Inobrodib, Pomalidomide and Dexamethasone Versus Standard Available Therapy in Relapsed or Refractory Multiple Myeloma (DOMMINO-2)

A Phase 3, Multicenter, Open-Label, Randomized Study to Evaluate Inobrodib in Combination With Pomalidomide and Dexamethasone Versus Standard Available Therapy in Patients With Relapsed or Refractory Multiple Myeloma

The main purpose of this study is to find out whether inobrodib, when given with pomalidomide and dexamethasone, works better than standard treatment for people whose multiple myeloma has come back or has not improved after previous treatment. The study will look at how long people taking part in the study ("Participants") live without their myeloma getting worse, and how many people's myeloma improves (responds) following treatment.

The study will also look at how long participants live overall, how quickly treatment works, how long the response lasts, whether very small amounts of myeloma can still be found after a good response, quality of life, side effects, and the amount of inobrodib in the blood.

Participants receive treatment in 28-day cycles. One group receives inobrodib by mouth twice a day for 4 days, followed by 3 days without inobrodib each week; pomalidomide by mouth once a day on Days 1 to 21 of each cycle; and dexamethasone once each week.

The other group receives 1 standard treatment chosen by the study doctor from the following treatment options: daratumumab, pomalidomide, and dexamethasone; elotuzumab, pomalidomide, and dexamethasone; or carfilzomib and dexamethasone. Some standard treatments are given by injection or infusion at the study site. Other medicines, such as tablets or capsules, may be taken by mouth as instructed by the study team.

Study checks include questions about symptoms and side effects, review of other medicines, physical checks, blood pressure and other vital sign checks, heart tracing tests, blood and urine tests, scans where needed, bone marrow samples, and questionnaires about symptoms and daily life. Participants in the inobrodib group will have extra blood samples to measure the amount of inobrodib in the blood. Some participants may also have extra research blood samples at selected visits.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma in Relapse; Multiple Myeloma Refractory
• Intervention / Treatment: Drug: InoPd; Drug: Investigator's choice of SAT

Detailed Description

This is a Phase 3, multicenter, open-label, randomized study to evaluate inobrodib in combination with pomalidomide and dexamethasone (InoPd) versus standard available therapy (SAT), defined as Investigator's choice of daratumumab or elotuzumab in combination with pomalidomide and dexamethasone (DPd and EPd, respectively) or carfilzomib in combination with dexamethasone (Kd), in participants with relapsed or refractory multiple myeloma (RRMM).

Participants must be 18 years or older and have received 1 to 4 prior lines of therapy only.

Approximately 450 participants will be randomized 1:1 to be treated with either InoPd (Arm A) or Investigator's choice of SAT (Arm B), which includes DPd, EPd and Kd.

Study treatment should be continued until disease progression, initiation of new anticancer therapy, unacceptable toxicity or the participant meets any criteria for withdrawal from the study.

The dual primary objectives are to compare the efficacy of InoPd with Investigator's choice of SAT in terms of progression-free survival (PFS) and objective response rate (ORR) by Blinded Independent Central Review (BICR) in participants receiving InoPd versus participants receiving SAT.

The study will use a Steering Committee, consisting of selected participating Principal Investigators, Contract Research Organization (CRO) and Sponsor representatives, and an Independent Data Monitoring Committee (IDMC), for the purposes of conduct and oversight of the study.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: CCS1477-05 Clinical Operations; Phone Number: +44 1799 531130; Email: DOMMINO-2@cellcentric.com

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33126
      • Recruiting
      • Regis Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18 years or older (or the minimum age of consent under local rules, if that is 18 or over)
• A diagnosis of multiple myeloma that has either come back (relapsed) or did not respond (refractory) after the most recent treatment
• Myeloma that can be measured using standard study tests (blood and/or urine tests)
• Between 1 and 4 previous courses (lines) of myeloma treatment, which must have included both a treatment that targets CD38 (such as daratumumab or isatuximab) and lenalidomide
• Well enough to carry out daily activities with little or no help (Eastern Cooperative Oncology Group [ECOG] performance status of 0 to 2)
• Suitable blood test results and adequate kidney and liver function
• Willingness to use highly effective contraceptive measures (if sexually active) with all sexual partners

Exclusion Criteria:

