On September 11, 2020 Partner Therapeutics, Inc. (PTx), a commercial biotech company, reported the resumption of enrollment in the National Cancer Institute (NCI) sponsored Study EA61411 being conducted by ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and led by Study Chair F. Stephen Hodi, MD, Director of the Center for Immuno-Oncology at Dana-Farber Cancer Institute and Study Co-Chair Ahmad Tarhini, MD, PhD., Professor of Oncologic Sciences and Director of Cutaneous and Clinical Translational Research at H. Lee Moffitt Cancer Center and Research Institute (Press release, Partner Therapeutics, SEP 11, 2020, View Source [SID1234565038]).
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EA6141 (NCT02339571) is a randomized controlled study of Leukine (sargramostim, yeast derived rhu-GM-CSF) in combination with ipilimumab and nivolumab for the front line treatment of melanoma. The restart was based on results of ECOG-ACRIN’s planned interim efficacy and safety analysis of survival data from the first 250 patients enrolled in the study. In September 2019 the U.S. Food and Drug Administration (FDA) granted orphan drug status to Leukine, for the potential treatment of stage IIb-IV melanoma.
"GM-CSF has unique immunomodulatory properties that have the potential to substantially benefit patients with cancer. 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," said Dr. Hodi. He added "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."
ECOG-ACRIN launched the Phase 2/3 EA6141 study in September 2015. In the study, patients with stage III/IV unresectable melanoma are randomized to receive standard of care treatment with nivolumab and ipilimumab with or without sargramostim. The primary endpoint is overall survival. ECOG-ACRIN planned for the interim trial pause after 240 patients were enrolled, to assess efficacy. The group paused enrollment in June 2017 and the interim analysis is now complete. Based on the findings of the interim analysis, the ECOG-ACRIN Data Safety Monitoring Committee has given the go ahead to start the enrollment into the phase 3 portion of the study. The total planned enrollment is 600 patients. The study remains blinded and no data will be released until completion.
"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," said Dr Tarhini. "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.," he added.
"I wish to thank the ECOG-ACRIN group and the NCI for their diligence in the conduct of EA6141 leading to the transition into the phase 3 portion of the study," said Fiona Garner, executive director of clinical development at Partner Therapeutics. "Sargramostim has proven immunologic effects through enhanced T cell priming as well as the ability to repair and restore inflamed tissue, which can result in positive benefits in both efficacy and safety as a combination therapy with checkpoint inhibitors."
ECOG-ACRIN previously reported results of Study E1608, a Phase II study in which patients with advanced stage melanoma received a combination of sargramostim and ipilimumab or ipilimumab alone2. Among 245 patients, the addition of sargramostim led to longer survival (median 17.5 vs 12.7 months, HR 0.64). The most common Grade 3-5 toxicities in patients treated with sargramostim and ipilimumab were diarrhea (12.7%) and rash (9.3%), which occurred at similar rate in patients receiving ipilimumab alone. Overall, severe toxicities occurred less frequently in patients treated with sargramostim plus ipilimumab vs ipilimumab alone (44.9% vs 58.3%, Grade 3-5); the most notable reductions were in gastrointestinal (16.1% vs 26.7%) and pulmonary toxicities (0% vs 7.5%).2
Leukine is currently not approved for the treatment of melanoma. The approval of an orphan drug designation request does not alter the standard regulatory requirements and processes for obtaining marketing approval of an investigational drug. Sponsors must establish safety and efficacy of a compound in the treatment of a disease through adequate and well-controlled studies.
For additional information about the trial visit ECOG-ACRIN.org and ClinicalTrials.gov Identifier NCT02339571.
ABOUT LEUKINE
LEUKINE (sargramostim) is a recombinant yeast derived human granulocyte-macrophage growth factor (rhuGM-CSF) that stimulates the differentiation, maturation and mobilization of cells involved in the innate and adaptive immune response. It is an important immune modulator that has been shown to facilitate cellular signaling, epithelial repair, and other critical processes that enhance the immune response and help defend the body against infection and cancer. Partner Therapeutics acquired the rights to Leukine in 2018. Leukine is held by the U.S. Government in the Strategic National Stockpile for use during public health emergencies. Leukine is available outside of the United States through a Named Patient Program administered by Tanner Pharma Group.
ABOUT MELANOMA
Melanoma is the most aggressive form of skin cancer and rates of melanoma have been rising for the past 30 years. The American Cancer Society estimates 96,480 new melanoma cases will be diagnosed in the US and 7,230 people will die from the disease in 2019. The FDA grants orphan drug designation to promote the development of promising treatments for conditions that affect 200,000 or fewer U.S. patients annually.