Pivotal Trial Initiated for Inobrodib Combination in R/R Multiple Myeloma

The first patient has been treated in DOMMINO-1 (NCT07096778), a pivotal phase 2 clinical trial evaluating inobrodib (CCS1477) in combination with pomalidomide (Pomalyst) and dexamethasone (InoPd) in heavily pretreated patients with relapsed or refractory multiple myeloma (R/R MM), according to a news release from CellCentric.¹

The trial began treating patients at The Royal Marsden NHS Foundation Trust in London, with additional sites now open across the United Kingdom and the United States. The single-arm, open-label study aims to enroll 100 adult patients and represents a registration-enabling step for this novel all-oral regimen following a successful dose-optimization trial.

“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,” said Charlotte Pawlyn, MD, Honorary Consultant Hematologist at The Royal Marsden NHS Foundation Trust, Group Leader in Myeloma Biology and Therapeutics at The Institute of Cancer Research, London, and a principal investigator for the DOMMINO‑1 study, in the news release.

Background: Inobrodib and the p300/CBP Pathway

Inobrodib is a first-in-class, orally bioavailable inhibitor of p300 and CREB-binding protein, which play a central role in the transcriptional programs that sustain myeloma cell survival, including those driven by IRF4 and MYC. The compound has now been evaluated in more than 450 patients.^1,2

Data from a phase 1/2 trial (NCT04068597) demonstrated that inobrodib was active across hematologic malignancies and selected solid tumors.² Early clinical signals showed evidence of single-agent activity in myeloma, and the tolerability profile at the 20 mg dose was noted to be consistent with that of the pomalidomide-dexamethasone backbone when used in combination, vital for a drug intended for use in frail, heavily pretreated patients.³

Trial Design and Patient Population

DOMMINO-1 targets a patient population with significant unmet need: individuals who have are refractory to at least 1 proteasome inhibitor, 1 anti-CD38 monoclonal antibody, and pomalidomide.⁴ Patients will receive 20 mg inobrodib orally twice daily for 4 days on, 3 days off, with 4 mg pomalidomide from day 1 to 21 and 40 mg dexamethasone on days 1, 8, 15, and 22 of each 28-day cycle.

The primary end point is overall response rate (ORR) by independent review committee, with secondary end points including progression-free survival, overall survival, and duration of response. The inobrodib dose of 20 mg was selected based on recent dose-optimization work conducted under the FDA's Project Optimus framework and shared with regulatory agencies including the FDA.¹

Previous Dose-Finding and Efficacy Data

Phase 1/2 data presented at the American Society of Hematology Annual Meeting in 2025 informed the design of DOMMINO-1.³ A cohort of patients including some who were refractory to prior pomalidomide were randomly assigned to receive 20 mg, 30 mg, or 40 mg of inobrodib with pomalidomide and dexamethasone. Among 44 patients at the reported data cutoff, the ORR was 69% in the 20-mg cohort. Emerging ORRs of 54% and 33% were reported in the 30-mg and 40-mg cohorts, and higher rates of dose interruption and deescalation were reported as well.

In patients who had received at least 5 prior lines of therapy including B-cell maturation antigen–directed therapy and/or bispecific T-cell engager whose disease failed to respond to pomalidomide, InoPd demonstrated an ORR of 60% in the 20-mg group and 75% in the 30-mg group, significantly higher than historical comparators in comparable populations. These results, drawn from the randomized dose-optimization study, provided the rationale for advancing the 20-mg dose into the current pivotal trial.

The safety profile was favorable in the 20-mg group and was reported to be in line with outcomes with pomalidomide/dexamethasone alone in less pretreated patients. In all treated patients, the most common adverse events were cytopenias and fatigue, with the most frequently grade 3 or 4 toxicities being thrombocytopenia in 36, neutropenia in 34%, and anemia in 20%.

Clinical and Practical Implications

The all-oral nature of this regimen offers an advantage in access; a large proportion of the patients were able to receive this regimen in the community setting. “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,” Nisha Joseph, MD, associate professor in the Department of Hematology and Medical Oncology, Emory University School of Medicine in Atlanta and DOMMINO-1 principal investigator at the first US trial site, said in the news release.¹

Inobrodib is also under investigation in combination with the B-cell maturation antigen (BCMA)-directed bispecific antibodies elranatamab (Elrexfio) and teclistamab (Tecvayli), and a maintenance-setting proof-of-concept study is ongoing.

Enrollment for DOMMINO-1 is ongoing at sites in the UK and US. “Inobrodib represents a novel mechanism through inhibition of p300/CBP and has demonstrated the ability to be used in combination with established therapies. We look forward to further evaluating InoPd in this trial,” Pawlyn stated.

REFERENCES

1. CellCentric initiates DOMMINO-1, a pivotal phase 2 clinical trial of inobrodib in combination with pomalidomide and dexamethasone (InoPd) in relapsed or refractory multiple myeloma. News release. CellCentric. March 31, 2026. Accessed March 31, 2026. https://tinyurl.com/mrxmda4f

2. Searle E, Cavet J, Knapper S, et al. P863: an open-label phase I/IIa study to evaluate the safety and efficacy of CCS1477 as monotherapy and in combination with pomalidomide/dexamethasone in relapsed/refractory multiple myeloma. Hemasphere. 2023;7(Suppl ):e54143bc. doi:10.1097/01.HS9.0000970356.54143.bc

3. CellCentric Presents Positive Phase 2 Dose Optimization Data for Inobrodib in Multiple Myeloma at ASH Annual Meeting. News release. December 7, 2025. Accessed March 31, 2026. https://tinyurl.com/6xrc7n7t

4. Inobrodib, Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma (DoMMino-1). ClinicalTrials.gov. Updated February 6, 2026. Accessed March 31, 2026. https://clinicaltrials.gov/study/NCT07096778