• Recent anticancer treatment before starting study treatment: any experimental medicine, chemotherapy, immunotherapy or other anticancer treatment within 14 days or 5 half-lives (whichever is shorter), or certain antibody-based treatments within longer set periods
• Previous treatment with a medicine that works in the same way as inobrodib (a p300/CBP bromodomain inhibitor)
• Myeloma that has already stopped responding to pomalidomide (pomalidomide-refractory), unless only short-term pomalidomide was used and the study doctor confirms the person still meets the study rules
• Unable to receive at least one of the standard treatment options offered in the study, or unable/unwilling to follow the requirements for at least one of those options
• Taking medicines, herbal supplements or foods (for example, strong CYP3A4 inducers or inhibitors) that would interfere with the study treatment
• Major surgery within 4 weeks before the first dose of study treatment
• A live vaccine within 4 weeks before study treatment
• A recent stem cell transplant, or ongoing transplant-related problems such as graft-versus-host disease
• Myeloma affecting the brain, spinal fluid or spinal cord, or ongoing pressure on the spinal cord
• Another active cancer (progressing or needing a change in treatment) in the last 24 months, other than multiple myeloma, apart from certain low-risk or fully treated cancers
• Serious or uncontrolled medical problems, such as uncontrolled heart, lung, liver, bleeding or diabetes conditions, uncontrolled high blood pressure, or a heart-rhythm problem (including QT prolongation)
• An active or uncontrolled infection, including certain cases of HIV, hepatitis B or hepatitis C
• Digestive problems that could stop the study medicines being swallowed or properly absorbed
• Pregnant or breastfeeding, or planning to become pregnant, father a child or donate sperm during treatment or the required post-treatment period
• Any illness or medical history that could affect safety, the ability to follow study requirements, or the interpretation of study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: InoPd; Inobrodib in combination with pomalidomide and dexamethasone	Drug: InoPd; Inobrodib in combination with pomalidomide and dexamethasone. Inobrodib 20 mg orally (PO) twice daily (b.i.d.), 4 days on/3 days off. Pomalidomide 4 mg PO once daily (o.d.) on Days 1 to 21 of each 28-day cycle. Dexamethasone 40 mg PO every week (q1w) (20 mg if >75 years old) on Days 1, 8, 15 and 22 of each 28-day cycle. Treatment will continue until progressive disease, death, unacceptable side effects, withdrawal of consent or end of study, whichever occurs first.; Other Names: Pomalyst; Dexamethasone; Imnovid; Pomalidomide; CCS1477; Inobrodib
Active Comparator: Investigator's choice of Standard Available Therapy; Investigator's choice of elotuzumab in combination with pomalidomide and dexamethasone (EPd), daratumumab in combination with pomalidomide and dexamethasone (DPd), or carfilzomib in combination with dexamethasone (Kd).	Drug: Investigator's choice of SAT; Investigator's choice of elotuzumab in combination with pomalidomide and dexamethasone (EPd), daratumumab in combination with pomalidomide and dexamethasone (DPd), or carfilzomib in combination with dexamethasone (Kd). Treatment will continue until progressive disease, death, unacceptable side effects, withdrawal of consent or end of study, whichever occurs first.; Other Names: Pomalyst; Kyprolis; Darzalex; Dexamethasone; Imnovid; Empliciti; Darzalex Faspro; Carfilzomib; Pomalidomide; Daratumumab; Elotuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) assessed by Blinded Independent Central Review (BICR)	Defined as the time from randomization until the earliest date of PD based on International Myeloma Working Group (IMWG) criteria assessed by BICR, or death due to any cause	From randomization until progressive disease or death, assessed every 28 days and followed until the final PFS analysis after approximately 330 PFS events; estimated up to approximately 38 months after the start of enrollment
Objective Response Rate (ORR) assessed by BICR	Defined as the percentage of participants with a confirmed PR or better, based on IMWG criteria assessed by BICR	From randomization until confirmed progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or the ORR data cutoff, whichever occurs first; disease response assessed every 28 days (up to 48 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Defined as the time from randomization to the date of death due to any cause	From randomization until death from any cause or the final OS analysis after approximately 329 deaths; survival status assessed every 12 weeks after disease progression or treatment discontinuation (up to 48 months)
PFS Assessed by the Investigator	Defined as the time from randomization to the earliest occurrence of progressive disease, as determined by the Investigator according to IMWG response criteria, or death from any cause.	From randomization until progressive disease or death; disease assessments performed every 28 days until confirmed progression, death, withdrawal, loss to follow-up, or end of study (up to 48 months)
ORR Assessed by the Investigator	Percentage of participants with a confirmed PR or better as determined by the Investigator according to IMWG response criteria	From randomization until confirmed progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
Minimal Residual Disease (MRD) Negativity Rate	Percentage of participants achieving minimal residual disease (MRD) negativity at CR or better, measured by next-generation sequencing	At confirmed CR or better; if MRD negativity is not demonstrated at CR, reassessed within 3 to 6 months after confirmation of CR or better (up to 48 months)
