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Multiple MyelomaPhase 1/2NCT04445701

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

A Phase 1/2 study testing AO-176, AO-176 + Dex and AO-176 + Dex + Bort in people with Multiple Myeloma, run by Arch Oncology at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
AO-176, AO-176 + Dex and AO-176 + Dex + Bort
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
6 sitesUnited States
Study dates
30 Nov 2020to 14 Nov 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Emory University

    Atlanta, Georgia, 30322

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • Medical College of Wisconsin and Froedtert Hospital

    Milwaukee, Wisconsin, 53226

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

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

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).

Read the detailed description

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.

Being tested
AO-176, AO-176 + Dex, AO-176 + Dex + Bort
Keywords
AO-176, CD47, Immunotherapy, Monoclonal antibody
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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

Study groups in NCT04445701
Study groupRoleWhat they receive
AO-176 Dose Escalation MonotherapyExperimentalThe 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.
Receives: Drug: AO-176
AO-176 + DEX Expansion CohortExperimentalOnce the monotherapy RP2D has been established, an expansion cohort of AO-176 + dexamethasone will be enrolled.
Receives: Drug: AO-176 + Dex
AO-176 + DEX + BORT Dose EscalationExperimentalFollowing 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.
Receives: Drug: AO-176 + Dex + Bort

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 12 months

  2. 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

    Measured: 12 months

Secondary outcomes (9)

  1. 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

    Measured: 12 months

  2. 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

    Measured: 12 months

  3. 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

    Measured: 12 months

  4. 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

    Measured: 12 months

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

    Evaluate the clinical activity of single agent AO-176 based on OS

    Measured: 12 months

  6. Phase 2: DOR of AO-176 + DEX + BORT

    Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on DOR using IMWG uniform response criteria

    Measured: 12 months

  7. Phase 2: DCR of AO-176 + DEX + BORT

    Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on DCR using IMWG uniform response criteria

    Measured: 12 months

  8. Phase 2: PFS of AO-176 + DEX + BORT

    Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on PFS using IMWG uniform response criteria

    Measured: 12 months

  9. Phase 2: OS of AO-176 + DEX + BORT

    Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on OS

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jun 2020
  2. Study start30 Nov 2020
  3. Primary completion5 Aug 2022
  4. Study completion14 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
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)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04445701
Sponsor's protocol ID
AO-176-102
Status last verified
Aug 2023
First submitted
17 Jun 2020
Last updated
22 Aug 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33431660

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AO-176, AO-176 + Dex and AO-176 + Dex + Bort in people with Multiple Myeloma, run by Arch Oncology at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04445701, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.

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