Summary
The first clinical results evaluating iberdomide (CC-220) in combination with dexamethasone in patients with relapsed and refractory multiple myeloma from the ongoing phase I/II CC-220-MM-001 study were released during an oral presentation at the 2019 ASCO Annual Meeting.
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 II dose of iberdomide in combination with dexamethasone. Iberdomide is a cereblon E3 ligase modulator compound with enhanced tumoricidal and immune stimulatory effects demonstrated in preclinical studies. The phase I/II study is expected to enroll approximately 300 participants.
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Original Article
Iberdomide in Combo With Dexamethasone In Patients With Relapsed/Refractory Multiple Myeloma
Oncology Times
The first clinical results evaluating iberdomide (CC-220) in combination with dexamethasone in patients with relapsed and refractory multiple myeloma from the ongoing phase I/II CC-220-MM-001 study were released during an oral presentation at the 2019 ASCO Annual Meeting.
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 II dose of iberdomide in combination with dexamethasone. Iberdomide is a cereblon E3 ligase modulator compound with enhanced tumoricidal and immune stimulatory effects demonstrated in preclinical studies. The phase I/II study is expected to enroll approximately 300 participants.
“Nearly half a million people globally are affected by multiple myeloma. The management of patients with late relapsed or refractory multiple myeloma continues to be challenging due to the complex nature of the disease’s pathophysiology. Despite the introduction of newer agents, patients continue to experience disease relapse; therefore, new therapeutic options are needed for patients who have failed multiple prior treatments,” said Sagar Lonial, MD, Chief Medical Officer at Winship Cancer Institute of Emory University. “The early data on iberdomide in combination with dexamethasone in these heavily pretreated patients show promising activity, and we look forward to advancing our understanding of this combination’s potential in this patient population.”
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 (AE) reported included neutropenia (29%), infection (26%), anemia (24%), thrombocytopenia (12%), pulmonary embolism (1.5%) and peripheral sensory neuropathy (1.5%). Six patients (9%) 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 percent (19/59), with 29 percent (17/59) achieving a partial response and two patients achieving a very good partial response.
Patients (n=51) who were refractory to IMiD compounds, which included lenalidomide and pomalidomide, had an overall response rate of 35 percent (18/51) with 33 percent (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 (n=27) had an overall response rate of 29 percent (8/27), with 25 percent (7/27) achieving a partial response and one patient achieving a very good partial response. Maximum tolerated dose and the recommended phase II dose have not yet been determined.
The phase I/II 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.