Furlong, Maggie

TPS8057 Background: Multiple myeloma (MM) is the second most prevalent blood cancer, representing approximately 1% of all cancers. Although overall survival has improved in recent years due to new approved agents, the vast majority of MM patients (pts) ultimately stop responding to treatment. Moreover, about a quarter of MM pts characterized as “high risk” experience limited benefit from existing treatments. Seminal genomic sequencing research efforts, such as the MMRF CoMMpass study, have highlighted that a large number of MM cases harbor potentially actionable oncogenic molecular alterations and published reports on small numbers of cases suggest that Precision Medicine (PM) interventions clinically targeting such actionable drivers may benefit MM pts. These results suggest that PM approaches in MM are possible and should be further studied clinically. To that end, we have launched MyDRUG, a master protocol aimed at developing new myeloma regimens based on individual pt’s genomics. Methods: This study is a Phase I-II, multicenter master protocol in functional high risk MM patients (i.e patients having progressed from baseline treatment within 18 months without maintenance or 3 years on maintenance) with 1-3 prior lines of therapy. Patients are screened for actionable genomic alterations on the CLIA-grade MI-ONCOSEQ platform. Patients with actionable alterations are assigned to the appropriate targeted agent used in combination with a backbone regimen ixazomib, pomalidomide and dexamethasone (IPd), whereas patients without such alterations go on an immune arm (see Table). Inclusion criteria include measurable disease (as measured by M-protein and FLC) and acceptable hematologic and metabolic functions. A maximum of 12 evaluable pts will be accrued onto the phase I portion of each arm and an additional 21 evaluable phase II pts will be accrued onto each arm for a total of 27 evaluable pts at the MTD combination dose. The primary objective of the study is to evaluate ORR per IMWG consensus criteria. Secondary objectives are to assess adverse events (AEs), progression-free survival, and overall survival (OS). Experimental correlative aims include assessing molecular or clonal response, molecular and immune signatures of resistance/response, MRD. Clinical trial information: NCT03732703. [Table: see text]