The stairway near the entrance of Chicago’s McCormick Place during the 2019 ASCO meeting

One of a new class of drugs being developed for multiple myeloma has shown a high response rate in patients who have received already failed on the so-called “backbone” treatments used for the disease, according to data presented at the recent American Society of Clinical Oncology meeting.

New York-based Bristol-Myers Squibb showed data from the Phase I dose-escalation study of CC-92480, a cereblon E3 ligase modulator, or CELMoD drug, plus the steroid dexamethasone, in patients with relapsed or refractory multiple myeloma.

Data from the study showed that among 76 patients evaluable for efficacy, the overall response rate was 21.1%. Among the 11 patients receiving the drug according to the dosing and schedule recommended for Phase II development – 1mg per day for treatment cycles of 28 days, wherein patients received the drug for three weeks, followed by no drug for one week – the ORR was 54.5%, with 27.3% of patients achieve a very good partial response or complete response. Most of the severe or worse side effects were hematological toxicities, as well as fatigue.

Patients in the study tended to be heavily pretreated – including half who were refractory to an immunomodulating agent like Revlimid, a proteasome inhibitor and an anti-CD38 monoclonal antibody, collectively considered the backbone of myeloma treatment. BMS acquired all three of the immunomodulators, or IMiDs, used to treat myeloma – Revlimid, Pomalyst (pomalidomide) and Thalomid (thalidomide) when it acquired Celgene last year for $74 billion.

Dr. Paul Richardson, a professor of medicine at Harvard Medical School who presented the CC-92480 data, said in a phone interview that the early efficacy signal is in part due to CELMoDs being designed for rapid protein degradation.

“It’s really designed and built to lead to highly efficient protein degradation, and that in turn drives dramatic effects,” Richardson said.

Noting that CELMoDs are distinct agents from immunomodulators, he pointed out that where Revlimid’s maximum degradation point takes 35 minutes and Pomalyst’s took 20, CC-92480 took only five minutes. He noted that the drug is not just another immunomodulator, but a distinct agent.

“The analogy being used is that it’s CAR-T in a pill,” Richardson said, a comparison that alludes to the dramatic efficacy seen from CAR-T cell therapies. “That’s obviously a ha-ha, but it’s not an inappropriate metaphor.”

Photo: Alaric DeArment, MedCity News

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