Multiple Myeloma
Conditions
Keywords
relapsed multiple myeloma, antibody drug conjugate, refractory multiple myeloma
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.
Interventions
DRUGABBV-838
Varying doses of ABBV-838
DRUGPomalidomide
Administered orally per the label.
DRUGDexamethasone
Administered orally per the label.
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration (Cmax) of ABBV-838 | 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 | 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. |
| Maximum tolerated dose of ABBV-838 | Up to 2 years from first dose of study | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Response evaluation will be based on International Myeloma Working Group (IMWG) Response Criteria. |
Countries
France, Germany, Spain, United States
Outcome results
None listed