A Study to Assess Adverse Events and Change in Disease Activity of Intravenously (IV) Infused ABBV-383 in Combination With Anti-Cancer Regimens for the Treatment of Adult Participants With Relapsed/Refractory Multiple Myeloma

A Dose Escalation and Expansion Study of ABBV-383 in Combination With Anti-Cancer Regimens for the Treatment of Patients With Relapsed/Refractory 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 toxicity of ABBV-383 when co-administered with pomalidomide-dexamethasone (Pd), lenalidomide-dexamethasone (Rd), daratumumab-dexamethasone (Dd), or nirogacestat (Niro) in adult participants with relapsed/refractory (R/R) multiple myeloma (MM). Adverse events and change in disease activity will be assessed.

ABBV-383 is an investigational drug being developed for the treatment of R/R MM. Study doctors put the participants in groups called treatment arms. ABBV-383 co-administered with Pd, Rd, Dd, or Niro will be explored. Each treatment arm receives a different treatment combination depending on stage of the study and eligibility. This study will include a dose escalation phase to determine the best dose of ABBV-383, followed by a dose expansion phase to confirm the dose. Approximately 270 adult participants with R/R MM will be enrolled in the study in approximately 45 sites worldwide.

Participants will receive intravenous (IV) ABBV-383 co-administered with oral/IV Pd, oral/IV Rd, oral/IV/subcutaneous (SC) Dd, or oral/IV Niro in 28-day cycles.

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 (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Drug: ABBV-383; Drug: Dexamethasone; Drug: Pomalidomide; Drug: Lenalidomide; Drug: Daratumumab; Drug: Nirogacestat

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: 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
    • Kogarah, New South Wales, Australia, 2217
      • Recruiting
      • St George Hospital /ID# 243740
    • Waratah, New South Wales, Australia, 2298
      • Recruiting
      • Calvary Mater Newcastle /ID# 243730
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre /ID# 244403
    • Fitzroy Melbourne, Victoria, Australia, 3065
      • Recruiting
      • St Vincent's Hospital Melbourne /ID# 256879
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Ctr /ID# 256880
    • Richmond, Victoria, Australia, 3121
      • Recruiting
      • Epworth Healthcare /ID# 243734
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Recruiting
      • Fiona Stanley Hospital /ID# 244753
• Germany
  • Essen, Germany, 45147
    • Recruiting
    • Universitaetsklinikum Essen /ID# 242819
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitaetsklinikum Hamburg-Eppendorf /ID# 243141
  • Regensburg, Germany, 93042
    • Recruiting
    • Universitaetsklinikum Regensburg /ID# 242837
  • Wuerzburg, Germany, 97080
    • Recruiting
    • Universitaetsklinikum Wuerzburg /ID# 242826
  • Baden-Wuerttemberg
    • Tubingen, Baden-Wuerttemberg, Germany, 72076
      • Recruiting
      • Universitaetsklinikum Tuebingen /ID# 242815
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 242581
  • Meldola, Italy, 47014
    • Recruiting
    • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRCCS /ID# 242584
  • Milan, Italy, 20122
    • Recruiting
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 244057
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 242582
  • Milano
    • Milan, Milano, Italy, 20132
      • Recruiting
      • Ospedale San Raffaele IRCCS /ID# 242583
• Japan
  • Aichi
    • Nagoya shi, Aichi, Japan, 467-8602
      • Recruiting
      • Nagoya City University Hospital /ID# 249094
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East /ID# 245889
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060-8648
      • Recruiting
      • Hokkaido University Hospital /ID# 245966
  • Ishikawa
    • Kanazawa-shi, Ishikawa, Japan, 920-8641
      • Recruiting
      • Kanazawa University Hospital /ID# 246812
  • Okayama
    • Okayama-shi, Okayama, Japan, 701-1192
      • Recruiting
      • Okayama Medical Center /ID# 245882
  • Yamagata
    • Yamagata-shi, Yamagata, Japan, 990-9585
      • Recruiting
      • Yamagata University Hospital /ID# 245888
• Poland
  • Dolnoslaskie
    • Opole, Dolnoslaskie, Poland, 45-372
      • Recruiting
      • Szpital Wojewodzki w Opolu sp. z o.o. /ID# 243954
    • Wroclaw, Dolnoslaskie, Poland, 50-556
      • Recruiting
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocawiu /ID# 243246
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-081
      • Recruiting
      • Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie /ID# 243500
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-214
      • Recruiting
      • Uniwersyteckie Centrum Kliniczne /ID# 243249
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitario Vall d'Hebron /ID# 242976
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic de Barcelona /ID# 242978
  • Madrid, Spain, 28027
    • Recruiting
    • CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 244145
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre /ID# 242975
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio /ID# 242974
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • Hospital Duran i Reynals /ID# 242979
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 242977
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas for Medical Sciences /ID# 243096
  • Florida
    • Miami, Florida, United States, 33136-1002
      • Recruiting
      • Sylvester Comprehensive Cancer Center /ID# 243673
    • Tampa, Florida, United States, 33612-9416
      • Recruiting
      • Moffitt Cancer Center /ID# 243437
  • Maryland
    • Baltimore, Maryland, United States, 21201-1544
      • Recruiting
      • University of Maryland School of Medicine /ID# 243679
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute /ID# 249529
      • Contact: Site Coordinator; Phone Number: (617) 632-3000
    • Worcester, Massachusetts, United States, 01655
      • Recruiting
      • University of Massachusetts - Worcester /ID# 243977
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 243438
  • New Jersey
    • Paramus, New Jersey, United States, 07652
      • Recruiting
      • The Valley Hospital /ID# 243829
  • New York
    • New York, New York, United States, 10029-6030
      • Recruiting
      • Rutenberg Cancer Center /ID# 244647
    • New York, New York, United States, 10065-6007
      • Recruiting
      • Memorial Sloan Kettering Cancer Center /ID# 244656
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute /ID# 242851
  • Texas
    • Dallas, Texas, United States, 75390-7208
      • Recruiting
      • University of Texas Southwestern Medical Center /ID# 243273
      • Contact: Site Coordinator; Phone Number: 214-648-3111
  • Utah
    • Salt Lake City, Utah, United States, 84112-5500
      • Recruiting
      • Huntsman Cancer Institute /ID# 242872
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • University of Washington /ID# 243172
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3522
      • Recruiting
      • Froedtert Memorial Lutheran Hospital /ID# 242654

