A Study to Assess Adverse Events and Change in Disease Activity of Oral Surzetoclax Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM)

A Phase 1/2, Open-Label, Platform Study to Evaluate Safety and Efficacy of the BCL-2 Inhibitor Surzetoclax (ABBV-453) Given as Monotherapy or in Combination With Antimyeloma Regimens in Subjects With Multiple Myeloma

Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the safety and change in disease activity of surzetoclax in adult participants with relapsed/refractory (R/R) MM. Adverse events and change in disease activity will be assessed.

Surzetoclax is an investigational drug being developed for the treatment of R/R MM. In Substudy 1 there will be a dose escalation phase where participants will receive various doses of surzetoclax in combination with daratumumab + dexamethasone, to determine the best dose of surzetoclax. This will be followed by a dose expansion and selection phase where participants will receive 1 of 2 doses of surzetoclax in combination with daratumumab + dexamethasone, or daratumumab + dexamethasone + pomalidomide (only during the expansion phase). In Substudy 2, there will be a dose escalation phase where participants will receive various doses of surzetoclax alone. Approximately 130 adult participants with R/R MM will be enrolled in the study in approximately 40 sites worldwide.

In Substudy 1 escalation phase, participants will receive oral surzetoclax tablets in combination with subcutaneous (SC) daratumumab injections + oral dexamethasone tablets and in the expansion phase, will receive oral surzetoclax tablets in combination with SC daratumumab injections + oral dexamethasone tablets or daratumumab injections + oral pomalidomide + oral dexamethasone tablets. In Substudy 2, Japanese participants will receive oral surzetoclax tablets. The total study duration is approximately 4.5 years.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution. The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Dexamethasone; Drug: Pomalidomide; Drug: ABBV-453; Drug: Daratumumab

