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

NCT02462525 | Terminated Phase 1

• 2 other identifiers: M14-4672014-002609-39
• Study Type: interventional
• Target: 74
• Locations: 4 countries
• Sites: 19

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

Keywords

relapsed multiple myeloma; antibody drug conjugate; refractory multiple myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum plasma concentration (Cmax) of ABBV-838

  The maximum plasma concentration (Cmax: measured in ng/ml) is the highest concentration that a drug achieves in the blood after the first dose, but before administration of a second dose.

  Cycle 1 Day 1 (C1D1) and C3D1 pre- and post-dose; C1D4, C1D8, C1D15, C2D1, C2D15, C3D4, C3D8, C3D15, C4D1, and all subsequent ABBV-838 pre-dose dosing cycles

• Maximum tolerated dose of ABBV-838

  The highest dose level at which less than 2 of 6 subjects or less than 33% of (if cohort is expanded beyond 6) subjects experience a dose limiting toxicity.

  Up to 2 years from first dose of study

Secondary Outcomes (1)

• Preliminary activity of ABBV-838 monotherapy

  At screening, Cycle 1 Day 15 (C1D15), C3D15, C4D1, and for subjects who have been on ABBV-838 for ≥ 6 cycles, radiologic tumor assessments may be performed every 3 cycles per Investigator discretion up to approximately 3 years

Study Arms (2)

ABBV-838 dose escalation

EXPERIMENTAL

Varying doses of ABBV-838

Drug: ABBV-838

ABBV-838 plus pomalidomide/dexamethasone

EXPERIMENTAL

ABBV-838 to be evaluated with pomalidomide/dexamethasone.

Drug: ABBV-838; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

ABBV-838 DRUG

Varying doses of ABBV-838

ABBV-838 dose escalation; ABBV-838 plus pomalidomide/dexamethasone

Pomalidomide DRUG

Administered orally per the label.

ABBV-838 plus pomalidomide/dexamethasone

Dexamethasone DRUG

Administered orally per the label.

ABBV-838 plus pomalidomide/dexamethasone

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (19)

The University of Chicago Medical Center /ID# 139403

Chicago, Illinois, 60637, United States

Location

University of Michigan Medical Center /ID# 139402

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine /ID# 135708

St Louis, Missouri, 63110-1093, United States

Location

Mount Sinai Medical Center /ID# 133569

New York, New York, 10029, United States

Location

The Sarah Cannon Research Institute /ID# 135814

Nashville, Tennessee, 37203, United States

Location

CHRU de Lille, Hopital Claude Huriez /ID# 133634

Lille, 59037, France

Location

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

Nantes, 44093, France

Location

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

Poitiers, 86021, France

Location

Universitaetsklinikum Koeln /ID# 141535

Cologne, 50937, Germany

Location

Universitaetklinikum Dresden /ID# 141860

Dresden, 01307, Germany

Location

Universitaetsklinikum Heidelberg /ID# 140046

Heidelberg, 69210, Germany

Location

Universitaetsklinikum Schleswig-Holstein /ID# 141534

Kiel, 24105, Germany

Location

Universitaetsklinikum Tuebingen /ID# 141074

Tübingen, 72076, Germany

Location

Universitaetsklinikum Wuerzburg /ID# 141533

Würzburg, 97080, Germany

Location

Hospital Clinic de Barcelona /ID# 141643

Barcelona, 08036, Spain

Location

Hospital Universitario de la Princesa /ID# 140881

Madrid, 28006, Spain

Location

Hospital Universitario 12 de Octubre /ID# 140878

Madrid, 28041, Spain

Location

Clinica Universitaria de Navarra /ID# 141411

Pamplona-Navarra, 31008, Spain

Location

Hospital Clinico Universitario Salamanca /ID# 140880

Salamanca, 37007, Spain

Location

Related Publications (1)

• 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.

  PMID: 31969330 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pomalidomide; 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

Intervention Hierarchy (Ancestors)

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

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 26, 2015
• First Posted: June 4, 2015
• Study Start: May 6, 2015
• Primary Completion: December 6, 2017
• Study Completion: December 6, 2017
• Last Updated: September 13, 2018

Record last verified: 2018-09

Locations

ES (5); DE (6); US (5); FR (3)