A Pilot Study of Anti-CTLA4 Antibody Ipilimumab in Patients with Synovial Sarcoma

Robert G Maki, Achim A Jungbluth, Sacha Gnjatic, Gary K Schwartz, David R D'Adamo, Mary Louise Keohan, Michael J Wagner, Kelly Scheu, Rita Chiu, Erika Ritter, Jennifer Kachel, Israel Lowy, Lloyd J Old, Gerd Ritter, Robert G Maki, Achim A Jungbluth, Sacha Gnjatic, Gary K Schwartz, David R D'Adamo, Mary Louise Keohan, Michael J Wagner, Kelly Scheu, Rita Chiu, Erika Ritter, Jennifer Kachel, Israel Lowy, Lloyd J Old, Gerd Ritter

Abstract

Background. Patients with recurrent synovial sarcomas have few options for systemic therapy. Since they express large amounts of endogenous CT (cancer testis) antigens such as NY-ESO-1, we investigated the clinical activity of single agent anti-CTLA4 antibody ipilimumab in patients with advanced or metastatic synovial sarcoma. Methods. A Simon two-stage phase II design was used to determine if there was sufficient activity to pursue further. The primary endpoint was tumor response rate by RECIST 1.0. Patients were treated with ipilimumab 3 mg/kg intravenously every 3 weeks for three cycles and then restaged. Retreatment was possible for patients receiving an extra three-week break from therapy. Sera and peripheral blood mononuclear cells were collected before and during therapy to assess NY-ESO-1-specific immunity. Results. Six patients were enrolled and received 1-3 cycles of ipilimumab. All patients showed clinical or radiological evidence of disease progression after no more than three cycles of therapy, for a RECIST response rate of 0%. The study was stopped for slow accrual, lack of activity, and lack of immune response. There was no evidence of clinically significant either serologic or delayed type hypersensitivity responses to NY-ESO-1 before or after therapy. Conclusion. Despite high expression of CT antigens by synovial sarcomas of patients treated in this study, there was neither clinical benefit nor evidence of anti-CT antigen serological responses. Assessment of the ability of synovial sarcoma cell lines to present cancer-germ cell antigens may be useful in determining the reason for the observed lack of immunological or clinical activity.

Figures

Figure 1
Figure 1
One study patient demonstrated an immune response to a CTA after ipilimumab administration. Plots demonstrating immune titers in each patient to the specified CTA before ipilimumab and at weeks 4, 7, and 10 are presented. Only patient SS-F06 reproducibly showed a weak preexisting serum antibody response to MAGEA3 and MAGEA4, that increased after treatment. Patient SS-F06 also had serum antibodies to CT47 throughout the study that did not change in titers and seroconversion against CSAG2 after the first ipilimumab injection. Patient SS-C03 had some reactivity to SOX2 and had a transient response to CSAG2.

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