The results included preliminary safety and efficacy data from the ongoing multicenter, open-label, dose-escalation study, which aims to determine the maximum tolerated dose and the recommended phase 2 dose of iberdomide in combination with dexamethasone.
Iberdomide is Celgene's proprietary cereblon E3 ligase modulator (CELMoD) compound with enhanced tumoricidal and immune stimulatory effects demonstrated in preclinical studies. The phase 1/2 study is expected to enroll approximately 300 participants.
As of April 2019, 66 patients at a median age of 65 received the iberdomide plus dexamethasone combination, with iberdomide being administered in 8 incremental doses ranging from 0.3 mg to 1.3 mg.
Escalating doses of iberdomide were given on days 1 through 21 in combination with dexamethasone (40 mg; 20 mg in patients older than 75) on days 1, 8, 15, and 22 of each 28-day cycle.
Patients had a median of five prior multiple myeloma treatment regimens, which could have included stem cell transplant, immunomodulatory drugs including lenalidomide and pomalidomide, proteasome inhibitors and daratumumab.
Grade 3-4 adverse events reported included neutropenia, infection, anemia, thrombocytopenia, pulmonary embolism and peripheral sensory neuropathy. Six patients discontinued treatment due to adverse events.
Of the 66 patients who received the iberdomide plus dexamethasone combination, 59 were evaluable for response. The overall response rate was 32% (19/59), with 29% (17/59) achieving a partial response and two patients achieving a very good partial response.
Patients who were refractory to IMiD compounds, which included lenalidomide and pomalidomide, had an overall response rate of 35% (18/51) with 33% (17/51) of patients achieving a partial response and one patient achieving a very good partial response.
Further, patients who were refractory to both daratumumab and pomalidomide had an overall response rate of 29%, with 25% achieving a partial response and one patient achieving a very good partial response.
Maximum tolerated dose and the recommended phase 2 dose have not yet been determined.
The phase 1/2 study is also evaluating iberdomide as monotherapy and in combination with daratumumab or bortezomib or carfilzomib. Iberdomide is investigational and has not been approved in any country.
Iberdomide is an investigational cereblon E3 ligase modulator (CELMoD) compound that induces degradation of transcription factors Aiolos and Ikaros, thereby inhibiting growth of myeloma cells in vitro.
In pre-clinical models, iberdomide has demonstrated ability to destroy tumor cells, stimulate an immune response, overcome resistance to immunomodulatory drugs, and synergize with dexamethasone, daratumumab and bortezomib.
The open-label phase 1/2 CC-220-MM-001 dose escalation study (NCT02773030) seeks to determine the maximum tolerated dose and recommended phase 2 dose of iberdomide (CC-220) as monotherapy and in combination with dexamethasone, as well as further evaluate safety and preliminary efficacy in patients with relapsed/refractory multiple myeloma.
The study consists of a dose-escalation portion (Part 1) as well as an expansion of these two cohorts at the recommended phase 2 dose to further evaluate safety and estimate preliminary efficacy (Part 2). The study also seeks to establish the maximum tolerated dose and recommended phase 2 dose of iberdomide when administered in combination with daratumumab or bortezomib or carfilzomib.
Celgene Corp., headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation.
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