Early Data Show Positive Activity of Iberdomide Against Heavily Treated MM

Interim data from an ongoing Phase 1/2 clinical trial show that Celgene’s investigational therapy iberdomide (CC-220), used in combination with dexamethasone, is safe and controlled disease in nearly 90% of multiple myeloma patients who had failed multiple prior treatments.

The preliminary findings were discussed in an oral presentation, “First clinical (phase 1b/2a) study of iberdomide (CC-220; IBER), a CELMoD, in combination with dexamethasone (DEX) in patients (pts) with relapsed/refractory multiple myeloma (RRMM),” during the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Iberdomide is an orally available compound that modulates immune cell responses. It specifically targets the cereblon E3 ligase enzyme, causing degradation of factors essential to the growth of myeloma cells.d

Findings from pre-clinical studies suggest that iberdomide can stimulate strong immune responses, help overcome resistance to immunomodulatory agents such as Revlimid (lenalidomide) and Pomalyst (pomalidomide), and work well in combination with myeloma treatments such as  dexamethasone, Darzalex (daratumumab), and Velcade (bortezomib).

Iberdomide is being explored in an ongoing Phase 1b/2a trial (NCT02773030) as a potential treatment for multiple myeloma patients who have received at least two prior treatments, including an immunomodulatory agent and a proteasome inhibitor, such as Velcade.

The open-label, randomized trial is expected to include 300 patients across Europe and the U.S. In addition to testing iberdomide in combination with dexamethasone, researchers are also examining the effects of iberdomide alone and in combination with Darzalex or Velcade.

To date, 66 patients have been treated with escalating doses of iberdomide — ranging from 0.3 mg to 1.3 mg — plus dexamethasone. These patients had been previously treated with a median of five multiple myeloma treatments, which could have included a stem cell transplant, immunomodulatory agents, proteasome inhibitors, or Darzalex.

Among the 59 patients evaluable for efficacy analysis, 19 (32%) responded to treatment, including one patient with a very good partial response.

This positive anti-cancer response was also reported among patients who were refractory (had failed to respond) to treatment with Revlimid or Pomalyst, who achieved an overall response rate of 35%. Those who had failed both Darzalex and Pomalyst had an overall response rate of 29%.

“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,” Sagar Lonial, MD, chief medical officer at Winship Cancer Institute of Emory University, said in a press release.

“The early data on iberdomide in combination with dexamethasone in these heavily pretreated [multiple myeloma] patients show promising activity, and we look forward to advancing our understanding of this combination’s potential in this patient population,” he said.

Preliminary safety data suggest that iberdomide is in general safe and well-tolerated. Still, six patients (9%) discontinued treatment because of adverse events.

Most frequent serious adverse events included low numbers of neutrophils and platelets, infection, anemia, pulmonary embolism, and damage to peripheral sensory nerves.

“The preliminary clinical activity and favorable safety data observed with the combination of iberdomide and dexamethasone are encouraging,” said Alise Reicin, MD, president of global clinical development for Celgene.