Date: 2015-12-05
Type of
information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the 57th American Society of Hematology (ASH) Annual Meeting in Orlando
Company: Idera Pharmaceuticals (USA - CA)
Product: IMO-8400 - antagonist of the endosomal Toll-like receptors (TLRs) 7, 8, and 9
Action
mechanism:
- Toll-like receptor (TLR) antagonist/oligonucleotide. IMO-8400 is a first-in-class synthetic oligonucleotide-based antagonist of endosomal TLRs 7, 8, and 9. In April 2014, Idera presented preclinical data at the American Association for Cancer Research Annual Meeting from preclinical studies in which IMO-8400 inhibited the survival and proliferation of human B-cell lymphoma cells, including Waldenstrom’s macroglobulinemia (WM) cells, harboring the oncogenic MYD88 L265P genetic mutation. IMO-8400 has been well-tolerated in a Phase 1 trial in 42 healthy subjects at single and multiple escalating doses up to 0.6 mg/kg for four weeks, and has shown inhibition of immune responses mediated by TLRs 7, 8, and 9. Idera is pursuing clinical development of IMO-8400 in genetically defined forms of B-cell lymphoma, including WM and diffuse large B-cell lymphoma in patients harboring the MYD88 L265P mutation, and in rare autoimmune diseases, including dermatomyositis.
Disease: Waldenstrom's macroglobulinemia
Therapeutic
area: Cancer - Oncology - Rare diseases
Country:
Trial
details:
Latest
news:
- • On December 5, 2015, Idera Pharmaceuticals presented initial clinical data from its ongoing Phase 1/2 clinical trial for IMO-8400, a Toll-like receptor 7, 8 and 9 antagonist, being evaluated for the treatment of patients with relapsed or refractory Waldenström's Macroglobulinemia (WM). These results provide evidence that IMO-8400 has clinical activity and is well tolerated. These results were presented during a poster session (Abstract #1540 ) at the 57th Annual Meeting of the American Society of Hematology (ASH) in Orlando, FL.
The results being reported are from 15 evaluable patients with Waldenström's Macroglobulinemia who had a history of relapse or failure to one or more prior therapies and who completed at least one cycle of therapy with IMO-8400. Patients enrolled in the multi-center, open-label, dose ranging clinical trial which evaluated 3 dose levels of IMO-8400 (06. mg/kg weekly, 1.2 mg/kg weekly, 1.2mg/kg twice a week) administration for a period of up to 24 weeks. The primary objectives of the study were to assess safety and tolerability. Secondary objectives were to assess clinical activity, PK and define the optimal dose for further clinical evaluation. In addition to clinical treatment parameters, cytokine levels were analyzed as an exploratory endpoint in the trial.
Safety: IMO-8400 was generally well tolerated at all dose levels studied.
The Maximum Tolerated Dose of IMO-8400 has not yet been identified.
Clinical activity: Across all dose cohorts, 6 of 15 patients (40%) with relapsed or refractory WM had an objective response. Three responders were refractory to their last treatment, including 1 patient who was refractory to ibrutinib.
In the highest dose cohort (1.2 mg/kg twice a week):
3 of 6 patients (50%) had an objective response and two had stable disease.
The median time to first response was ~10.5 weeks.
There was improvement in bone marrow findings, hemoglobin and disease symptoms.
An exploratory analysis showed a significant correlation between change in M-protein and a change in IL-10, with decreases in IL-10 being seen in responding patients.
These data provide the first clinical evidence supporting inhibition of the TLR pathway as a potential therapeutic approach for B-cell malignancies characterized by the MYD88 L265P oncogenic mutation.
Evaluation of higher IMO-8400 dose levels is planned.
Is
general: Yes
