FDA Awards Orphan Drug Designation to Inobrodib for Multiple Myeloma

The FDA has granted orphan drug designation to inobrodib (CCS1477) for use as a potential therapeutic option in patients with multiple myeloma, according to an announcement from the biotechnology company CellCentric.¹

The investigative agent binds to a specific portion of the p300 and CBP proteins and is designed to be highly selective. Through its mechanism of action, inobrodib results in decreased IRF4 and MYC expression as well as the androgen receptor and its variants. Notably, the agent is administered orally and can be taken at home without the need for intensive monitoring.

The safety, tolerability, and biologic activity of inobrodib is under investigation in patients with multiple myeloma, non-Hodgkin lymphoma (NHL), acute myeloid leukemia (AML), and high-risk myelodysplastic syndrome (MDS) as part of an ongoing phase 1/2 study (NCT04068597).²

“Orphan drug designation for inobrodib is an important milestone in our journey to develop an additional therapeutic option for patients with multiple myeloma,” Tomasz Knurowski, chief medical officer of CellCentric, stated in a press release.¹ “We look forward to providing an update on our clinical data by the end of the year, which will help inform the next stage of development of inobrodib.”

The early-phase study is recruiting patients with confirmed relapsed or refractory hematologic malignancies who received prior standard treatment, have an ECOG performance status ranging from 0 to 2, and acceptable organ function.²

Patients who received any chemotherapy, investigational drug, or other anticancer agents within 2 weeks of the first study dose will be excluded, as will those who have undergone a major surgery or who experienced substantial traumatic injury in the 4 weeks prior to study treatment initiation. Other exclusion criteria are having received CYP3A4 inhibitors or substrates or CYP3A4 inducers within 2 and 4 weeks of treatment initiation, respectively.

Several interventions are being explored in multiple arms of the trial. In the dose-escalation phase of the trial, inobrodib monotherapy is being explored in an arm of patients with multiple myeloma as well as an arm of patients with AML or high-risk MDS. In the expansion phase, single-agent inobrodib is being assessed in patients with peripheral T-cell lymphoma. In the expansion and dose-finding phase, inobrodib is being evaluated in the following arms:

• as a monotherapy and in combination with pomalidomide (Pomalyst) and dexamethasone in patients with multiple myeloma
• as a monotherapy, in combination with azacitidine, and in combination with azacitidine and venetoclax (Venclexta) in patients with AML
• as a monotherapy, in combination with azacitidine, and in combination with azacitidine and venetoclax in patients with higher-risk MDS

The primary end points of the trial are incidence of treatment-related toxicities and laboratory abnormalities. Secondary end points include response rate, duration of response, area under the plasma concentration-time curve from time 0 to time of last measurable concentration of the drug, and maximum plasma concentration observed with the drug.

CellCentric shared that data from the expansion cohort will be shared at the 2023 ASH Annual Meeting, specifically information related to inobrodib as a single agent and in combination with pomalidomide and dexamethasone in patients with multiple myeloma.¹

Previously, in June 2023, the FDA granted fast track designation to inobrodib for use in patients with relapsed or refractory multiple myeloma.³

Data presented at the 2022 ASH Annual Meeting showed that of the 7 patients with relapsed/refractory multiple myeloma who received inobrodib at the recommended phase 2 dose, 6 experienced reduction or stabilization of serum-free light chains.⁴

One unconfirmed complete response was observed in a patient, and this became a confirmed very good partial response that proved to be durable. Another patient had a confirmed partial response (PR), and a third patient had an unconfirmed PR. All 3 of these patients received treatment for at least 8 months. Regarding safety, the agent was found to be well tolerated with mild or moderate on-target adverse effects observed.

References

1. CellCentric granted FDA orphan drug designation for inobrodib (CCS1477) for the treatment of multiple myeloma. News release. CellCentric. June 29, 2023. Accessed July 6, 2023. https://www.cellcentric.com/press-release/cellcentric-granted-fda-orphan-drug-designation-for-inobrodib-ccs1477-for-the-treatment-of-multiple-myeloma/
2. Study to evaluate CCS1477 in haematological malignancies. ClinicalTrials.gov. Updated April 27, 2023. Accessed July 6, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04068597
3. CellCentric receives FDA fast track designation for inobrodib for the treatment of patients with relapsed refractory multiple myeloma. News release. CellCentric. June 13, 2023. Accessed July 6, 2023. https://www.cellcentric.com/press-release/cellcentric-receives-fda-fast-track-designation-for-inobrodib-for-the-treatment-of-patients-with-relapsed-refractory-multiple-myeloma/
4. CellCentric presents early haem clinical data at ASH. News release. CellCentric. December 11, 2022. Accessed July 6, 2023. https://www.cellcentric.com/press-release/cellcentric-presents-early-clinical-data-at-ash/