Study of ORIC-533 in Relapsed or Refractory Multiple Myeloma ORIC-533

What's the purpose of this trial?

The purpose of this study is to establish the Recommended Phase 2 Dose (RP2D), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antimyeloma activity of ORIC-533 in patients with multiple myeloma who have exhausted available treatment options.

This trial is currently open and accepting patients.

What will happen during the trial?

ORIC-533 is a selective, orally bioavailable, small molecule inhibitor of CD73.This is an open-label, uncontrolled, multicenter, dose-finding study to assess the safety and preliminary antimyeloma activity of ORIC-533 in patients with relapsed or refractory multiple myeloma.

After the RP2D has been determined, dose expansion will further evaluate safety and preliminary antimyeloma activity of ORIC-533 in patients with relapsed or refractory multiple myeloma.

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  • 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 ≥60 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 >50,000/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

Exclusion Criteria:

  • 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

Additional Trial Information

Phase 1

Enrollment: 56 patients (estimated)

View More

Published Results

Preliminary Results of the Oral CD73 Inhibitor, Oric-533, in Relapsed/Refractory Multiple Myeloma (RRMM)

December 10, 2023

Results: As of 23 June 2023, 17 patients received ORIC-533 once daily across 4 dose levels (400 mg to 1600 mg). All patients were triple-class refractory, 88% were penta-refractory, and 59% also received prior anti-BCMA/CD3 bispecific therapy or anti-BCMA CAR-T therapy. Overall, ORIC-533 was very well tolerated, with 5 patients experiencing a total of 10 treatment-related adverse events (TRAEs). Fatigue was the only G3 AE and the only TRAE seen in more than 1 patient (1 event each of G3 and G2); all other events seen in 1 patient each, were G1 or G2 in severity, and of no specific system organ class. No dose limiting toxicities, no Grade ≥4 TRAEs, and no treatment-related serious adverse events have been observed. PK showed increased exposure with dose with a plasma half-life of ~24 hrs. Soluble CD73 enzymatic activity was nearly completely inhibited by C1D15 in serum of all patients across all dose levels, while the largest relative suppression in surface CD73 activity in BM cells was observed at the highest dose level. There was also evidence for increases in the abundance of circulating NK and CD8+ T cells after 1 treatment cycle, with preliminary evidence of enhanced CD8+ T-cell activation at the highest dose levels tested in both peripheral blood and BM. In addition, early evidence of single agent clinical activity was observed.

Conclusions: ORIC-533 has demonstrated an acceptable safety profile and preliminary evidence of immune activation in a heavily pretreated RRMM patient population. Enrollment is ongoing and updated data will be presented.

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.


Northside Hospital (Atlanta)

Atlanta, GA

Open and Accepting


Dana-Farber Cancer Institute (Main)

Boston, MA

Open and Accepting


Mayo Clinic (Rochester)

Rochester, MN

Open and Accepting

New York

Mount Sinai Hospital Tisch Cancer Institute

New York, NY

Open and Accepting

North Carolina

Carolinas Medical Center

Charlotte, NC

Open and Accepting


Swedish Medical Center (Ballard Campus)

Seattle, WA

Open and Accepting
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