Clinical trial NCT02462525: Dose-Escalation Study of ABBV-838, an Antibody Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma
Official title: A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABBV-838, an Antibody Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: relapsed multiple myeloma
antibody drug conjugate
refractory multiple myeloma
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2015-06-04
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Maximum plasma concentration (Cmax) of ABBV-838
timeFrame: 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
measure: Maximum tolerated dose of ABBV-838
timeFrame: Up to 2 years from first dose of study
Secondary outcomes:
measure: Preliminary activity of ABBV-838 monotherapy
timeFrame: 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
Other outcomes:
Locations:
city: Chicago
country: United States
facility: The University of Chicago Medical Center /ID# 139403
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center /ID# 139402
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine /ID# 135708
state: Missouri
city: New York
country: United States
facility: Mount Sinai Medical Center /ID# 133569
state: New York
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute /ID# 135814
state: Tennessee
city: Lille Cedex
country: France
facility: CHRU de Lille, Hopital Claude Huriez /ID# 133634
city: Nantes Cedex 1
country: France
facility: CHU de Nantes, Hotel Dieu - HME /ID# 133633
city: Poitiers
country: France
facility: CHU de la miletrie, Centre d'investigation clinique /ID# 147542
city: Cologne
country: Germany
facility: Universitaetsklinikum Koeln /ID# 141535
city: Dresden
country: Germany
facility: Universitaetklinikum Dresden /ID# 141860
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg /ID# 140046
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein /ID# 141534
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen /ID# 141074
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg /ID# 141533
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona /ID# 141643
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa /ID# 140881
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre /ID# 140878
city: Pamplona-Navarra
country: Spain
facility: Clinica Universitaria de Navarra /ID# 141411
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario Salamanca /ID# 140880
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.