Date: 2015-12-14
Type of
information: Initiation of patient enrollment
phase: 1-2
Announcement: initiation of patient enrollment
Company: Idera Pharmaceuticals (USA - CA)
Product: IMO-2125 in combination with ipilimumab
Action
mechanism:
- monoclonal antibody/immune checkpoint inhibitor/TLR9 agonist/oligonucleotide. Idera's TLR9 agonist, IMO-2125 is a synthetic oligonucleotide-based agonist of Toll-like receptor 9. It has been shown to activate dendritic cells and induce interferon. Idera selected IMO-2125 to advance into clinical development in combination with checkpoint inhibitors based on this immunological profile.
Disease: patients with previously treated metastatic melanoma
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
Latest
news:
- • On December 14, 2015, Idera Pharmaceuticals announced that the company has commenced enrollment in a Phase 1/2 clinical trial evaluating intra-tumoral IMO-2125, a TLR9 agonist in combination with ipilimumab in patients with previously treated metastatic melanoma. The study is being conducted at The University of Texas MD Anderson Cancer Center and is being led by Adi Diab , MD, Assistant Professor, Department of Melanoma Medical Oncology , Division of Cancer Medicine , MD Anderson.
In this clinical trial, escalating doses of IMO-2125 ranging from 4 mg/kg through 32 mg/kg will be administered intra-tumorally into one of two selected tumor lesions, with a standard dosing regimen of ipilimumab. The primary objectives of the phase 1 portion of the trial will be to determine the maximum tolerated dose (MTD) and characterize the dose-limiting toxicities (DLTs) of IMO-2125 when administered intra-tumorally in combination with ipilimumab. The primary objective of the phase 2 portion will be to determine the efficacy of the combination utilizing the immune-related response criteria (irRC) in additional to traditional RECIST criteria. Serial biopsies will be taken of selected injected and non-injected tumor lesions to assess immune changes and response assessments. The trial will enroll approximately 45 patients. The company expects initial data from the ongoing trial to be available in 2016.
- • On November 5, 2015, Idera Pharmaceuticals announced new preclinical data demonstrating potent and systemic anti-tumor activity in preclinical cancer models with intra-tumoral administration of IMO-2125 in combination with an anti-PD-1 monoclonal antibody (mAb). These data are being presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston. In the presentation, entitled "Intra-tumoral administration of IMO-2125, a novel TLR9 agonist, modulates tumor microenvironment and potentiates antitumor activity of anti-PD-1 (mAb) in a murine colon carcinoma model," Idera scientists presented data providing evidence that intra-tumoral IMO-2125 administration changes the tumor microenvironment by increasing infiltration of tumor-infiltrating lymphocytes (TILs) and by modulating gene expression of multiple checkpoints, including PD-L1. In the study, treatment with a combination of intra-tumoral IMO-2125 with anti-PD-1 antibody showed more potent anti-tumor activity than either agent alone, with potent anti-tumor activity observed on treated as well as distant tumors. Additionally, increased infiltration levels of TILs and increased PD-L1 and other checkpoint expression was observed in both treated and distant tumors.
- • On September 16, 2015, Idera Pharmaceuticals announced new preclinical data that showed cancer immunotherapy with intratumoral injections of IMO-2125 alone and in combination with ipilimumab demonstrated potent and systemic anti-tumor activity in preclinical cancer models. Additionally, Idera presented preclinical data which demonstrated that IMO-2125 induces a systemic antitumor immune response with the potential to sensitize the tumor microenvironment for combination with various checkpoint inhibitors. These data are being presented at the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference in New York City. In the presentation, entitled "Intratumoral administration of IMO-2125, a novel TLR9 agonist, modulates the tumor microenvironment and exerts systemic antitumor activity alone and in combination with an anti-CTLA4 monoclonal antibody (mAb)," Idera scientists presented data suggesting that intratumoral IMO-2125 monotherapy led to dose-dependent decreases in treated and distant tumor volume, an increase in infiltrating CD8+ T cells and specific cytotoxic T cell responses against tumor antigens. Combination of intratumoral IMO-2125 and an anti-CTLA4 mAb showed improved inhibition of tumor growth, regression of systemic lung metastases and infiltration of TILs versus monotherapy with either agent. Collectively, these data demonstrate the potent antitumor activity of IMO-2125, a novel immunostimulatory TLR9 agonist, alone and in combination with a checkpoint inhibitor.
Idera expects to initiate the first clinical study of intratumoral IMO-2125 in combination with ipilimumab in patients with metastatic melanoma in the fourth quarter of this year as part of the previously announced clinical research alliance with MD Anderson Cancer Center (see below).
In the presentation, entitled "Modulation of checkpoint expression in tumor microenvironment by intratumoral administration of a novel TLR9 agonist: Rationale for combination therapy," Idera scientists presented data suggesting that intratumoral IMO-2125 treatment led to antitumor activity in preclinical tumor models of lymphoma, colon carcinoma and melanoma. Specifically, intratumoral IMO-2125 treatment resulted in changes in the tumor microenvironment in both treated and distant tumors, as demonstrated by modulation of immune checkpoint gene expression. These data showed that intratumoral IMO-2125 has the potential to sensitize the tumor microenvironment for combination with various checkpoint inhibitors.
- • On June 8, 2015, Idera Pharmaceuticals announced that the company has entered into a strategic clinical research alliance with The University of Texas MD Anderson Cancer Center to advance clinical development of intratumoral TLR9 agonist in combination with checkpoint inhibitors. IMO-2125 is a TLR9 agonist which has been evaluated subcutaneously in over 80 human subjects, was well tolerated, and was shown to induce immune responses.
The company intends to initiate the first trial of the research alliance, a Phase 1/2 study to assess the safety and efficacy of Intratumoral IMO-2125 in combination with ipilimumab (a CTLA4 antibody) in patients with metastatic melanoma. In this trial, escalating doses of IMO-2125 will be administered intratumorally into a lesion, with a standard dosing regimen of ipilimumab. The primary objectives of the trial will be to determine the maximum tolerated dose (MTD) and characterize the dose-limiting toxicities (DLTs) of IMO-2125 when administered intratumorally in combination with ipilimumab, as well as to determine the efficacy of the combination utilizing the immune-related response criteria (irRC). The company has already filed and received FDA feedback to a Pre-Investigational New Drug Application (PIND) for IMO-2125 and intends to submit an Investigational New Drug application (IND) and initiate the clinical study in the second half of this year. The trial will enroll approximately 45 patients. The company expects data to be available in 2016. The study will be led by Adi Diab , MD, Assistant Professor, Department of Melanoma Medical Oncology , Division of Cancer Medicine , MD Anderson. Additional trials as part of the broader, clinical research alliance are currently in the planning stages.
Is
general: Yes
