Study of ORIC-533 in Relapsed or Refractory Multiple Myeloma

NCT05227144 | Completed Phase 1 FDA Drug

• 1 other identifier: ORIC-533-01
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 8

Brief Summary

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

Conditions

Relapsed or Refractory Multiple Myeloma

Keywords

CD73

Outcome Measures

Primary Outcomes (3)

• Recommended Phase 2 Dose (RP2D)

  RP2D as determined by interval 3+3 dose escalation design

  12 months

• Number of participants with adverse events

  Safety and tolerability of ORIC-533

  36 months

• Number of participants with abnormal laboratory

  Safety and tolerability of ORIC-533

  36 months

Secondary Outcomes (3)

• Maximum plasma concentration (Cmax)

  28 Days

• Area under the curve last concentration (AUClast)

  28 Days

• Elimination half-life (t1/2)

  28 Days

Study Arms (2)

Dose Escalation

EXPERIMENTAL

ORIC-533 dosed orally, once per day of each consecutive 28-day cycle.

Drug: ORIC-533

Dose Expansion

EXPERIMENTAL

RP2D dose

Drug: ORIC-533

Interventions

ORIC-533 DRUG

ORIC-533 once daily in consecutive 28-day cycles

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• ORIC Pharmaceuticals: lead

Study Sites (8)

James R. Berenson, MD, Inc.

West Hollywood, California, 90069, United States

Location

Northside Hospital Cancer Institute

Atlanta, Georgia, 30342, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinical Rochester

Rochester, Minnesota, 55905, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

The Charlotte-Mecklenburg Hospital Authority d/b/a Atrium Health

Charlotte, North Carolina, 28203, United States

Location

Swedish Health Services

Seattle, Washington, 98107, United States

Location

Princess Margaret Cancer Research Center/University Health Network

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Pratik S. Multani, MD

  ORIC Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Interval 3+3 dose escalation design, followed by dose expansion

Study Record Dates

• First Submitted: February 2, 2022
• First Posted: February 7, 2022
• Study Start: January 6, 2022
• Primary Completion: March 3, 2025
• Study Completion: March 3, 2025
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (7)