Study of AO-176 as Monotherapy and in Combination With Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma
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ClinicalTrials.gov Identifier: NCT04445701 |
Recruitment Status :
Recruiting
First Posted : June 24, 2020
Last Update Posted : January 13, 2021
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Condition or disease | Intervention/treatment | Phase |
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Multiple Myeloma | Drug: AO-176 Drug: AO-176 + Dex Drug: AO-176 + Dex + Bort | Phase 1 Phase 2 |
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 (Clinical Trial) |
Estimated Enrollment : | 102 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Intervention Model Description: | 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. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1/2, Dose Escalation Safety and Tolerability Study of AO-176 as Monotherapy and in Combination With Bortezomib and Dexamethasone in Adults With Relapsed or Refractory Multiple Myeloma |
Actual Study Start Date : | November 30, 2020 |
Estimated Primary Completion Date : | March 2023 |
Estimated Study Completion Date : | March 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: AO-176 Dose Escalation Monotherapy
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.
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Drug: AO-176
Humanized monoclonal antibody (mAb) targeting CD47 |
Experimental: AO-176 + DEX Expansion Cohort
Once the monotherapy RP2D has been established, an expansion cohort of AO-176 + dexamethasone will be enrolled.
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Drug: AO-176 + Dex
Humanized mAb targeting CD47 plus dexamethasone |
Experimental: AO-176 + DEX + BORT Dose Escalation
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.
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Drug: AO-176 + Dex + Bort
Humanized mAb targeting CD47 plus dexamethasone plus bortezomib |
- 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 [ Time Frame: 12 months ]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
- Phase 2: Objective response rate (ORR) of AO-176 + DEX + BORT [ Time Frame: 12 months ]Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on ORR using International Myeloma Working Group (IMWG) uniform response criteria
- Phase 1: ORR of single agent AO-176 [ Time Frame: 12 months ]Evaluate the clinical activity of single agent AO-176 based on ORR using IMWG uniform response criteria
- Phase 1: Duration of response (DOR) of single agent AO-176 [ Time Frame: 12 months ]Evaluate the clinical activity of single agent AO-176 based on DOR using IMWG uniform response criteria
- Phase 1: Disease control rate (DCR) of single agent AO-176 [ Time Frame: 12 months ]Evaluate the clinical activity of single agent AO-176 based on DCR using IMWG uniform response criteria
- Phase 1: Progression-free survival (PFS) of single agent AO-176 [ Time Frame: 12 months ]Evaluate the clinical activity of single agent AO-176 based on PFS using IMWG uniform response criteria
- Phase 1: Overall survival (OS) of single agent AO-176 [ Time Frame: 12 months ]Evaluate the clinical activity of single agent AO-176 based on OS
- Phase 2: DOR of AO-176 + DEX + BORT [ Time Frame: 12 months ]Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on DOR using IMWG uniform response criteria
- Phase 2: DCR of AO-176 + DEX + BORT [ Time Frame: 12 months ]Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on DCR using IMWG uniform response criteria
- Phase 2: PFS of AO-176 + DEX + BORT [ Time Frame: 12 months ]Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on PFS using IMWG uniform response criteria
- Phase 2: OS of AO-176 + DEX + BORT [ Time Frame: 12 months ]Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on OS

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- 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 0-1
- Resolution of prior therapy-related adverse events
- Minimum of 2 weeks since last dose of cancer therapy or radiotherapy
Key Exclusion Criteria:
- 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04445701
Contact: Kevin Romanko, DPM | 415-671-4028 | kromanko@archoncology.com | |
Contact: Amy Douglas | adouglas@archoncology.com |
United States, Arizona | |
Mayo Clinic | Recruiting |
Phoenix, Arizona, United States, 85054 | |
Principal Investigator: Jeremy Larsen, MD | |
United States, California | |
Stanford University | Not yet recruiting |
Palo Alto, California, United States, 94305 | |
Principal Investigator: Michaela Liedtke, MD | |
United States, Florida | |
Mayo Clinic | Recruiting |
Jacksonville, Florida, United States, 32224 | |
Principal Investigator: Sikander Ailawadhi, MD | |
United States, Georgia | |
Emory University | Not yet recruiting |
Atlanta, Georgia, United States, 30322 | |
Principal Investigator: Ajay Nooka, MD | |
United States, Massachusetts | |
Beth Israel Deaconess Medical Center | Not yet recruiting |
Boston, Massachusetts, United States, 02215 | |
Principal Investigator: Jacalyn Rosenblatt, MD | |
Dana-Farber Cancer Institute | Not yet recruiting |
Boston, Massachusetts, United States, 02215 | |
Principal Investigator: Clifton C Mo, MD | |
United States, Minnesota | |
Mayo Clinic | Recruiting |
Rochester, Minnesota, United States, 55905 | |
Principal Investigator: Morie Gertz, MD | |
United States, Washington | |
Swedish Cancer Institute | Not yet recruiting |
Seattle, Washington, United States, 98104 | |
Principal Investigator: William Bensinger, MD | |
United States, Wisconsin | |
Medical College of Wisconsin and Froedtert Hospital | Recruiting |
Milwaukee, Wisconsin, United States, 53226 | |
Principal Investigator: Parameswaran Hari, MD |
Study Director: | Jackie Walling, MBChB, PhD | Arch Oncology |
Responsible Party: | Arch Oncology |
ClinicalTrials.gov Identifier: | NCT04445701 |
Other Study ID Numbers: |
AO-176-102 |
First Posted: | June 24, 2020 Key Record Dates |
Last Update Posted: | January 13, 2021 |
Last Verified: | January 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
AO-176 CD47 Immunotherapy Monoclonal antibody |
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases |
Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases |