Abstract B72: Long-term survival and outcome update on patients (pts) with recurrent ovarian cancer who received Ipilimumab post GVAX vaccine.
Authors: Matulonis Ursula Anne , Hodi Stephen , Dranoff Glenn , Campos Susana , Penson Richard , Soiffer Robert , Butler Marcus 
Published: May 2016

Immunotherapeutic approaches are amongst the most exciting new therapies for cancer, and trials of immunotherapy agents to treat ovarian cancer are underway. We report on long-term outcomes of patients with advanced and recurrent ovarian cancer treated with single agent ipilimumab, a fully humanized IgG1 monoclonal antibody against CTLA-4, following receipt of GVAX vaccine, which was a lethally irradiated, autologous ovarian cancer cells engineered by adenoviral gene transfer to secrete granulocyte macrophage colony stimulating factor (GM-CSF). The objectives of this study were to determine the safety of ipilimumab, identify preliminary evidence of biologic activity and efficacy of ipilimumab post GVAX, and, as an exploratory objective, to correlate clinical benefit with the presence of antibodies to NY-ESO and p53.

Results: Eleven pts who initially were treated with GVAX received ipilimumab (3 mg/kg) IV every 2 months on this study. These 11 patients had a median age of 61 years (range 38-82 years of age) at the time on enrollment and all had measureable cancer by RECIST 1.0. Eight pts had platinum resistant cancer and 3 had platinum sensitive cancer. Histologies enrolled were high grade serous (8 pts), clear cell (1pt), poorly differentiated (1 pt), and low grade serous that had evolved to high grade (1 pt). Patients were allowed to have had intervening treatment between initial GVAX vaccine and start of ipilimumab. Of the 11 pts, the median interval between GVAX and ipilimumab was 3 months, ranging from 1 month to 38 months.

Overall, ipilimumab at 3 mg/kg was well tolerated; rash was grade 1 (63%), grade 2 (9%), grade 3 (9%). Diarrhea was 18% grade 2 and 18% grade 3. Other constitutional symptoms such as fatigue were 18% grade 1 and 9% grade 3. Of the 11 pts, 6 pts had disease progression by RECIST after 1 infusion of ipilimumab with overall survival post-ipilimumab ranging from 3 to 35 months; 2 of these pts had platinum sensitive recurrence. Of the 5 pts who either experienced SD (4 pts) and PR (1 pt), the number of ipilimumab infusions were 1, 2 (2 pts), 4, and 25 infusions with survival ranging from 23 to 104 months post-ipilimumab. One patient (OV65) who received 25 ipilimumab infusions from 2003 through 2011 lived for 104 months post-initiation of ipilimumab and had a PR to ipilimumab at 95 months; she had high grade serous platinum resistant cancer with spread to liver/omentum/lymph nodes, had present NY-ESO Ab's, and had a 1 month interval between GVAX and the initiation of ipilimumab infusions. OV65 received no further chemotherapy treatment after ipilimumab was started though she had evidence of cancer present during her ipilimumab treatment course; her eventual death was not cancer related.

Conclusions: CTLA-4 blockade with ipilimumab can induce long-term disease control and has evidence of activity in ovarian cancer. The role of prior GVAX vaccination is not clear.

Citation Format: Ursula Anne Matulonis, Stephen Hodi, Glenn Dranoff, Susana Campos, Richard Penson, Robert Soiffer, Marcus Butler. Long-term survival and outcome update on patients (pts) with recurrent ovarian cancer who received Ipilimumab post GVAX vaccine. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B72.