CellCentric Launches Pivotal Phase 2 Trial of Inobrodib Combination for Relapsed Multiple Myeloma
核心洞察
CellCentric (搜索) has initiated DOMMINO-1, a pivotal Phase 2 trial evaluating inobrodib 20 mg combined with pomalidomide and dexamethasone in heavily pretreated relapsed or refractory multiple myeloma patients.
The combination previously demonstrated a 60% objective response rate and response rates at least 2x greater than alternatives in pomalidomide-refractory patients following bispecific or anti-BCMA (搜索) therapy.
The open-label, single-arm study will enroll 100 patients across UK and US sites, targeting patients who have exhausted multiple treatment options including bispecific antibodies.
CellCentric (搜索) has dosed the first patient in DOMMINO-1, a pivotal Phase 2 clinical trial evaluating inobrodib 20 mg in combination with pomalidomide and dexamethasone (InoPd) for heavily pretreated patients with relapsed or refractory multiple myeloma (RRMM). The first patient was dosed at The Royal Marsden NHS Foundation Trust in London, with additional sites now open in the UK and United States.
The combination therapy has shown promising early results, with inobrodib 20 mg plus pomalidomide and dexamethasone demonstrating a 60% objective response rate and response rates at least 2x greater than alternatives for heavily pretreated pomalidomide-refractory patients following bispecific T cell engager or anti-BCMA (搜索) therapy.
Novel Mechanism Addresses Treatment-Resistant Disease
"Inobrodib 20 mg with pom + dex has demonstrated encouraging clinical activity, including a 60% objective response rate, and a tolerability profile consistent with pom-dex alone," said Naseer Qayum M.D., Ph.D., Chief Strategy Officer and Head of R&D at CellCentric (搜索). "Patients who are refractory to pomalidomide and have progressed following bispecifics or other BCMA (搜索)-directed therapies have very limited options. We believe InoPd may deliver a transformative all-oral treatment for RRMM patients."
Inobrodib represents a first-in-class, oral p300/CBP (搜索) inhibitor that offers a novel mechanism of action complementary to existing treatments. Charlotte Pawlyn, M.D., Honorary Consultant Hematologist at The Royal Marsden NHS Foundation Trust and Principal Investigator for the DOMMINO-1 study, emphasized the urgent need for new treatment options: "Advances in multiple myeloma treatment, including bispecific antibodies, have improved patient outcomes. However, many people ultimately relapse or become refractory to these therapies, and new treatment options are urgently needed."
Trial Design and Patient Population
DOMMINO-1 is a Phase 2 open-label, single-arm study enrolling 100 adult patients across clinical sites in the UK and U.S. (NCT07096778). The trial is designed to assess the safety and efficacy of InoPd, with participants receiving inobrodib at a 20 mg dose, as supported by recent dose-optimization work (Project Optimus) shared with the U.S. Food and Drug Administration (FDA) and other regulatory agencies.
The primary endpoint is overall response rate, with secondary endpoints including progression-free survival, overall survival and duration of response. Eligible participants must have previously received a bispecific antibody and be refractory to at least one proteasome inhibitor, one anti-CD38 (搜索) monoclonal antibody and pomalidomide.
Practical Benefits for Community Treatment
The all-oral nature of the regimen could provide significant practical advantages for patients and healthcare systems. "More than 70% of patients are treated in the community setting, and an all-oral regimen may facilitate and expand access for those living with this disease, as well as their caregivers and healthcare providers," said Nisha Joseph, M.D., Associate Professor at Emory University School of Medicine and DOMMINO-1 principal investigator at the first U.S. trial site.
Broader Development Program
Inobrodib has been evaluated in over 450 patients to date, with clinical activity observed in both hematologic malignancies and solid tumors. The drug is delivered as an oral capsule designed for home use without intensive monitoring requirements. Beyond the InoPd combination, inobrodib is being explored in combination with bispecific therapies elranatamab and teclistamab, with proof of concept studies also underway in maintenance settings.
The U.S. FDA has previously granted Fast Track and Orphan Drug Designations to inobrodib for RRMM. CellCentric (搜索) maintains all development and commercial rights to inobrodib and continues to expand the program in combination with other agents.