Abstract No.: 5004
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 5004)
Author(s):
T. M. Beer, S. F. Slovin, C. S. Higano, S. Tejwani, T. B. Dorff, E. Stankevich, I. Lowy, Prostate Cancer Clinical Trials Consortium
Background: IPI is a fully human, anti-CTLA 4 monoclonal antibody capable of enhancing anti-tumor immunity. In preclinical models, XRT results in tumor antigen release and enhances anti-tumor activity of CTLA-4 blockade.
Methods: Pts with mCRPC and ECOG PS of 0-1 were treated with escalating doses of IPI every 3 weeks X 4 doses in cohorts of 6 pts at dose levels of 3, 5, and 10 mg/kg. After the 10 mg/kg cohort was completed, a protocol amendment added single fraction XRT prior to IPI starting at the 3 mg/kg dose level. The primary endpoint was safety. Imaging was repeated every 3 months and serum PSA was monitored monthly.
Results: Between 1/2006 and 12/2007, 8, 6, and 6 pts were treated at the 3, 5, and 10 mg/kg dose levels respectively; 6 pts were then treated in the first XRT cohort for a total of 26 pts. 19 pts experienced 29 immune-related adverse events (irAEs) including diarrhea/colitis (14), rash (9), hepatitis (4), endocrinopathy (2). irAEs were > Grade 3 in 9 pts: GI (6), hepatitis (2), and rash (1) and were generally responsive to immunosuppression. One pt died of opportunistic infections (OI) after 3 months of immunosuppression for colitis; this prompted inclusion of OI prophylaxis within the treatment algorithms. Another pt continues (1yr+) on immunosuppression to suppress colitis. Six pts (23%, 95% CI: 9-44%), all with irAEs, had a confirmed >50% PSA decline (median duration 140d, range 49 to 269+; median time to PSA decline 84d, range 41 to 147). 1 of 7 pts with measurable disease had a PR in nodal metastases and the prostate and achieved an undetectable PSA after treatment with 10 mg/kg IPI. Measurable disease response and PSA decline are both ongoing for 185+, 269+ d, respectively.
Conclusions:
The irAEs seen in this trial are similar in type to those seen in melanoma trials with IPI. Antitumor activity appears associated with irAEs. Both irAEs and PSA declines were seen across dose levels. Addition of XRT to 3 mg/kg appears feasible, and evaluation of radiation with 10 mg/kg of IPI is underway.