• Study Type: Interventional
• Enrollment (Estimated): 199
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Recruiting
      • Liverpool Hospital /ID# 272002
    • Waratah, New South Wales, Australia, 2298
      • Recruiting
      • Calvary Mater Newcastle /ID# 272498
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St Vincent's Hospital - Melbourne /ID# 271997
    • Richmond, Victoria, Australia, 3121
      • Recruiting
      • Epworth Hospital - Richmond /ID# 272497
• Belgium
  • Liège, Belgium, 4000
    • Recruiting
    • CHU de Liege /ID# 271430
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • Recruiting
      • UZ Gent /ID# 271432
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • Universitair Ziekenhuis Leuven /ID# 272382
• France
  • Herault
    • Montpellier, Herault, France, 34295
      • Recruiting
      • CHU de Montpellier - Hopital Saint Eloi /ID# 275570
  • New Aquitaine
    • Poitiers, New Aquitaine, France, 86021
      • Recruiting
      • Centre Hospitalier Universitaire de Poitiers /ID# 275563
  • Occitanie
    • Toulouse, Occitanie, France, 31059
      • Recruiting
      • IUCT Oncopole /ID# 275568
  • Pays de la Loire Region
    • Nantes, Pays de la Loire Region, France, 44000
      • Recruiting
      • Centre Hospitalier Universitaire de Nantes, Hotel Dieu -HME /ID# 275562
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75015
      • Recruiting
      • Hopital Universitaire Necker Enfants Malades /ID# 275571
• Germany
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitaetsklinikum Hamburg-Eppendorf /ID# 275803
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Recruiting
      • Universitaetsklinikum Heidelberg /ID# 275598
  • Bavaria
    • Munich, Bavaria, Germany, 81337
      • Recruiting
      • Klinikum der Universitaet Muenchen Grosshadern /ID# 276658
    • Würzburg, Bavaria, Germany, 97080
      • Recruiting
      • Universitaetsklinikum Wuerzburg /ID# 276657
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus- Haifa /ID# 271256
  • Jerusalem, Israel, 91120
    • Recruiting
    • Hadassah Medical Center-Hebrew University /ID# 271253
  • Central District
    • Petah Tikva, Central District, Israel, 4941492
      • Recruiting
      • Rabin Medical Center. /ID# 272073
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 5265601
      • Recruiting
      • The Chaim Sheba Medical Center /ID# 271251
    • Tel Aviv, Tel Aviv, Israel, 6423906
      • Recruiting
      • Tel Aviv Sourasky Medical Center /ID# 271252
• Italy
  • Milan, Italy, 20122
    • Recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico /ID# 276306
• Japan
  • Tokyo, Japan, 105-8461
    • Recruiting
    • The Jikei University Hospital /ID# 272091
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 467-8602
      • Recruiting
      • Nagoya City University Hospital /ID# 271427
  • Kyoto
    • Kyoto, Kyoto, Japan, 602-8566
      • Recruiting
      • University Hospital Kyoto Prefectural University of Medicine /ID# 271911
  • Osaka
    • Suita-shi, Osaka, Japan, 565-0871
      • Recruiting
      • The University of Osaka Hospital /ID# 271636
  • Tokyo
    • Shibuya-ku, Tokyo, Japan, 150-8935
      • Recruiting
      • Japanese Red Cross Medical Center /ID# 272018
• Poland
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-090
      • Recruiting
      • Uniwersytecki Szpital Kliniczny Nr 4 w Lublinie /ID# 276352
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Recruiting
      • Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Bada /ID# 276263
• Portugal
  • Braga, Portugal, 4710-243
    • Recruiting
    • Unidade Local de Saude de Braga, EPE /ID# 275853
  • Porto, Portugal, 4200-072
    • Recruiting
    • Instituto Portugues de Oncologia do Porto Francisco Gentil /ID# 275851
  • Lisbon District
    • Lisbon, Lisbon District, Portugal, 1099-023
      • Recruiting
      • Instituto Portugues de Oncologia de Lisboa Francisco Gentil /ID# 275873
• Sweden
  • Stockholm County
    • Solna, Stockholm County, Sweden, 171 64
      • Recruiting
      • Karolinska University Hospital Solna /ID# 271674
  • Västra Götaland County
    • Borås, Västra Götaland County, Sweden, 501 82
      • Recruiting
      • Sodra Alvsborgs sjukhus /ID# 271822
    • Gothenburg, Västra Götaland County, Sweden, 41346
      • Recruiting
      • Sahlgrenska Universitetssjukhuset /ID# 272448
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust - Christie Hospital /ID# 276276
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California /ID# 272414
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale University School of Medicine /ID# 272447
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute /ID# 271846
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Health System - Ann Arbor /ID# 271536
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center - New York - York Avenue /ID# 271214
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • University of North Carolina at Chapel Hill /ID# 272454
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Atrium Health Levine Cancer Institute /ID# 271510
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Wake Forest Baptist Health /ID# 271294
  • Texas
    • Dallas, Texas, United States, 75235
      • Recruiting
      • University of Texas - Southwestern Medical Center /ID# 271914
  • Washington
    • Tacoma, Washington, United States, 98405
      • Recruiting
      • Northwest Medical Specialties Tacoma /ID# 272506

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Documented diagnosis of multiple myeloma (MM) based on standard international myeloma working group (IMWG) diagnostic criteria.

• All participants must have measurable disease per central laboratory with at least 1 of the following assessed within 28 days prior to enrollment:

  • Serum M-protein >= 0.5 g/dL (>= 5g/L); OR
  • Urine M-protein >= 200 mg/24 hours; OR
  • For participants without measurable serum and urine M-protein: Serum free light chain (sFLC) ≥ 10 mg/dL (100 mg/L), provided sFLC ratio is abnormal.
• B-cell lymphoma (BCL)-2 inhibitor treatment naïve.
• t(11;14) positive status and/or BCL2 high status.

• Substudy 1 Dose Escalation Cohorts and Substudy 2:

  -- Must be triple class exposed (PI, IMiD and anti-CD38) and have received 3 to 5 lines of prior antimyeloma therapy, and who have no other appropriate treatment options as deemed by the investigator.

• Substudy 1 Dose Expansion Cohorts:

  • Must be double class exposed (PI, IMiD) and have received 1 to 3 lines of prior antimyeloma therapy.

