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Heavily pretreated ovarian cancer patients who received a combination therapy of a novel engineered interleukin-2 (IL-2) cytokine plus pembrolizumab achieved an acceptable safety profile, according to a small cohort of an ongoing phase 1/2 trial.
The study also found limited evidence of tumor shrinkage and disease stabilization in some patients.
The ARTISTRY-1 trial is sponsored by Alkermes plc (Dublin, Ireland), maker of the cytokine ALKS 4230, which is administered intravenously as monotherapy and in combination with pembrolizumab.
“There is a large unmet need in the gynecological cancer space, especially for platinum-resistant ovarian cancer,” said principal investigator Ira Winer, MD, PhD, an associate professor of gynecologic oncology at Wayne State University and Karmanos Cancer Institute in Detroit.
Winer, who presented study results in November at the 35th annual meeting of the Society for Immunotherapy of Cancer (SITC), said patients with platinum resistant and refractory ovarian cancer “typically do not do well. Newer agents and therapeutic avenues are desperately needed.”
Although checkpoint inhibitors are approved to treat several types of cancer, they have limited success for ovarian cancer to date, according to Winer. “There is only about a 10% to 15% response rate in patients suitable for prototypical immune-oncology (IO) therapy,” he said. “The goal is to improve these outcomes.”
The combination phase of ARTISTRY-1, which comprises a subgroup of 15 ovarian cancer patients, was initiated at Karmanos Cancer Institute roughly 2 years ago. Patients range in age from 48 to 83, with an average age of 74.
Prior to the study, these ovarian cancer patients had received a median of five regimens, ranging from two to 11, and all were previously treated with platinum-based therapy.
Then, during the study period, each patient participated in one or more 21-day therapy cycles, with median treatment duration of roughly 7 weeks.
Each cycle consisted of ALKS 4230 (3 µg/kg) on days 1 through 5 and pembrolizumab (200 mg) on day 1 only.
Changes in tumor microenvironment (TME) were calculated using baseline and on-treatment biopsies.
Among 13 evaluable patients (at least one post-treatment assessment), 9 patients attained disease control or stable disease at first scan and the other 4 experienced disease progression.
Five patients experienced tumor shrinkage for more than 20 weeks, including 3 patients who experienced an objective response: 1 complete response (complete disappearance of cancer), 1 partial response and 1 unconfirmed partial response.
“All 3 of these patients were platinum resistant and negative for BRCA mutations,” Winer told Contemporary OB/GYN.
Unexpectedly, the patient with the complete response was heavily pretreated and has participated in the trial for well over 1 year. “Quality and quantity of life are important in patients with ovarian cancer, as with all disease, and this patient has seen both, despite being on such an intensive regimen,” Winer said.
He said for ovarian cancer, the study responses would be rare from checkpoint inhibitors alone. “In fact, a single checkpoint inhibitor response would be anecdotal,” he said. “We might see one or two patients respond, but not multiple, as we have seen in this small cohort of patients.”
Treatment-related adverse events at the doses tested have generally been transient and manageable, according to Winer, with the majority being grade 1 or grade 2 severity. The cytokine did not show any additive toxicity to that already established with pembrolizumab alone.
“The way ALKS 4230 is designed helps modulate the immune environment and immune cells themselves to make the prototypical checkpoint inhibitor work better,” Winer said. “Our results are one of the reasons we are starting to develop a Phase 2 study. We want to ensure that what are we observing in this smaller group of patients will translate to a larger population.”
Winer reports no relevant financial disclosures.