| General information |
| Database: | DB00218 |
| Objective: | Therapeutic cancer vaccines have shown activity in metastatic castrationresistant prostate cancer (mCRPC), and methods are being assessed to enhance their efficacy. Ipilimumab is an antagonistic monoclonal antibody that binds cytotoxic Tlymphocyteassociated protein 4, an immunomodulatory molecule expressed by activated T cells, and to CD80 on antigenpresenting cells. They aimed to assess the safety and tolerability of ipilimumab in combination with a poxviralbased vaccine targeting prostatespecific antigen (PSA) and containing transgenes for Tcell costimulatory molecule expression, including CD80. |
| Authors: | Madan RA, et al |
| Title: | Ipilimumab and a poxviral vaccine targeting prostatespecific antigen in metastatic castrationresistant prostate cancer: a phase 1 doseescalation trial. |
| Journal: | Lancet Oncol |
| Year: | 2012 |
| PMID: | 22326924 |
| Trial Design |
| Clinical Trial Id: | NCT00113984 |
| Agent: | ipilimumab
|
| Target: | Cytotoxic Tlymphocyte antigen 4 (CTLA4)
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 11 |
| Therapeutic Combination Content: | ipilimumab + a fixed dose of the PSATricom vaccine |
| Study Type: | a phase I doseescalation trial |
| Key Patients Feature: | Patients with metastatic castrationresistant prostate cancer (mCRPC). 30 patients (24 of whom had not been previously treated with chemotherapy) |
| Biomarker: | PSA, CD80 |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | single arm |
| Treatment Info: | Patients with mCRPC received 2¡Á10(8) plaqueforming units of recombinant vaccinia PSATricom subcutaneously on day 1 of cycle 1, with subsequent monthly boosts of 1¡Á10(9) plaqueforming units, starting on day 15. Intravenous ipilimumab was given monthly starting at day 15, in doses of 1, 3, 5, and 10 mg/kg. |
| Primary End Point: | safety and tolerability of escalating doses of combination |
| Secondary End Point: | NA |
| Patients Number: | 30 |
| Trial Results |
| DLT_MTD: | no doselimiting toxic effects |
| Objective Response Rate: | Only one of the six patients previously treated with chemotherapy had a PSA decline from baseline. Of the 24 patients who were chemotherapynaive, 14 (58%) had PSA declines from baseline, of which six were greater than 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): | Grade 1 and 2 vaccinationsite reactions were the most common toxic effects: three of 30 patients had grade 1 reactions and 26 had grade 2 reactions. 21 patients had grade 2 or greater immunerelated adverse events. Grade 3 or 4 immunerelated adverse events included diarrhoea or colitis in four patients and grade 3 rash (two patients), grade 3 raised aminotransferases (two patients), grade 3 endocrine immunerelated adverse events (two patients), and grade 4 neutropenia (one patient). |
| Conclusions: | The use of a vaccine targeting PSA that also enhances costimulation of the immune system did not seem to exacerbate the immunerelated adverse events associated with ipilimumab. Randomised trials are needed to further assess clinical outcomes of the combination of ipilimumab and vaccine in mCRPC. |