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Sub-category:
Phase I Studies
Category:
Developmental Therapeutics: Cytotoxic Chemotherapy
Meeting:
2008 ASCO Annual Meeting
Session Type and Session Title:
Poster Discussion, Developmental Therapeutics: Cytotoxic Chemotherapy
Abstract No:
2528
Citation:
J Clin Oncol 26: 2008 (May 20 suppl; abstr 2528)
Author(s):
B. Y. Wong, G. I. Shapiro, M. S. Gordon, M. J. Borad, J. P. Eder, R. Tibes, D. S. Mendelson, E. Wasserman, T. Kawabe, S. Sharma
Abstract:
Background: Most cancer cells are dependent on the G2 checkpoint to survive with DNA damage. The stable peptide CBP501 shows selective G2 checkpoint abrogation, with activity in various tumor models, alone and combined with DNA damaging agents. CBP501 was evaluated in 2 phase I studies, single agent and with CDDP, determining maximum tolerated dose (MTD), dose limiting toxicity (DLT), safety and PK. Methods: CBP501 was given over 1 hr, via central catheter, with prophylactic anti-allergics due to histamine release syndrome in animals. PK was examined in cycle (cy) 1. MTD is the level below that where 2 of 3-6 pts have DLT during cy 1-2. Study A: CBP501 day 1/8/15, q4w, initial dose 0.9 mg/m². Study B: q3w, initial CBP501/CDDP doses 3.6/50 mg/m². Results: Studies were run in 4 US centers from Jun-05 to Dec-07. A) 30 pts treated, M/F: 16/14, median age 61 (25-82), PS 0/1/2: 9/20/1, median 4 prior lines, colon (5 pts), pancreas/biliary (6), ovarian (6), melanoma (2), renal (2), NSCLC (2), other (7). Median cy/pt: 2 (1-8). All pts discontinued due to PD. 1 DLT occurred (transient asymptomatic G3 troponin elevation) at 22.5 mg/m² (top DL given). No other G3-4 adverse events (AEs) occurred; 13 pts (43%) had G1-2 allergy. MTD was not reached. 2 pts (pancreas, ovarian) had SD for 7 cy. B) 27 pts treated, M/F: 14/13, median age 61 (31-81), PS 0/1: 8/19, median 4 prior lines, mesothelioma (5), prostate (4), NSCLC (4), pancreas/biliary (3), esophageal (3), other (8). Two DLTs (G3 allergic reaction) occurred at CBP501/CDDP 36.4/75 mg/m². No other G3-4 AEs occurred. MTD was defined as 25 mg/m² CBP501, 75 mg/m² CDDP. Allergic reaction was the most common AE, observed in 12 (44%) pts. PR (unconfirmed) endometrial (7+ cy, CA125 50% drop); SD, 2 mesothelioma (11+, 5), adenoid cystic (8), neuroendocrine (4+), ovarian (3+, CA125 50% drop), NSCLC (3+). PK: CBP501 Cmax and AUC showed dose-proportionality, and no difference between day 1 and 15 for both studies. Conclusions: CBP501 was well tolerated, as single agent and with CDDP. The main toxicity was dose-limiting allergic reaction. Promising signs of efficacy are seen in pts already exposed to platinum. Phase I-II studies of CBP501/pemetrexed/CDDP are planned.
Abstract Disclosures
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy
and are designated with a caret symbol (^) here and in the print version.
 Associated Presentation(s):
Other Abstracts in this Sub-Category:
Abstracts by B. Y. Wong :
Presentations by B. Y. Wong :
Educational Book Manuscripts by B. Y. Wong :
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