Guadecitabine Yields Modest Anti-Tumor Activity in Platinum-Resistant Ovarian Cancer

Guadecitabine as a primer for pembrolizumab treatment has modest anti-tumor activity in patients with advanced, platinum-resistant, recurrent ovarian cancer, according to data from a phase 2 study presented at the virtual 2020 ASCO Annual Meeting.

“Platinum resistant ovarian cancer…remains a disease of high need,” wrote Daniela Matei, MD, Northwestern University Feinberg School of Medicine, Chicago, Illinois, and co-investigators on the importance of additional research in this area.

The researchers hypothesized that priming with a hypomethylating agent, guadecitabine, would improve the anti-tumor activity of immune checkpoint inhibitors in treating platinum-resistant ovarian cancer by enhancing tumor cell recognition by CD8-positive T-cells.

A total of 48 patients were enrolled in the Simon’s 2-stage design study. Eligible patients had platinum-resistant ovarian cancer, an Eastern Cooperative Oncology Group (ECOG) performance status score 0-1, measurable disease, and normal end organ function.

The primary end point was response rate; additional end points were progression-free survival, clinical benefit rate, and toxicity.

Treatment consisted of 21-day cycles of guadecitabine 30 mg/m2 and pembrolizumab 200 mg.

Ultimately, 33 patients were evaluable for response. Of these patients, 16 (48%) had stable disease and 2 had partial responses. The clinical benefit rate was determined to be 27%.

The most common grade 3-4 toxicities were neutropenia and lymphopenia. There were 13 serious grade 3-4 adverse events, as well as 4 grade 5 serious adverse events, unrelated to treatment.

“Guadecitabine plus pembrolizumab has modest anti-tumor activity in patients with platinum resistant ovarian cancer, but some patients experienced prolonged disease stabilization,” summarized Dr Matei and colleagues, who added that biomarkers of response are being evaluated.—Alexis Hyams

Matei D, Pant A, Moroney JW, et al. Phase II trial of guadecitabine priming and pembrolizumab in platinum resistant recurrent ovarian cancer. Presented at: the 2020 ASCO Annual Meeting; May 29-31, 2020. Abstract 6025.