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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04445701
Other study ID # AO-176-102
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date November 30, 2020
Est. completion date November 14, 2022

Study information

Verified date August 2023
Source Arch Oncology
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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).


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.


Recruitment information / eligibility

Status Completed
Enrollment 10
Est. completion date November 14, 2022
Est. primary completion date August 5, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
AO-176
Humanized monoclonal antibody (mAb) targeting CD47
AO-176 + Dex
Humanized mAb targeting CD47 plus dexamethasone
AO-176 + Dex + Bort
Humanized mAb targeting CD47 plus dexamethasone plus bortezomib

Locations

Country Name City State
United States Emory University Atlanta Georgia
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Mayo Clinic Jacksonville Florida
United States Medical College of Wisconsin and Froedtert Hospital Milwaukee Wisconsin
United States Mayo Clinic Phoenix Arizona
United States Mayo Clinic Rochester Minnesota

Sponsors (1)

Lead Sponsor Collaborator
Arch Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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 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 12 months
Secondary 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 12 months
Secondary 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 12 months
Secondary 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 12 months
Secondary Phase 1: Overall survival (OS) of single agent AO-176 Evaluate the clinical activity of single agent AO-176 based on OS 12 months
Secondary 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 12 months
Secondary 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 12 months
Secondary 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 12 months
Secondary Phase 2: OS of AO-176 + DEX + BORT Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on OS 12 months
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