On March 1, 2018 Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a clinical-stage biopharmaceutical company developing toll-like receptor and RNA therapeutics for patients with rare cancers and rare diseases, reported the start of a Phase 3 global, multi-center, open-label clinical trial to evaluate the efficacy and safety of intratumoral IMO-2125 in combination with ipilimumab (Yervoy) versus ipilimumab alone in subjects with anti-PD-1 refractory melanoma (NCT03445533) (Press release, Idera Pharmaceuticals, MAR 1, 2018, View Source [SID1234524649]). The initiation of the Phase 3 trial follows the announcement that IMO-2125 was granted Fast-Track designation by the U.S. Food and Drug Administration, a designation designed to expedite the development and review of drugs with the potential to treat serious or life-threatening conditions such as refractory metastatic melanoma.
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Results presented at the 2017 European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) meeting from the completed phase 1 portion of the ongoing Phase 1/2 clinical trial of intratumoral IMO-2125 in combination with ipilimumab (NCT02644967) show the combination to be well-tolerated over the entire range of IMO 2125 doses tested, with biopsy evidence for dendritic cell activation followed by infiltration of tumor specific immune cells. These results included 9 patients treated with the Recommended Phase 2 Dose (RP2D) of 8mg of which 4 (44%) achieved RECIST v1.1 responses, including one durable Complete Response (CR), with 6 of 9 (67%) patients experiencing disease control (CR, PR, or SD ≥ 12 weeks).
"For our advanced melanoma patients who have not benefited from anti-PD-1 therapy and in BRAF mutant melanoma, BRAF targeted therapy, there are very few, limited options available today," stated Ahmad Tarhini, M.D., Ph.D, Director, Melanoma and Skin Cancer Program, Cleveland Clinic Taussig Cancer Institute. "I am encouraged by the data that has been demonstrated to date with IMO-2125 and am hopeful that this Phase 3 trial offers hope to this large group of patients whose treatment options are very limited."
"We are excited to initiate the ILLUMINATE 301 Trial, grateful to our advisors who have worked with us to design this pivotal trial and very encouraged by the enthusiasm of investigators to participate in the study. We look forward to working together to conduct and complete this trial, so that we may bring IMO-2125 to the market as soon as possible for patients who are not benefiting from anti-PD-1 therapy," stated Joanna Horobin, M.B., Ch.B., Idera’s Chief Medical Officer.
ILLUMINATE 301 Trial Design
ILLUMINATE 301 is planned in approximately 80 sites, across 10 countries, and expected to enroll approximately 300 subjects with advanced melanoma who have confirmed disease progression while on nivolumab (Opdivo) or pembrolizumab (Keytruda). Subjects will be randomized into two treatment arms (IMO-2125 in combination with ipilimumab vs. ipilimumab monotherapy). Subjects must have histologically confirmed metastatic melanoma with measurable (by Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), Stage III (lymph node or in transit lesions) or Stage IVA, IVB, or IVC disease, and at least one lesion that is accessible for injection.
This Phase 3 study is being performed to provide definitive evidence for superiority of the IMO-2125 and ipilimumab combination over ipilimumab. The reported overall response rate for ipilimumab monotherapy following anti-PD-1 therapy is 13%1. The primary endpoint family includes overall survival and overall response rate. For more information on the study and patient qualifications, visit www.ideraclinicaltrials.com.
About IMO-2125
IMO-2125 is a toll-like receptor (TLR) 9 agonist that received orphan drug designation from the US Food and Drug Administration (FDA) in 2017 for the treatment of melanoma Stages IIb to IV. It signals the immune system to create and activate cancer-fighting cells (T-cells) to target solid tumors in refractory melanoma patients. Currently approved immuno-oncology treatments for patients with metastatic melanoma, specifically check-point inhibitors, work for some but not all, as many patients’ immune response is missing or weak and thus they do not benefit from the checkpoint therapy making them so-called "refractory." The combination of ipilimumab and IMO-2125 appears to activate an immune response in these patients who have exhausted all options. Intratumoral injections with IMO-2125 are designed to selectively enable the T-cells to recognize and attack cancers that remained elusive and unrecognized by the immune system exposed to checkpoint inhibitors alone, while limiting toxicity or impact on healthy cells in the body.
About Metastatic Melanoma
Melanoma is a type of skin cancer that begins in a type of skin cell called melanocytes. As is the case in many forms of cancer, melanoma becomes more difficult to treat once the disease has spread beyond the skin to other parts of the body such as the lymphatic system (metastatic disease). Because melanoma occurs in younger individuals, the years of life lost to melanoma are also disproportionately high when compared with other cancers. Although melanoma is a rare form of skin cancer, it comprises over 75% of skin cancer deaths. The American Cancer Society estimates that there were approximately 76,000 new invasive melanoma cases and 10,000 deaths from the disease in the USA in 2016. Additionally, according to the World Health Organization, about 132,000 new cases of melanoma are diagnosed around the world every year.