patients, respectively. Most patients received PT-100 on Days
`2–8 of chemotherapy in C2, except at 800mcg where one cohort was treated on a Day 5
`–11 schedule. Patients had to have Grade 3/4 neutropenia in C1 to receive PT-100 in C2.
`Results: Five of 13 patients receiving PT-100 800mcg experienced a
` 2-day improvement
`in
` Grade 3 neutropenia, and a 62% improvement in median AUC in C2 vs. C1 was
`observed in patients treated on the Day 2–8 schedule. A corresponding upregulation in
`G-CSF, IL-6, and IL-8 was observed in most patients. Overall, PT-100 was well-tolerated.
`Edema/peripheral swelling, hypotension, and hypovolemia were the most common non-
`hematologic AEs considered related to PT-100. Two Grade 3 AEs were considered related
`to PT-100: syncope (1200mcg) and orthostatic hypotension (800mcg). An MTD was not
`reached. Conclusions: Given the accelerated neutrophil recovery, strong preclinical
`evidence of antitumor activity, and tolerable toxicities of PT-100, studies using a longer PT-
`100 dosing schedule are warranted to investigate its antitumor and neutrostatic effects.
`
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`Author Disclosure
`Employment
`or
`Leadership
`
`Consultant
`or Advisory
`
`Stock
`Ownership Honoraria
`
`Research Expert
`
`Funding
`Testimony
`
`Other
`Remuneration
`
`Point
`Therapeutics
`
`Point
`Therapeutics
`
`Point
`Therapeutics
`
`Cell Genesys;
`ONYX
`Pharmaceuticals
`
`Corixa
`
`Abstract presentation from the 2004 ASCO Annual Meeting
`
`(cid:3097)
`
`(cid:3098)
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