CellCentric's Inobrodib Shows 60-75% Response Rates in Heavily Pretreated Multiple Myeloma Patients
核心洞察
CellCentric (搜索) reported positive Phase 2 dose optimization data for inobrodib combined with pomalidomide and dexamethasone, showing 60-75% response rates in heavily pretreated relapsed/refractory multiple myeloma patients.
The oral p300/CBP (搜索) inhibitor demonstrated at least two-fold higher clinical efficacy compared to real-world data for patients previously exposed to BCMA (搜索)-targeted therapies or bispecifics.
The treatment showed a favorable safety profile with tolerability comparable to pomalidomide-dexamethasone alone, positioning it as a potential first-in-class therapy for patients who cannot tolerate or have relapsed on bispecific treatments.
CellCentric (搜索) announced compelling Phase 2 dose optimization results for inobrodib, a first-in-class oral p300/CBP (搜索) inhibitor, in combination with pomalidomide and dexamethasone (InoPd) for heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients. The data, presented at the American Society of Hematology (ASH) annual meeting, demonstrated strong clinical efficacy and a tolerable safety profile in patients with high-risk disease and prior exposure to T-cell engagers and BCMA (搜索)-targeted therapies.
Strong Efficacy in Challenging Patient Population
The Phase 2 dose optimization study randomized participants to three dose levels of inobrodib (20mg, 30mg, 40mg on an intermittent schedule) combined with standard dosing of 4mg pomalidomide and 20-40mg dexamethasone depending on age. Among 44 evaluable patients, the emerging objective response rate (ORR) reached 69% for patients in the 20mg cohort.
Particularly notable were the results in heavily pretreated patients with a median of five prior lines of therapy who were pomalidomide-refractory and had previously failed BCMA (搜索) and/or T-cell engager therapy. In this challenging population, deep and durable ORRs of 60% at 20mg and 75% at 30mg were observed.
"This represents at least a two-fold increase against currently available MM therapies after BCMA (搜索)/TCE agents, where real-world ORR rates are 25-30% in a similar patient population," according to the company's data presentation.
Dose-Dependent Response and Safety Profile
Early analyses revealed dose-dependent tolerability patterns, with more dose interruptions and de-escalations at higher doses. The emerging ORRs were 54% for the 30mg cohort and 33% for the 40mg cohort. Across all cohorts, responses continued to deepen and lengthen over time.
The safety profile proved favorable, with the tolerability of the 20mg inobrodib triplet comparable to previously reported datasets of pomalidomide-dexamethasone alone in less heavily pretreated patients. The most commonly reported treatment-emergent adverse events of any grade were cytopenias and fatigue. Grade 3/4 adverse events included thrombocytopenia (36%), neutropenia (34%), and anemia (20%).
Addressing Unmet Medical Need
"While bispecifics in particular have been transformative in the treatment of multiple myeloma, in later lines of therapy almost half of patients ultimately relapse and around one-third do not respond at all," said Will West, Chief Executive Officer of CellCentric (搜索). "InoPd offers a completely novel mechanism of action as an oral regimen that can be well tolerated."
The oral small molecule drug targets p300/CBP (搜索) bromodomains to lower expression of key cancer drivers, including MYC (搜索) and IRF4 (搜索). Inobrodib has been evaluated in over 450 patients to date across hematologic malignancies and solid tumors.
Clinical Development and Regulatory Path
Following recent discussions with the FDA, CellCentric (搜索) plans to initiate pivotal registration studies next year. The company maintains all development and commercial rights to inobrodib and is exploring the drug in combination with elranatamab and teclistamab, as well as investigating proof of concept in a maintenance setting.
"Coupled with the observed efficacy responses, many of which we expect will reach complete response and MRD-negative disease status as data matures, InoPd could have substantial impact as a first-in-class treatment for the multiple myeloma patient community," said Tomasz Knurowski, M.D., Chief Medical Officer of CellCentric (搜索).
The oral administration offers practical advantages for the more than 70% of multiple myeloma patients treated in community settings, designed for home use without intensive monitoring requirements. This ease of administration could reduce healthcare system burden relative to more complex therapies while broadening access for patients who cannot tolerate other treatments.