ORIC-533 once daily in consecutive 28-day cycles

* Diagnosis of multiple myeloma (MM) with relapsed or refractory disease according to IMWG Criteria * Refractory to or not eligible for MM treatment regimens known to provide clinical benefit, including but not limited to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, with documented disease progression * Measurable disease at screening, including at least 1 of the criteria below: * Serum M-protein >0.5 g/dL (Patients with IgA myeloma in whom serum M protein is unreliable due to comigration of normal serum proteins may be considered eligible if total IgA >400 mg/dL) * Urine M-protein >200 mg/24 hours * Serum free light chains (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65) * Measurable bone or extramedullary plasmacytoma * ECOG performance status ≤2 * Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as: * Estimated glomerular filtration rate ≥40 mL/min/1.73 m2. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both ≤3 times of upper limit of normal, unless there is suspected disease in the liver, in which case, no limit is set provided serum bilirubin is within eligibility criterion * Total bilirubin <1.5 × upper limit of normal (ULN), except in study participants with Gilbert's syndrome * Platelet count >40,000/μL * Absolute neutrophil count (ANC) >1000/μL * Left ventricular ejection fraction (LVEF) >45% as assessed by echocardiogram (ECHO) or multiple gated acquisition (MUGA) * Baseline oxygen saturation >92% on room air

* Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy * Previous or concurrent plasma cell leukemia, AL amyloidosis, or POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome * Known central nervous system (CNS) involvement * Evidence of hyperviscosity syndrome * Receiving any investigational treatment with a novel investigational agent (ie, no approved indication) within 28 days prior to the first dose of study drug * Not recovered or stabilized from all toxicities from prior anticancer therapies and/or radiotherapy to Grade <2 with the exception of peripheral neuropathy * Major surgery or radiation therapy within 14 days prior to first dose of study drug or incomplete recovery from adverse effects resulting from such procedure * Those who require limited course of radiation for management of bone pain for ≤14 days from initiation of therapy are not excluded * Infection requiring systemic antibiotic therapy or other serious infection within 14 days of starting therapy * Those who are on prophylactic antibiotics only, or on antibiotics and have confirmation of resolution of active infection, are eligible * Daily requirement for corticosteroids (equivalent to >10 mg/day prednisone). Inhalation corticosteroids are exempt from this criterion * Exception: Corticosteroid dose equivalent >10 mg/day prednisone is acceptable if physiological levels require, so long as the dose is stable for at least 7 days prior to initiation of therapy * Lower amounts of corticosteroids that are not part of a daily requirement within 14 days prior to initiating therapy are also acceptable * Known seropositive for active viral infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C virus (HCV). Those who are seropositive because of hepatitis B vaccine are eligible. Patients who are positive for HBV core antibody or HBV surface antigen must have a negative polymerase chain reaction (PCR) result prior to enrollment. Those who are PCR positive will be excluded. * History of class III or IV congestive heart failure or severe non-ischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months of first dose of study drug * QTcF >470 msec * Other concurrent serious uncontrolled medical, psychological, or addictive conditions that, in the opinion of the investigator, may interfere with protocol compliance or contraindicates participation in the study

Princess Margaret Cancer Research Center/University Health Network, Toronto, Ontario – ()