Phase 3 Study Resumes to Evaluate Sargramostim Combo to Treat Melanoma

Enrollment in the randomized controlled EA6141 study analyzing sargramostim (Leukine) in combination with ipilimumab (Yervoy) and nivolumab (Opdivo) for the front-line treatment of melanoma has resumed, according to a Partner Therapeutics, Inc. press release.

The resumption is based on results from ECOG-ACRIN Cancer Research Group’s planned interim efficacy and safety analysis regarding survival data for the first 250 patients enrolled in the study.

"GM-CSF has unique immunomodulatory properties that have the potential to substantially benefit patients with cancer,” study chair F. Stephen Hodi, MD, said in a press release. “I am particularly pleased, given the many years we have spent in understanding the role of GM-CSF in the laboratory and the clinical setting.”

The phase 2/3 EA6141 study was initially launched in September 2015 and was paused after the enrollment of 240 patients. The researchers analyzed patients with stage III/IV unresectable melanoma who were randomized to receive standard of care treatment combined with nivolumab and ipilimumab with or without sargramostim.

Enrollment was paused in June 2017 to assess efficacy of the combination. The primary endpoint for the research was overall survival. Based on the data from the interim analysis, the study was approved for enrollment in the phase 3 portion of the research, which remains a blinded study.

"This study in the front line setting is intended to confirm and broaden the findings in the randomized phase 2 trial EA1608, which demonstrated improved efficacy and toxicity when sargramostim was added to ipilimumab," said Hodi.

Results were reported from the previous E1608 phase 2 study analyzing a combination of sargramostim and ipilimumab or ipilimumab alone for patients with advanced stage melanoma. For the 245 patients enrolled, adding sargramostim led to longer survival (median, 17.5 vs 12.7 months; HR, 0.64). For adverse events, severe toxicities occurred less frequently in patients treated with sargramostim plus ipilimumab than ipilimumab alone (44.9% vs 58.3%, Grade 3-5).

Melanoma is the most aggressive form of skin cancer, with the American Cancer Society estimating that 96,480 new melanoma cases will be diagnosed in the United States and 7230 deaths in 2019.

"The prior data with sargramostim supporting improvement in survival and reduction in immune-related toxicity, as observed in the E1608 study, highlights the importance of further clinical evaluation in combination with checkpoint inhibitors," study co-chair Ahmad Tarhini, MD, PhD, said in a press release. "EA6141 is a very important study in front line melanoma with the possibility of changing the standard of care and I expect a rapid enrollment across a large number of centers throughout the U.S.”

Reference:

Partner Therapeutics Announces Start of Phase 3 Portion of Clinical Study of Leukine® in Combination with Ipilumimab and Nivolumab in Front Line Treatment of Melanoma [news release]. Lexington, Massachusetts. Published September 11, 2020. https://www.prnewswire.com/news-releases/partner-therapeutics-announces-start-of-phase-3-portion-of-clinical-study-of-leukine-in-combination-with-ipilumimab-and-nivolumab-in-front-line-treatment-of-melanoma-301128104.html. Accessed September 11, 2020.