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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04445701
• Other study ID #: AO-176-102
• Status: Completed
• Phase: Phase 1/Phase 2
• 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
• 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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

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