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

Arch Oncology

Status and phase: Completed; Phase 2; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: AO-176; Drug: AO-176 + Dex + Bort; Drug: AO-176 + Dex

Study type: Interventional

Funder types: Industry

Identifiers

NCT04445701

AO-176-102

Details and patient eligibility

About

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).

Full 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.

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 0-2
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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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10 participants in 3 patient groups

AO-176 Dose Escalation Monotherapy

Experimental group

Description:

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.

Treatment:

Drug: AO-176

AO-176 + DEX Expansion Cohort

Experimental group

Description:

Once the monotherapy RP2D has been established, an expansion cohort of AO-176 + dexamethasone will be enrolled.

Treatment:

Drug: AO-176 + Dex

AO-176 + DEX + BORT Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: AO-176 + Dex + Bort