On September 10, 2017 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 final results from the dose-selection phase of an ongoing Phase 1/2 trial investigating IMO-2125, Idera’s intratumorally-delivered Toll-like Receptor (TLR) 9 agonist, in combination with ipilimumab (Yervoy), manufactured by Bristol-Myers Squibb (Press release, Idera Pharmaceuticals, SEP 10, 2017, View Source [SID1234520451]). These data were presented at the 2017 European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) in Madrid, Spain.
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The IMO-2125-ipilimumab dose-selection phase included 18 patients, all but one of whom had progressed on nivolumab or pembrolizumab. Patients were treated with up to 6 doses of intratumoral IMO-2125 at doses ranging from 4 to 32 mg, along with standard dosing of ipilimumab. No dose-limiting toxicities were seen and the maximum tolerated dose (MTD) was not reached. No previously unreported immune-related toxicities were observed. The 8 mg IMO-2125 dose was selected for further development in combination with ipilimumab based upon acceptable safety, clinical activity, and evidence for target engagement on serial biopsies of the injected tumor and a distant (non-injected) metastasis.
Key Findings
Nine patients were treated at the Recommended Phase 2 Dose (RP2D) of 8 mg IMO-2125 (in combination with ipilimumab)
Confirmed RECIST v1.1 responses (including 1 Complete Response (CR) ≥ 1 year) were observed in 4 of these 9 subjects (44%);
Overall 6 patients out of 9 treated at the RP2D (67%) experienced disease control (CR, PR, or durable SD);
A RECIST v1.1 PR of > 1 year duration is ongoing in a patient treated with IMO-2125 4 mg (in combination with ipilimumab);
IMO-2125 in combination with ipilimumab is tolerable at all dose levels studied
IMO-2125 was safely administered via deep injection (using interventional radiology guidance) in patients lacking superficially accessible disease for injection
Dose escalation with IMO-2125 and pembrolizumab is ongoing; one patient has an ongoing PR by RECIST (v1.1), and;
An abstract highlighting translational findings from the trial has been accepted as an oral presentation for the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting in November.
"The majority of patients with solid tumors do not respond to anti-PD-1 therapy and the published response rate to ipilimumab alone in anti-PD-1 refractory melanoma is only10-13%; to be seeing 6 out of 9 patients experiencing clear disease control is extremely exciting," stated Adi Diab, M.D., Lead Trial Investigator, Assistant Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center.
"Based on these positive and encouraging response data in anti-PD-1 refractory melanoma, where the greatest need exists, we have expanded the target number of patients in the ongoing Phase 2 expansion, including broadening eligibility to patients who have received prior ipilimumab, including the ipilimumab/PD-1 inhibitor combination," stated Joanna Horobin, M.B., Ch.B., Idera’s Chief Medical Officer. "We plan to start a Phase 3 trial in patients with PD-1 refractory melanoma in the first quarter of 2018. Preparations are well-underway for this global initiative which is addressing a major unmet need in melanoma. We are very encouraged by the enthusiasm of investigators to participate in the Phase 3 study."
A copy of the poster presentation is currently available on Idera’s corporate website at View Source." target="_blank" title="View Source." rel="nofollow">View Source
About the Phase 1/2 trial of IMO-2125 in combination with ipilimumab (NCT02644967)
Study 2125-204 is a Phase 1/2 open-label study of intratumoral IMO-2125 given in combination with either ipilimumab or pembrolizumab to patients with PD-(L)1 refractory melanoma with a planned enrollment of approximately 90 patients. IMO-2125 is given in escalating dosages from 4 to 32 mg combined with either ipilimumab (3 mg/kg i.v. every 3 weeks for 4 doses) or pembrolizumab (2 mg/kg i.v. every 3 weeks). Study endpoints are safety, tumor response, pharmacodynamics, and pharmacokinetics. Serial biopsies of both the injected and a distant tumor are being performed for translational immunologic studies. Preliminary data, presented at SITC (Free SITC Whitepaper) 2016, ASCO (Free ASCO Whitepaper)-SITC 2017, AACR (Free AACR Whitepaper) 2017, and CRI-CIMT-EATI-AACR 2017 are available on Idera’s website (View Source).
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.