A Safety, PK and Efficacy Study of CC-92480 Monotherapy and in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)

NCT03374085 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: CC-92480-MM-001U1111-1205-36502017-001236-19
• Study Type: interventional
• Target: 200
• Locations: 11 countries
• Sites: 54

Brief Summary

This is an open-label, multi-center, international, Phase 1/2 study to assess the safety, PK and efficacy of CC-92480 monotherapy and in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma (RRMM). All eligible subjects must be previously treated with at least 3 prior regimens including lenalidomide, pomalidomide, a proteasome inhibitor and an anti-CD38 antibody and be refractory to their last line of therapy.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Safety; Efficacy; CC-92480; Relapsed; Refractory

Outcome Measures

Primary Outcomes (9)

• Adverse Events (AEs)

  Number of participants with AEs to CC-92480 and/or dexamethasone (Type, frequency, seriousness, severity and relationship of AEs to CC-92480 and dexamethasone; changes from baseline in clinically-relevant physical findings, vital signs, selected laboratory analytes, ECGs).

  From enrollment until at least 28 days after completion of study treatment

• Pharmacokinetics- AUC

  Area under the plasma concentration-time curve

  Up to approximately 28 days

• Pharmacokinetics- Cmax

  Maximal plasma concentration

  Up to approximately 28 days

• Pharmacokinetics- Tmax

  Time to Cmax

  Up to approximately 28 days

• Pharmacokinetics- t1/2

  Terminal-phase elimination half-life

  Up to approximately 28 days

• Pharmacokinetics- CL/F

  Apparent total clearance of the drug from plasma after oral administration

  Up to approximately 28 days

• Pharmacokinetics- Vz/F

  Apparent volume of distribution during terminal phase after non-intravenous administration

  Up to approximately 28 days

• Maximum tolerated dose (MTD)

  The highest dose of CC-92480 in combination with dexamethasone associated acceptable safety and tolerability.

  Up to approximately 28 days

• Overall Response Rate (ORR)

  Overall response rate (ORR) of CC-92480 in combination with dexamethasone in Part 2

  Up to approximately 3 years

Secondary Outcomes (6)

• Overall response rate (ORR)

  Up to approximately 3 years

• Time to response (TTR)

  Up to approximately 3 years

• Duration of response (DOR)

  Up to approximately 3 years

• Progression free survival

  Up to approximately 3 years

• Overall survival (OS)

  Up to approximately 3 years

Study Arms (2)

Administration of CC-92480 in combination with dexamethasone

EXPERIMENTAL

Part 1: Escalating doses of CC-92480 plus a fixed dose of dexamethasone Part 2: RP2D of CC-92480 in combination with dexamethasone

Drug: CC-92480; Drug: Dexamethasone

Administration of CC-92480 monotherapy

EXPERIMENTAL

Escalating doses of CC-92480 Monotherapy administered according to different dosing schedules

Drug: CC-92480

Interventions

CC-92480 DRUG

CC-92480

Also known as: BMS-986348, mezigdomide

Administration of CC-92480 in combination with dexamethasone; Administration of CC-92480 monotherapy

Dexamethasone DRUG

Dexamethasone

Administration of CC-92480 in combination with dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• Subjects must have a documented diagnosis of MM and measurable disease at enrollment. Measurable disease is defined as:
• M-protein quantities ≥ 0.5 g/dL by sPEP or
• ≥ 200 mg/24 hour urine collection by uPEP or
• Serum FLC levels \> 100 mg/L (milligrams/liter) involved light chain and an abnormal kappa/lambda (κ/λ) ratio in subjects without measurable serum or urine M-protein or
• For subjects with immunoglobulin class A (IgA), myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥ 0.50 g/dL.
• All subjects must have:
• Received at least 3 prior anti-myeloma regimens including at least 2 consecutive cycles of lenalidomide, pomalidomide, a proteasome inhibitor, a glucocorticoid and a CD38 antibody (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered one regimen).
• Documented disease progression on or within 60 days from the last dose of their last myeloma therapy
• Subjects who had CAR-T therapy as their last myeloma therapy are eligible as long as they have documented disease progression following CAR-T therapy.
• In addition to criteria above (a and b), subjects enrolled in Part 2 must have disease refractory to an immunomodulatory agent (lenalidomide and/or pomalidomide), a glucocorticoid, a proteasome inhibitor, and a CD38 antibody. Refractory is defined as disease that is nonresponsive on therapy (failure to achieve minimal response or development of progressive disease), or progresses within 60 days of last dose.
• Subjects must have the following laboratory values:

You may not qualify if:

• Subject has a significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject has non-secretory multiple myeloma.
• Subject has refractory primary multiple myeloma (ie, no history of at least a minor response to a prior treatment regimen).
• Subject has plasma cell leukemia or active leptomeningeal myelomatosis.
• Subject has documented, systemic light chain amyloidosis or Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS) Syndrome.
• Subject has immunoglobulin class M (IgM) myeloma.
• Part 1: Subject has a history of allogeneic bone marrow transplantation. Part 2: Subject has a history of allogeneic bone marrow transplantation within 6 months prior to first dose. Subject should not have ongoing graft-versus-host disease (GVHD) requiring systemic immunosuppression.
• Subject is undergoing dialysis.
• Subjects with peripheral neuropathy ≥ Grade 2.
• Subjects with gastrointestinal disease that may significantly alter the absorption of CC-92480.
• Subject has impaired cardiac function or clinically significant cardiac disease, including any of the following:
• LVEF \< 45% as determined by ECHO or MUGA scan at Screening.
• Complete left bundle branch, bifascicular block or other clinically significant abnormal electrocardiographic (ECG) finding at Screening.