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance of <= 2.
• Must have confirmed diagnosis of Relapsed/Refractory (R/R) Multiple Myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen based on the investigator's determination of the International Myeloma Working Group (IMWG) criteria.
• Must have measurable disease as outlined in the protocol.
• Must be naïve to treatment with ABBV-383 and must have never received BCMA-targeted therapy. Participants who have received targeted therapy against non-BCMA targets will not be excluded.
• Has received prior MM treatment in Arms A, B, C, and D.

Exclusion Criteria:

• Received a peripheral autologous stem cell transplant (SCT) within 12 weeks, or an allogeneic SCT within 1 year of the first dose of study drug treatment.
• Unresolved adverse event (AE)s >= Grade 2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from prior anticancer therapy.
• Known central nervous system involvement Multiple Myeloma (MM).

• Has any of the following conditions:

  • Nonsecretory MM.
  • Active Plasma cell leukemia i.e., either 20% of peripheral white blood cells or > 2.0 × 10^9L circulating plasma cells by standard differential.
  • Waldenstrom's macroglobulinemia.
  • Light chain amyloidosis.
  • Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome.
  • Major surgery within 4 weeks prior to first dose or planned study participation.
  • Acute infections within 14 days prior to first dose of study drug requiring therapy (antibiotic, antifungal or antiviral).
  • Uncontrolled diabetes or hypertension within 14 days prior to first dose.
  • Peripheral neuropathy >= Grade 3 or >= Grade 2 with pain within 2 weeks prior to first dose.
• Known active infection of evidence of active hepatitis B, evidence of active hepatitis C, human immunodeficiency virus.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (ABBV-383 with Pomalidomide and Dexamethasone); Participants with relapsed or refractory (R/R) multiple myeloma (MM) who meet the criteria outline in the protocol will receive ABBV-383 with Pomalidomide and Dexamethasone.	Drug: ABBV-383; Intravenous (IV) Infusion; Drug: Dexamethasone; Oral; Tablet or IV Infusion; Drug: Pomalidomide; Oral; Capsule
Experimental: Arm B (ABBV-383 with Lenalidomide and Dexamethasone); Participants with R/R MM who meet the criteria outline in the protocol will receive ABBV-383 with Lenalidomide and Dexamethasone.	Drug: ABBV-383; Intravenous (IV) Infusion; Drug: Dexamethasone; Oral; Tablet or IV Infusion; Drug: Lenalidomide; Oral; Capsule
Experimental: Arm C (ABBV-383 with Daratumumab and Dexamethasone); Participants with R/R MM who meet the criteria outline in the protocol will receive ABBV-383 with Daratumumab and Dexamethasone.	Drug: ABBV-383; Intravenous (IV) Infusion; Drug: Dexamethasone; Oral; Tablet or IV Infusion; Drug: Daratumumab; Subcutaneous Injection (SC)
Experimental: Arm D (ABBV-383 with Nirogacestat); Participants with R/R MM who meet the criteria outline in the protocol will receive ABBV-383 with Nirogacestat.	Drug: ABBV-383; Intravenous (IV) Infusion; Drug: Nirogacestat; Oral; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Dose Limiting Toxicities (DLT) of ABBV-383	DLT events as described in the protocol will be assessed.	Up to approximately 28 Days
Number of Participants with Adverse Events (AEs)	An AE 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. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.	Up to Approximately 3 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR is defined as partial response(PR) + very good partial response (VGPR) + complete remission (CR) + stringent complete response (sCR); proportion of participants who achieved a PR or better.	Up to Approximately 3 Years
Progression-Free Survival (PFS)	PFS is defined as the number of days from the date of first dose to the date of earliest disease progression or death.	Up to Approximately 3 Years
Duration of Response (DOR)	DOR will be defined as the number of days from the date of first response (sCR, CR, VGPR, or PR) to the earliest recurrence, progressive disease, or death, whatever occurs first.	Up to Approximately 3 Years
Time-to-Progression (TTP)	TTP is defined as the number of days from the date of first dose to the date of earliest disease progression.	Up to Approximately 3 Years
Percentage of Participants with Minimal Residual Disease Negativity (MRD)	MRD is defined as the percentage of participants with assessment of the minimal residual disease.	Up to Approximately 3 Years

Collaborators and Investigators

• Sponsor: TeneoOne Inc.
• Investigators: Study Director: TeneoOne Inc, TeneoOne Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Estimated): November 29, 2028
• Study Completion (Estimated): July 21, 2031

Study Registration Dates

• First Submitted: February 18, 2022
• First Submitted That Met QC Criteria: February 18, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pomalidomide; Cancer; Daratumumab; Lenalidomide; Dexamethasone; Relapsed/Refractory Multiple Myeloma; Nirogacestat; ABBV-383
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Gamma Secretase Inhibitors and Modulators; Dexamethasone; Pomalidomide; Lenalidomide; Daratumumab; Nirogacestat
• Other Study ID Numbers: M22-947; 2021-005587-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: Yes