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

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

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).

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.

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.