Sponsors & Collaborators

• Celgene: lead

Study Sites (54)

Local Institution - 103

Duarte, California, 91010-300, United States

Location

Local Institution - 102

Atlanta, Georgia, 30322, United States

Location

Local Institution - 105

Boston, Massachusetts, 02115, United States

Location

Local Institution - 111

Buffalo, New York, 14263, United States

Location

Local Institution - 104

New York, New York, 10065, United States

Location

Local Institution - 108

Spartanburg, South Carolina, 29303, United States

Location

Local Institution - 101

Nashville, Tennessee, 37203, United States

Location

Local Institution - 106

Houston, Texas, 77030, United States

Location

Local Institution - 112

Charlottesville, Virginia, 22908, United States

Location

Local Institution - 109

Seattle, Washington, 98104, United States

Location

Local Institution - 804

Camperdown, New South Wales, 2050, Australia

Location

Local Institution - 802

Adelaide, South Australia, 5000, Australia

Location

Local Institution - 805

Clayton, Victoria, 3168, Australia

Location

Local Institution - 803

Melbourne, Victoria, 3004, Australia

Location

Local Institution - 806

Fitzroy, 3065, Australia

Location

Local Institution - 904

Antwerp, 2060, Belgium

Location

Local Institution - 905

Ghent, 9000, Belgium

Location

Local Institution - 901

Leuven, 3000, Belgium

Location

Local Institution - 902

Yvoir, 5530, Belgium

Location

Local Institution - 201

Calgary, Alberta, T2N 4N2, Canada

Location

Local Institution - 204

London, Ontario, N6C 6B5, Canada

Location

Local Institution - 205

Ottawa, Ontario, K1H 8L6, Canada

Location

Local Institution - 202

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 206

Montreal, Quebec, H4A 3J1, Canada

Location

Local Institution - 203

Québec, Quebec, G1J 1Z4, Canada

Location

Local Institution - 503

Aarhus N, DK-8200, Denmark

Location

Local Institution - 501

Copenhagen, 2100, Denmark

Location

Local Institution - 502

Odense, 5000, Denmark

Location

Local Institution - 601

Helsinki, 00029, Finland

Location

Local Institution - 001

Athens, 11528, Greece

Location

Local Institution - 705

Chuo-ku,chiba, 260-8677, Japan

Location

Local Institution - 703

Fukuoka, 810-8563, Japan

Location

Local Institution - 704

Kashiwa, 277-8577, Japan

Location

Local Institution - 702

Kobe, 650-0047, Japan

Location

Local Institution - 706

Kyoto, 602-8566, Japan

Location

Local Institution - 701

Okayama, 701-1192, Japan

Location

Local Institution - 152

Seoul, 120-752, South Korea

Location

Local Institution - 150

Seoul, 135-710, South Korea

Location

Local Institution - 151

Seoul, 3080, South Korea

Location

Local Institution - 403

Badalona (Barcelona), 08916, Spain

Location

Local Institution - 407

Barcelona, 08025, Spain

Location

Local Institution - 406

Cáceres, 10003, Spain

Location

Local Institution - 404

Madrid, 28041, Spain

Location

Local Institution - 401

Pamplona, 31008, Spain

Location

Local Institution - 409

Pozuelo de Alarcón, 28223, Spain

Location

Local Institution - 402

Salamanca, 37007, Spain

Location

Local Institution - 408

Santander, 39008, Spain

Location

Local Institution - 405

Valencia, 46026, Spain

Location

Local Institution - 304

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Local Institution - 306

Cardiff, CF14 4XW, United Kingdom

Location

Local Institution - 303

London, NW1 2PG, United Kingdom

Location

Local Institution - 305

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Local Institution - 302

Oxford, OX3 7LE, United Kingdom

Location

Local Institution - 301

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Richardson PG, Trudel S, Popat R, Mateos MV, Vangsted AJ, Ramasamy K, Martinez-Lopez J, Quach H, Orlowski RZ, Arnao M, Lonial S, Karanes C, Pawlyn C, Kim K, Oriol A, Berdeja JG, Rodriguez Otero P, Casas-Aviles I, Spirli A, Poon J, Li S, Gong J, Wong L, Lamba M, Pierce DW, Amatangelo M, Peluso T, Maciag P, Katz J, Pourdehnad M, Bahlis NJ; CC-92480-MM-001 Study Investigators. Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2023 Sep 14;389(11):1009-1022. doi: 10.1056/NEJMoa2303194. Epub 2023 Aug 30.

  PMID: 37646702 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2017
• First Posted: December 15, 2017
• Study Start: February 6, 2018
• Primary Completion: August 20, 2025
• Study Completion: October 23, 2025
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

ES (9); KR (3); GR (1); JP (6); GB (6); FI (1); US (10); CA (6); DK (3); BE (4); AU (5)