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).
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
Interventions
| Drug | Synonyms | Arms |
|---|
| AO-176 | | AO-176 Dose Escalation Monotherapy |
| AO-176 + Dex | | AO-176 + DEX Expansion Cohort |
| AO-176 + Dex + Bort | | AO-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
| Name | Type | Description | Interventions |
|---|
| AO-176 Dose Escalation Monotherapy | Experimental | 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. | |
| AO-176 + DEX Expansion Cohort | Experimental | Once the monotherapy RP2D has been established, an expansion cohort of AO-176 + dexamethasone will be enrolled. | |
| AO-176 + DEX + BORT Dose Escalation | Experimental | 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. | |
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: | Recruiting |
| Lead Sponsor: | Arch Oncology |
Trial Keywords
- AO-176
- CD47
- Immunotherapy
- Monoclonal antibody
Last Updated
July 7, 2021
