| General information |
| Database: | DB00217 |
| Objective: | Blockade of the Tcell inhibitory receptor CTLassociated antigen4 (CTLA4) augments and prolongs Tcell responses and is a strategy to elicit antitumor immunity. The objectives of this pilot study were to establish the pharmacokinetic and safety profile for a single dose of 3 mg/kg of the antiCTLA4 antibody Ipilimumab (MDX010, BMS734016) and to assess if this therapy resulted in prostatespecific antigen (PSA) modulation and the development of polyclonal Tcell activation and/or clinical autoimmunity in patients with hormonerefractory prostate cancer treated with Ipilimumab. |
| Authors: | Small EJ, et al |
| Title: | A pilot trial of CTLA4 blockade with human antiCTLA4 in patients with hormonerefractory prostate cancer. |
| Journal: | Clin Cancer Res |
| Year: | 2007 |
| PMID: | 17363537 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | ipilimumab
|
| Target: | Cytotoxic Tlymphocyte antigen 4 (CTLA4)
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | A pilot trial |
| Key Patients Feature: | Eligible patients had histologically confirmed adenocarcinoma of the prostate with evidence of metastatic spread on imaging studies and evidence of disease progression despite androgen deprivation (and if applicable, antiandrogen withdrawal) as defined by the PSA Consensus Criteria |
| Biomarker: | PSA |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | single arm |
| Treatment Info: | pts received a single 3 mg/kg i.v. dose of Ipilimumab. Serologic measures of autoimmunity were obtained, and Tcell activation was evaluated by flow cytometry. Pharmacokinetic sampling of plasma for MDXCTLA4, PSA measurement, and diagnostic imaging were also undertaken. |
| Primary End Point: | safety and efficacy |
| Secondary End Point: | NA |
| Patients Number: | 14 |
| Trial Results |
| DLT_MTD: | 12 patients received a single dose of Ipilimumab, and 2 patients were retreated with a second dose upon PSA progression |
| Objective Response Rate: | Two patients showed PSA declines of > or =50%. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Treatment was well tolerated with clinical autoimmunity limited to one patient who developed grade 3 rash/pruritus requiring systemic corticosteroids. |
| Conclusions: | A single dose of 3 mgkg Ipilimumab, an antiCTLA4 antibody, given to patients with prostate cancer is safe and does not result in significant clinical autoimmunity. PSAmodulating effects observed warrant further investigation. |