Recent reports have identified a specific oncogenic mutation L265P of the MYD88 gene in approximately 90% of the patients with Waldenström's macroglobulinemia. MYD88 is a key linker protein in the signaling pathway of Toll Like Receptors (TLRs) 7, 8, and 9, and IMO-8400 is an oligonucleotide specifically designed to inhibit TLRs 7,8, and 9. The scientific hypothesis for use of IMO-8400 to treat patients with Waldenström's macroglobulinemia depends on the inhibition of mutant MYD88 signaling in the TLR pathway, thereby interrupting the proliferation of cell populations responsible for the propagation of the disease.
Name: IMO-8400
Description: Safety and tolerability of IMO-8400 in patients with Waldenstrom's Macroglobulinemia: Assessment of adverse events
Measure: Safety and Tolerability of IMO-8400 in Patients With Waldenstrom's Macroglobulinemia Time: Up to 24 weeksDescription: Best Overall Response using criteria from the VIth International Workshop in Waldenstrom's Macroglobulinemia
Measure: Best Overall Response Time: Up to 24 weeksDescription: To identify an appropriate dose of IMO-8400 for further clinical evaluation via evaluation of DLT at each dose level
Measure: Identify the Number of Patients Experiencing DLTs at Each Dose Level Time: 28 daysDescription: Pharmacokinetics of escalating dose levels of IMO 8400 administered by SC injection - Cmax.
Measure: Pharmacokinetics of Escalating Dose Levels of IMO 8400 Administered by SC Injection - Cmax. Time: Cycle 1 Week 1 Day 1: Samples were obtained pre-dose (within 1 hr prior to injection) and post-dose at 1 hr (+/-5 min), 2 hrs (+/-10 min) and 4 hrs (+/-15 min)Description: Pharmacokinetics of escalating dose levels of IMO 8400 administered by SC injection - AUC0-t (hr*ng/mL) .
Measure: Pharmacokinetics of Escalating Dose Levels of IMO 8400 Administered by SC Injection - AUC0-t (hr*ng/mL) Time: Cycle 1 Week 1 Day 1: Samples were obtained pre-dose (within 1 hr prior to injection) and post-dose at 1 hr (+/-5 min), 2 hrs (+/-10 min) and 4 hrs (+/-15 min)Allocation: N/A
Single Group Assignment
There is one SNP
Phase 1/2 Dose Escalation Study in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia Recent reports have identified a specific oncogenic mutation L265P of the MYD88 gene in approximately 90% of the patients with Waldenström's macroglobulinemia. --- L265P ---