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

AbbVie

Status and phase: Terminated; Phase 1

Conditions: Multiple Myeloma

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02462525

2014-002609-39 (EudraCT Number)

M14-467

Details and patient eligibility

About

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.

Enrollment: 74 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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74 participants in 2 patient groups

ABBV-838 dose escalation

Experimental group

Description:

Varying doses of ABBV-838

Treatment:

Drug: ABBV-838

ABBV-838 plus pomalidomide/dexamethasone

Experimental group

Description:

ABBV-838 to be evaluated with pomalidomide/dexamethasone.

Treatment:

Drug: ABBV-838

Drug: Pomalidomide

Drug: Dexamethasone