Study of AO-176 as Monotherapy and in Combination With Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma

Arch Oncology10 enrolled

Overview

Open-label, dose escalation study to evaluate the safety, tolerability, pharmacokinetics (PK)/pharmacodynamics and initial efficacy of AO-176 as monotherapy and in combination with dexamethasone and bortezomib in adults with relapsed/refractory multiple myeloma (MM).

An open-label, multicenter, dose escalation study to evaluate the safety, tolerability and PK/pharmacodynamics of AO-176 in adults with relapsed/refractory multiple myeloma whose disease has progressed following at least 3 prior systemic lines of treatment and must have progressed on the final line of therapy received before being considered for this study. The study will be conducted in 2 phases; Phase 1 is an ascending-dose study of AO-176 monotherapy utilizing the classic 3+3 design, with enrollment of 3 patients per cohort and expansion of the cohort in the event of a dose-limiting toxicity (DLT). Following the dose escalation portion and determination of the monotherapy recommended phase 2 dose (RP2D), an ascending dose escalation study of AO-176 and dexamethasone combined with bortezomib will be evaluated utilizing the same 3+3 dose escalation design. Phase 2 will evaluate the clinical activity of AO-176 plus dexamethasone and bortezomib at the RP2D as determined in Phase 1 Part 2.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

AO-176DRUG

Humanized monoclonal antibody (mAb) targeting CD47

AO-176 + DexDRUG

Humanized mAb targeting CD47 plus dexamethasone

AO-176 + Dex + BortDRUG

Humanized mAb targeting CD47 plus dexamethasone plus bortezomib

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Confirmed diagnosis of symptomatic MM per IMWG criteria 2. Measurable disease 3. Relapsed or refractory to at least 3 prior systemic lines of therapy for MM 4. Eastern Cooperative Oncology Group (ECOG) status 0-2 5. Resolution of prior therapy-related adverse events 6. Minimum of 2 weeks since last dose of cancer therapy or radiotherapy Key Exclusion Criteria: 1. Previous Grade 3-4 infusion or hypersensitivity reaction 2. Severe asthma or chronic obstructive pulmonary disease exacerbations requiring hospital admission or steroids 3. Prior treatment with a checkpoint inhibitor (anti-PD-1, PD-L1 or CTLA-4) within 4 weeks. 4. Prior treatment with a therapeutic agent that targets the CD47 axis.

Locations (6)

Mayo Clinic

Phoenix, Arizona, United States

Mayo Clinic

Jacksonville, Florida, United States

Emory University

Atlanta, Georgia, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

Phase 1: MTD / RP2D of AO-176 assessed by incidence of dose-limiting toxicities and incidence of treatment-related adverse events (TEAEs) as assessed by CTCAE v5.0

Safety and tolerability of AO-176 when administered as monotherapy and in combination with dexamethasone or with dexamethasone plus bortezomib in adult patients with R/R MM as assessed by incidence of DLTs and TEAEs as assessed by CTCAE v5.0

Time frame: 12 months

Phase 2: Objective response rate (ORR) of AO-176 + DEX + BORT

Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on ORR using International Myeloma Working Group (IMWG) uniform response criteria

Time frame: 12 months

Secondary Outcomes

Phase 1: ORR of single agent AO-176

Evaluate the clinical activity of single agent AO-176 based on ORR using IMWG uniform response criteria

Time frame: 12 months

Phase 1: Duration of response (DOR) of single agent AO-176

Evaluate the clinical activity of single agent AO-176 based on DOR using IMWG uniform response criteria

Time frame: 12 months

Phase 1: Disease control rate (DCR) of single agent AO-176

Evaluate the clinical activity of single agent AO-176 based on DCR using IMWG uniform response criteria

Time frame: 12 months

Phase 1: Progression-free survival (PFS) of single agent AO-176

Evaluate the clinical activity of single agent AO-176 based on PFS using IMWG uniform response criteria

Time frame: 12 months

Phase 1: Overall survival (OS) of single agent AO-176

Data from ClinicalTrials.gov

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