Clinical Trials /

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

NCT04445701

Description:

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).

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of AO-176 as Monotherapy and in Combination With Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma
  • 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 IDs

  • ORG STUDY ID: AO-176-102
  • NCT ID: NCT04445701

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
AO-176AO-176 Dose Escalation Monotherapy
AO-176 + DexAO-176 + DEX Expansion Cohort
AO-176 + Dex + BortAO-176 + DEX + BORT Dose Escalation

Purpose

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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
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.
  • AO-176
AO-176 + DEX Expansion CohortExperimentalOnce the monotherapy RP2D has been established, an expansion cohort of AO-176 + dexamethasone will be enrolled.
  • 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.
  • AO-176 + Dex + Bort

Eligibility Criteria

        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 0-1

          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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Phase 1: ORR of single agent AO-176
Time Frame:12 months
Safety Issue:
Description:Evaluate the clinical activity of single agent AO-176 based on ORR using IMWG uniform response criteria
Measure:Phase 1: Duration of response (DOR) of single agent AO-176
Time Frame:12 months
Safety Issue:
Description:Evaluate the clinical activity of single agent AO-176 based on DOR using IMWG uniform response criteria
Measure:Phase 1: Disease control rate (DCR) of single agent AO-176
Time Frame:12 months
Safety Issue:
Description:Evaluate the clinical activity of single agent AO-176 based on DCR using IMWG uniform response criteria
Measure:Phase 1: Progression-free survival (PFS) of single agent AO-176
Time Frame:12 months
Safety Issue:
Description:Evaluate the clinical activity of single agent AO-176 based on PFS using IMWG uniform response criteria
Measure:Phase 1: Overall survival (OS) of single agent AO-176
Time Frame:12 months
Safety Issue:
Description:Evaluate the clinical activity of single agent AO-176 based on OS
Measure:Phase 2: DOR of AO-176 + DEX + BORT
Time Frame:12 months
Safety Issue:
Description:Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on DOR using IMWG uniform response criteria
Measure:Phase 2: DCR of AO-176 + DEX + BORT
Time Frame:12 months
Safety Issue:
Description:Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on DCR using IMWG uniform response criteria
Measure:Phase 2: PFS of AO-176 + DEX + BORT
Time Frame:12 months
Safety Issue:
Description:Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on PFS using IMWG uniform response criteria
Measure:Phase 2: OS of AO-176 + DEX + BORT
Time Frame:12 months
Safety Issue:
Description:Evaluate the clinical activity of AO-176 + dexamethasone + bortezomib based on OS

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Arch Oncology

Trial Keywords

  • AO-176
  • CD47
  • Immunotherapy
  • Monoclonal antibody

Last Updated

June 22, 2020