| General information |
| Database: | DB00220 |
| Objective: | They recently reported the clinical results of a phase I trial combining ipilimumab with a vaccine containing transgenes for prostatespecific antigen (PSA) and for a triad of costimulatory molecules (PROSTVAC) in patients with metastatic castrationresistant prostate cancer. 30 patients were treated with escalating ipilimumab and a fixed dose of vaccine. Of 24 chemotherapyna ve patients, 58 % had a PSA decline. Combination therapy did not exacerbate the immunerelated adverse events associated with ipilimumab. Here, they present updated survival data and an evaluation of 36 immune cell subsets pre and posttherapy. |
| Authors: | Jochems C, et al |
| Title: | A combination trial of vaccine plus ipilimumab in metastatic castrationresistant prostate cancer patients: immune correlates. |
| Journal: | Cancer Immunol Immunother |
| Year: | 2014 |
| PMID: | 24514956 |
| 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: | Peripheral blood mononuclear cells were collected before therapy, at 13 days and at 70 days postinitiation of therapy, and phenotyped by flow cytometry for the subsets of T cells, regulatory T cells, natural killer cells, and myeloidderived suppressor cells. |
| Primary End Point: | Associations between overall survival (OS) and immune cell subsets prior to treatment, and the change in a given immune cell subset 70 days postinitiation of therapy |
| Secondary End Point: | NA |
| Patients Number: | 30 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | median OS was 2.63 yrs(1.773.45).There were trends toward associations for longer OS and certain immune cell subsets before immunotherapy: lotheyr PD1(+)Tim3(NEG)CD4EM (P = 0.005, adjusted P = 0.010), higher PD1(NEG)Tim3(+)CD8 (P = 0.002, adjusted P = 0.004), and a higher number of CTLA4(NEG) Tregs (P = 0.005, adjusted P = 0.010). They also found that an increase in Tim3(+) natural killer cells post versus prevaccination associated with longer OS (P = 0.0074, adjusted P = 0.015). |
| Adverse Event(agent arm): | NA |
| Conclusions: | These results should be considered as hypothesis generating and should be further evaluated in larger immunotherapy trials. |