Dose-Escalation Study of ABBV-838, an Antibody Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma

NCT ID: NCT02462525

Last Updated: 2018-09-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-06
• Study Completion Date: 2017-12-06

Brief Summary

This is a Phase 1/1b, open-label, dose-escalation study designed to evaluate the safety, pharmacokinetics, and to determine the recommended Phase 2 dose of ABBV-838 in subjects with relapsed and refractory multiple myeloma.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ABBV-838 dose escalation

Varying doses of ABBV-838

Group Type: EXPERIMENTAL

ABBV-838

Intervention Type: DRUG

Varying doses of ABBV-838

ABBV-838 plus pomalidomide/dexamethasone

ABBV-838 to be evaluated with pomalidomide/dexamethasone.

Group Type: EXPERIMENTAL

ABBV-838

Intervention Type: DRUG

Varying doses of ABBV-838

Pomalidomide

Intervention Type: DRUG

Administered orally per the label.

Dexamethasone

Intervention Type: DRUG

Administered orally per the label.

Interventions

ABBV-838

Varying doses of ABBV-838

Intervention Type: DRUG

Pomalidomide

Administered orally per the label.

Intervention Type: DRUG

Dexamethasone

Administered orally per the label.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Eastern Cooperative Oncology Group Performance Status of 0 to 2
• Not eligible for stem cell/bone marrow transplant or have refused stem cell/bone marrow transplant or have relapsed after autologous or allogeneic stem cell/bone marrow transplant
• Eligible for and agree to BM aspirate prior to treatment start
• Measurable disease M component in serum (≥ 0.5 g/dL) and/or urine (≥ 0.2 g excreted in a 24 hour collection sample)
• Must have received at least 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or those who are double refractory to a PI and an immunomodulatory agent and have demonstrated disease progression (DP) on or within 60 days of completion of the last therapy; participants previously treated with an alkylating agent, in addition to an IMiD or proteasome inhibitor, are allowed to enroll in the trial
• Participants must have adequate liver, kidney, and bone morrow function
• Participants with a history of chronic heart failure must have cardiac ECHO indicating left ventricular ejection fraction (LVEF) ≥ 45% within 21 days prior to first dose of study drug
• Participants in the combination therapy arms must be eligible to receive pomalidomide/dexamethasone, bortezomib/dexamethasone or lenalidomide/dexamethasone or other approved agents per current prescribing information for MM.
• Participants who will receive combination therapy with Pomalidomide/Dexamethasone must have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy

Exclusion Criteria

• Received anti-cancer therapy including chemotherapy, immunotherapy, radiation, biologic, any investigational therapy or herbal therapy within a period of 21 days prior to the first dose of ABBV-838, and have unresolved toxicities ≥ grade 2
• Concurrent metastatic solid tumors
• Non-Measurable M Protein (serum or urine) and measurable sFLC (< 100 mg/mL)
• Major surgery within 21 days prior to the first dose of ABBV-838
• Clinically significant uncontrolled condition(s) including but not limited to the following:

Grade ≥ 3 peripheral neuropathy or grade 2 peripheral neuropathy with pain Uncontrolled hypercalcemia Active uncontrolled infection Symptomatic congestive heart failure Unstable angina pectoris or cardiac arrhythmia Psychiatric illness/social situation that would limit compliance with the study

• Major immunologic reaction to any IgG containing agent or auristatin based agent
• Participants who are taking strong CYP3A4 inhibitors
• Positive for HIV (Human Immunodeficiency Virus) or with active hepatitis B and/or C
• Corneal pathology that would limit evaluation of loss in visual acuity associated with corneal deposits.
• Prior exposure to pomalidomide for subjects enrolling in the pomalidomide/dexamethasone combination arm.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

The University of Chicago Medical Center /ID# 139403

Chicago, Illinois, United States

University of Michigan Medical Center /ID# 139402

Ann Arbor, Michigan, United States

Washington University School of Medicine /ID# 135708

St Louis, Missouri, United States

Mount Sinai Medical Center /ID# 133569

New York, New York, United States

The Sarah Cannon Research Institute /ID# 135814

Nashville, Tennessee, United States

CHRU de Lille, Hopital Claude Huriez /ID# 133634

Lille, , France

CHU de Nantes, Hotel Dieu - HME /ID# 133633

Nantes, , France

CHU de la miletrie, Centre d'investigation clinique /ID# 147542

Poitiers, , France

Universitaetsklinikum Koeln /ID# 141535

Cologne, , Germany

Universitaetklinikum Dresden /ID# 141860

Dresden, , Germany

Universitaetsklinikum Heidelberg /ID# 140046

Heidelberg, , Germany

Universitaetsklinikum Schleswig-Holstein /ID# 141534

Kiel, , Germany

Universitaetsklinikum Tuebingen /ID# 141074

Tübingen, , Germany

Universitaetsklinikum Wuerzburg /ID# 141533

Würzburg, , Germany

Hospital Clinic de Barcelona /ID# 141643

Barcelona, , Spain

Hospital Universitario de la Princesa /ID# 140881

Madrid, , Spain

Hospital Universitario 12 de Octubre /ID# 140878

Madrid, , Spain

Clinica Universitaria de Navarra /ID# 141411

Pamplona-Navarra, , Spain

Hospital Clinico Universitario Salamanca /ID# 140880

Salamanca, , Spain

Countries

United States; France; Germany; Spain

References

Vij R, Nath R, Afar DEH, Mateos MV, Berdeja JG, Raab MS, Guenther A, Martinez-Lopez J, Jakubowiak AJ, Leleu X, Weisel K, Wong S, Gulbranson S, Sheridan JP, Reddy A, Paiva B, Singhal A, San-Miguel JF, Moreau P. First-in-Human Phase I Study of ABBV-838, an Antibody-Drug Conjugate Targeting SLAMF7/CS1 in Patients with Relapsed and Refractory Multiple Myeloma. Clin Cancer Res. 2020 May 15;26(10):2308-2317. doi: 10.1158/1078-0432.CCR-19-1431. Epub 2020 Jan 22.

Reference Type: DERIVED

PMID: 31969330 (View on PubMed)

Other Identifiers

2014-002609-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M14-467

Identifier Type: -

Identifier Source: org_study_id