Duration of Response (DoR) Assessed by BICR	Defined, among participants with a confirmed PR or better, as the time from the first documented response to progressive disease determined by BICR or death from any cause, whichever occurs first	From the first documented confirmed response until progressive disease or death; assessed every 28 days until progression or end of study (up to 48 months)
DoR Assessed by the Investigator	Defined, among participants with a confirmed PR or better, as the time from the first documented response to progressive disease determined by the Investigator or death from any cause, whichever occurs first	From the first documented confirmed response until progressive disease or death; assessed every 28 days until progression or end of study (up to 48 months)
Time to Response (TTR) Assessed by BICR	Defined, among participants achieving a confirmed response, as the time from randomization to the first documented PR or better determined by BICR according to IMWG response criteria	From randomization to the first documented confirmed response; assessed every 28 days (up to 48 months)
TTR Assessed by the Investigator	Defined, among participants achieving a confirmed response, as the time from randomization to the first documented PR or better determined by the Investigator according to IMWG response criteria	From randomization to the first documented confirmed response; assessed every 28 days (up to 48 months)
Very Good Partial Response (VGPR) or Better Rate Assessed by BICR	Percentage of participants with a confirmed VGPR or better-VGPR, CR, or sCR-as determined by BICR according to IMWG response criteria	From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
VGPR or Better Rate Assessed by the Investigator	Percentage of participants with a confirmed VGPR or better as determined by the Investigator according to IMWG response criteria	From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
Complete Response (CR) or Better Rate Assessed by BICR	Percentage of participants with a confirmed CR or sCR as determined by BICR according to IMWG response criteria	From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
CR or Better Rate Assessed by the Investigator	Percentage of participants with a confirmed CR or sCR as determined by the Investigator according to IMWG response criteria	From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
Change From Baseline in EORTC QLQ-C30 Scores	Defined as the change from baseline in functional, symptom, and global health status/quality-of-life scores from the EORTC QLQ-C30 questionnaire	Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
Change From Baseline in EORTC QLQ-MY20 Disease Symptoms Score	Defined as the change from baseline in the Disease Symptoms domain score of the EORTC QLQ-MY20 questionnaire	Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
Change From Baseline in EQ-5D-5L Health Status	Defined as the change from baseline in the EQ-5D-5L health-state index and visual analogue scale scores	Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
Treatment Side-Effect Bother Assessed by FACT-GP5	Defined as participants' responses to FACT-GP5 regarding how bothered they were by treatment side effects during the previous 7 days	Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
Symptomatic Adverse Events Assessed by PRO-CTCAE	Defined as participant-reported frequency, severity, or interference of selected symptomatic adverse events using the PRO-CTCAE	Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
Participants With Treatment-Emergent Adverse Events	Defined as the number and percentage of participants with adverse events that begin or worsen after the first dose of study treatment	Assessed from the first dose of study treatment through 28 days after the last dose (up to 48 months)
Change From Baseline in Electrocardiogram Parameters	Defined as changes from baseline and clinically significant abnormalities in protocol-specified 12-lead electrocardiogram parameters	Assessed at baseline and protocol-specified visits during treatment through the 28-day post-treatment follow-up visit (up to 48 months)
Change From Baseline in Vital Signs	Defined as changes from baseline and clinically significant abnormalities in protocol-specified vital-sign measurements	Assessed at baseline and protocol-specified visits during treatment through the 28-day post-treatment follow-up visit (up to 48 months)
Participants With Laboratory Abnormalities	Defined as the number and percentage of participants with hematology, chemistry, or other protocol-specified laboratory abnormalities	Assessed at baseline and protocol-specified visits during treatment through the 28-day post-treatment follow-up visit (up to 48 months)
Plasma Concentrations of Inobrodib	Defined as the measured plasma concentrations of inobrodib and, where analyzed, its primary metabolite CCS1532	Assessed at protocol-specified predose and postdose time points during treatment (up to 48 months)

Collaborators and Investigators

• Sponsor: CellCentric Ltd.
• Investigators: Study Director: Study Director, CellCentric Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2031

Study Registration Dates

• First Submitted: August 13, 2026
• First Submitted That Met QC Criteria: August 17, 2026
• First Posted (Actual): August 19, 2026

Study Record Updates

• Last Update Posted (Actual): August 19, 2026
• Last Update Submitted That Met QC Criteria: August 17, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Pomalidomide; Dexamethasone; Imnovid; Pomalyst; Inobrodib; p300-CBP Transcription Factors; CCS1477
• Additional Relevant MeSH Terms: Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Dexamethasone; carfilzomib; pomalidomide; elotuzumab; daratumumab; CCS1477
• Other Study ID Numbers: CCS1477-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The final clinical study report will be provided to the Investigators. The Sponsor will publicly disclose study results through posting on ClinicalTrials.gov and any other applicable public registries in accordance with local regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No