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

NCT04445701 | Completed Phase 1 FDA Drug

• 1 other identifier: AO-176-102
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 6

Brief Summary

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).

Conditions

Multiple Myeloma

Keywords

AO-176; CD47; Immunotherapy; Monoclonal antibody

Outcome Measures

Primary Outcomes (2)

• 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

  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

  12 months

Secondary Outcomes (9)

• Phase 1: ORR of single agent AO-176

  12 months

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

  12 months

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

  12 months

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

  12 months

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

  12 months

Study Arms (3)

AO-176 Dose Escalation Monotherapy

EXPERIMENTAL

The dose escalation monotherapy cohorts will initially recruit 3 patients to receive AO-176 in a standard 3+3 design; cohorts will be expanded in the event of a DLT.

Drug: AO-176

AO-176 + DEX Expansion Cohort

EXPERIMENTAL

Once the monotherapy RP2D has been established, an expansion cohort of AO-176 + dexamethasone will be enrolled.

Drug: AO-176 + Dex

AO-176 + DEX + BORT Dose Escalation

EXPERIMENTAL

Following evaluation of AO-176 + dexamethasone, dose escalation cohorts of AO-176 + dexamethasone + bortezomib will be enrolled. Each dose escalation cohort will initially recruit 3 patients in a standard 3+3 design; cohorts will be expanded in the event of a DLT. The Phase 2 portion of the study will further evaluate the RP2D of AO-176 + DEX + BORT.

Drug: AO-176 + Dex + Bort

Interventions

AO-176 DRUG

Humanized monoclonal antibody (mAb) targeting CD47

AO-176 Dose Escalation Monotherapy

AO-176 + Dex DRUG

Humanized mAb targeting CD47 plus dexamethasone

AO-176 + DEX Expansion Cohort

AO-176 + Dex + Bort DRUG

Humanized mAb targeting CD47 plus dexamethasone plus bortezomib

AO-176 + DEX + BORT Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of symptomatic MM per IMWG criteria
• Measurable disease
• Relapsed or refractory to at least 3 prior systemic lines of therapy for MM
• Eastern Cooperative Oncology Group (ECOG) status 0-2
• Resolution of prior therapy-related adverse events
• Minimum of 2 weeks since last dose of cancer therapy or radiotherapy

You may not qualify if:

• Previous Grade 3-4 infusion or hypersensitivity reaction
• Severe asthma or chronic obstructive pulmonary disease exacerbations requiring hospital admission or steroids
• Prior treatment with a checkpoint inhibitor (anti-PD-1, PD-L1 or CTLA-4) within 4 weeks.
• Prior treatment with a therapeutic agent that targets the CD47 axis.

Sponsors & Collaborators

• Arch Oncology: lead

Study Sites (6)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Medical College of Wisconsin and Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Andrejeva G, Capoccia BJ, Hiebsch RR, Donio MJ, Darwech IM, Puro RJ, Pereira DS. Novel SIRPalpha Antibodies That Induce Single-Agent Phagocytosis of Tumor Cells while Preserving T Cells. J Immunol. 2021 Feb 15;206(4):712-721. doi: 10.4049/jimmunol.2001019. Epub 2021 Jan 11.

  PMID: 33431660 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ben Oshrine, MD

  Sr Medical Director, Arch Oncology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 Part 1: Up to 4 dose escalation cohorts will be enrolled; each cohort will initially recruit 3 patients to receive AO-176 monotherapy in a standard 3+3 design; the cohort will be expanded in the event of a DLT. Once the RP2D has been identified, an expansion cohort will be enrolled to evaluate AO-176 at the RP2D in combination with dexamethasone (DEX). Phase 1 Part 2: Dose escalation cohorts will evaluate AO-176 in combination with DEX and bortezomib (BORT) to determine the RP2D of AO-176 + DEX + BORT in a standard 3+3 design; the cohort will be expanded in the event of a DLT. Phase 2: Up to 48 patients will be enrolled to evaluate the preliminary efficacy of AO-176 + DEX + BORT using a Simon 2-stage design.

Study Record Dates

• First Submitted: June 17, 2020
• First Posted: June 24, 2020
• Study Start: November 30, 2020
• Primary Completion: August 5, 2022
• Study Completion: November 14, 2022
• Last Updated: August 22, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)