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

Study Overview
=================
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.

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

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: ABBV-838
* Drug: Pomalidomide
* Drug: Dexamethasone


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABBV-838 dose escalation<br>Varying doses of ABBV-838 | Drug: ABBV-838<br>* Varying doses of ABBV-838<br>|
| Experimental: ABBV-838 plus pomalidomide/dexamethasone<br>ABBV-838 to be evaluated with pomalidomide/dexamethasone. | Drug: ABBV-838<br>* Varying doses of ABBV-838<br>Drug: Pomalidomide<br>* Administered orally per the label.<br>Drug: Dexamethasone<br>* Administered orally per the label.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary activity of ABBV-838 monotherapy | Response evaluation will be based on International Myeloma Working Group (IMWG) Response Criteria. | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
relapsed multiple myeloma, antibody drug conjugate, refractory multiple myeloma