dose-escalation study of abbv-838, an antibody drug conjugate, in subjects with relapsed and refractory multiple myeloma

Conditions: Multiple Myeloma

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.

Keywords: relapsed multiple myeloma antibody drug conjugate refractory multiple myeloma