Hope for multiple myeloma patients who have exhausted standard-of-care therapies

UK-based biotech, CellCentric which spun out of Cambridge University has yesterday (December 11) announced new clinical data for the drug at the American Society for Hematology (ASH) in San Diego.

The results follow a recent publication in the Cancer Cell journal, which describes the novel mechanism of action of inobrodib, a first in a new class of drug – an oral agent.  The drug disrupts the action of p300/CBP at regulatory elements controlling key cancer genes.

Inobrodib impacts the expression of IRF4 and MYC, two potent oncogenes that drive multiple myeloma. The mechanism is clearly differentiated from that of other commonly used drugs, and it has also been proven to be synergistic to agents such as the IMiDs.  As now shown clinically, patients refractory to pomalidomide become responsive to inobrodib combined with pom + dex.

“We are pleased that clinical activity of this combination is so encouraging in last-line patients, confirming the potential of this new approach,” said Tomasz Knurowski, chief medical officer at CellCentric.

“Further evaluation is underway, but there are clear signs that targeting p300/CBP to treat haematological malignancies, including myeloma, has the potential to address unmet medical need.”

The data has been derived from heavily pre-treated patients, who are mostly triple-class refractory (when the disease does not respond to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies), with a median of five lines of prior therapy who have been taking part in a multi-center phase 1/2a clinical​ trial.  

Data were shared at ASH from two combination cohorts at doses of inobrodib at 25mg or 35mg twice daily on a four days on / three days off intermittent schedule, with standard dosing of pom + dex in 28-day cycles.

The results showed inobrodib has a manageable safety profile.  All patients demonstrated some signs of clinical activity, with rapid responses - 72% greater than or the same as MR by IMWG criteria in both cohorts and 67% ORR in the 35mg cohort.  A significant number of patients across both dosing cohorts remain on treatment after six months.

CellCentric has previously reported initial monotherapy tolerability and efficacy data, at ASH 2022.

Emma Searle, consultant haematologist at The Christie NHS Foundation Trust, who has overseen the care of many of the patients on the clinical trial, added: “The results show promising efficacy data in relapsing-remitting multiple myeloma patients who have exhausted standard-of-care therapies, both as a monotherapy and in combination with pom + dex. Further trials continue to refine dosing and expand the cohort.”

Multiple myeloma, also known as myeloma, is a type of bone marrow cancer. Bone marrow is the spongy tissue at the center of some bones that produces the body's blood cells.

It is called multiple myeloma as the cancer often affects several areas of the body, such as the spine, skull, pelvis and ribs.