Exclusion Criteria:

• Major surgery within 4 weeks of study treatment or planned during study participation.
• Active infections: no recent infection requiring systemic treatment that was completed <= 7 days before first dose of study treatment and/or uncontrolled systemic infection.
• Recent infection requiring systemic treatment that was completed <= 7 days before first dose of study treatment and/or uncontrolled active systemic infection.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Substudy 1: Dose Escalation ABBV-453 Combination; Participants will receive various doses of ABBV-453 in combination with daratumumab + dexamethasone, to determine the best dose of ABBV-453, as part of the total 4.5 year study duration.	Drug: Dexamethasone; Oral Tablet; Drug: ABBV-453; Oral Tablet; Drug: Daratumumab; Subcutaneous (SC) Injection
Experimental: Substudy 1: Dose Expansion and Selection ABBV-453 Combination; Participants will receive 1 of 2 doses of ABBV-453 in combination with daratumumab + dexamethasone, as part of the total 4.5 year study duration.	Drug: Dexamethasone; Oral Tablet; Drug: ABBV-453; Oral Tablet; Drug: Daratumumab; Subcutaneous (SC) Injection
Active Comparator: Substudy 1: Dose Expansion and Selection Control; Participants will receive daratumumab, dexamethasone, and pomalidomide, as part of the total 4.5 year study duration.	Drug: Dexamethasone; Oral Tablet; Drug: Pomalidomide; Oral Capsule; Drug: Daratumumab; Subcutaneous (SC) Injection
Experimental: Substudy 2: Dose Escalation ABBV-453 Monotherapy; Japanese participants will receive various doses of ABBV-453 as a monotherapy, to determine the best dose of ABBV-453, as part of the total 4.5 year study duration.	Drug: ABBV-453; Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicities (DLT)s of ABBV-453	DLT events are defined as specific clinically significant adverse events or abnormal laboratory values assessed as events regardless of attribution to ABBV-453, except those clearly and incontrovertibly associated with underlying disease or extraneous causes.	Up to Approximately 45 Months
Number of Participants with Adverse Events (AE)s	An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.	Up to Approximately 4.5 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR is defined as the percentage of participants with a confirmed partial response (PR), very good partial response, complete response (CR) or stringent complete response (sCR) per Investigator review according to International Myeloma Working Group (IMWG) 2016 criteria.	Up to Approximately 4.5 Years
Progression-Free Survival (PFS)	PFS is defined as time from first study treatment to the earliest documented disease progression according to IMWG 2016 criteria, as determined by the investigator, or death due to any cause, whichever occurs earlier.	Up to Approximately 4.5 Years
Duration of Response (DOR)	DOR is defined as the time from the date of achieving the first confirmed sCR/CR/VGPR/PR to the date of recurrence disease progression according to IMWG 2016 criteria, as determined by the investigator, or death of any cause, whichever occurs earlier.	Up to Approximately 4.5 Years
Time-to-Progression (TTP)	TTP will be defined as the number of days from the date of first dose to the date of earliest disease progression.	Up to Approximately 4.5 Years
Time to Next Treatment	Time to next treatment will be defined as the number of days from the date of first dose to the date of next treatment.	Up to Approximately 4.5 Years
Minimal Residual Disease (MRD) Negativity	MRD negativity is defined as having less than 1 myeloma cell that may remain in the bone marrow aspirate per 10^5 nucleated cells and rate of MRD negativity will be determined.	Up to Approximately 4.5 Years
Overall Survival (OS)	OS is defined as time from first study treatment to death due to any cause.	Up to Approximately 4.5 Years

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: April 17, 2025
• First Submitted That Met QC Criteria: April 24, 2025
• First Posted (Actual): May 1, 2025

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pomalidomide; Cancer; Multiple Myeloma; Daratumumab; Dexamethasone; ABBV-453; Surzetoclax
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Neoplasms; Multiple Myeloma; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Dexamethasone; pomalidomide; daratumumab
• Other Study ID Numbers: M25-275; 2024-517140-65 (Other Identifier: EU CT); 2024-517140-65-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing, visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No