During the 2022 Global Annual Meeting of the International Gynecologic Cancer SocietyCancerNetwork® spoke to Lilian Gien, MD, a gynecologic oncologist at Sunnybrook Health Sciences Center in Toronto, Canada, about the results of a Phase 2 study (NCT03602586) evaluating pembrolizumab (Keytruda) plus the IDO1 inhibitor epacadostat.
The objective response rate was 21% (95% CI, 0.05-0.51) and patients had a median duration of response of 6.9 months. Of a cohort of 14 patients, 3 had partial responses and 4 had stable disease with a disease control rate of 50%. In addition, the median progression-free survival was 4.8 months (95% CI, 1.9-9.6) and the median overall survival was 18.9 months (95% CI, 1.9-not reached).
Although the investigators ultimately concluded that the results were inconclusive for determining a benefit of adding epacadostat to pembrolizumab in this setting, the results were thought-provoking and added to what is known about the use of immunotherapies.
We know that recurrent clear cell ovarian cancer is an area of unmet need. We know that in all phase 2 studies conducted in all epithelial ovarian cancers involving clear cells, the response to immunotherapy monotherapy is approximately 15%. In these studies we have seen that clear cell carcinoma in particular appears to have a more pronounced and enduring response than other types of ovarian cancer. We thought we could build on that by seeing if we could improve the 15% overall response rate with combination therapy, particularly in ovarian cancer, which is clear cell and otherwise poorly responsive to chemotherapy.
This was a phase 2, single-arm study in recurrent or metastatic clear cell cancer of the ovary. We gave 2 drugs, one was pembrolizumab at 200 mg intravenously every 3 weeks and an IDO1 inhibitor called epacadastat given orally at 100 mg twice a day. The combination of these 2 was administered together until progression or toxicity, and overall response rate was the primary endpoint. There was approximately a 21% overall response rate. This was in a small cohort of patients. The plan for the sample size was to recruit enough patients for the first phase and, if the response was sufficient, to open the second phase for a total of 23 patients. We quickly recruited the first 14 patients in the first phase and carried out the analysis based on this. Due to a number of logistical issues, we were unable to complete the study to the full 23 patients. In the small cohort we had of 14 patients, the response rate was 21%.
There were mostly grade 1 and 2 side effects, things like nausea, vomiting and some electrolyte abnormalities. The grade 3 side effects were things like bowel obstruction, and there were some feeding issues as well. Overall, the vast majority were grades 1 and 2.
Gien LT, Enseroo DM, Block MS, et al. Phase II study of pembrolizumab and epacadostat in recurrent clear cell ovarian cancer: an NRG oncology study (NRG-GY016). Presented at: 2022 Annual Global Meeting of the International Gynecologic Cancer Society; New York, NY; September 29 – October 1, 2022. Summary O014.