Study of ORIC-533 in Relapsed or Refractory Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT05227144
• Recruitment Status: Recruiting
• First Posted: February 7, 2022
• Last Update Posted: September 21, 2023
• Sponsor: ORIC Pharmaceuticals
• Information provided by (Responsible Party): ORIC Pharmaceuticals

Study Description

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

Condition or disease	Intervention/treatment	Phase
Relapsed or Refractory Multiple Myeloma	Drug: ORIC-533	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Interval 3+3 dose escalation design, followed by dose expansion
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Phase 1b Study of ORIC-533 in Patients With Relapsed or Refractory Multiple Myeloma
• Actual Study Start Date: January 6, 2022
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: June 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation; ORIC-533 dosed orally, once per day of each consecutive 28-day cycle.	Drug: ORIC-533; ORIC-533 once daily in consecutive 28-day cycles
Experimental: Dose Expansion; RP2D dose	Drug: ORIC-533; ORIC-533 once daily in consecutive 28-day cycles

Outcome Measures

Primary Outcome Measures :

1. Recommended Phase 2 Dose (RP2D) [ Time Frame: 12 months ]
   RP2D as determined by interval 3+3 dose escalation design
2. Number of participants with adverse events [ Time Frame: 36 months ]
   Safety and tolerability of ORIC-533
3. Number of participants with abnormal laboratory [ Time Frame: 36 months ]
   Safety and tolerability of ORIC-533

Secondary Outcome Measures :

1. Maximum plasma concentration (Cmax) [ Time Frame: 28 Days ]
   PK of ORIC-533
2. Area under the curve last concentration (AUClast) [ Time Frame: 28 Days ]
   PK of ORIC-533
3. Elimination half-life (t1/2) [ Time Frame: 28 Days ]
   PK of ORIC-533

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 ≥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

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

Contacts and Locations

Contacts

Contact: ORIC Clinical; 650-388-5600; clinical@oricpharma.com

Locations

United States, California

James R. Berenson, MD, Inc.; Completed

West Hollywood, California, United States, 90069

United States, Georgia

Northside Hospital Cancer Institute; Recruiting

Atlanta, Georgia, United States, 30342

Contact: Adriane Strong 404-300-2296 adriane.strong@northside.com

Principal Investigator: Scott Solomon, MD

United States, Massachusetts

Dana-Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Deborah Mailand 617-632-2465 deborahj_mailand@dfci.harvard.edu

Principal Investigator: Omar Nadeem, MD

United States, Minnesota

Mayo Clinical Rochester; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Melanie Thompson 507-284-4726 thompson.melanie@mayo.edu

Principal Investigator: Wilson Gonsalves, MD

United States, New York

Icahn School of Medicine at Mount Sinai; Recruiting

New York, New York, United States, 10029

Contact: Anna Blangiardo 929-989-7229 anna.blangiardo@mssm.edu

Principal Investigator: Cesar Rodriguez Valdes, MD

United States, North Carolina

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

Charlotte, North Carolina, United States, 28203

Contact: Kelly Bumgarner 980-442-2332 kelly.bumgarner@atriumhealth.org

Principal Investigator: Barry Paul, MD

United States, Washington

Swedish Health Services; Recruiting

Seattle, Washington, United States, 98107

Contact: Kory Barrow 206-386-3293 kory.barrow@swedish.org

Principal Investigator: Swathi Namburi, MD

Canada, Ontario

Princess Margaret Cancer Research Center/University Health Network; Recruiting

Toronto, Ontario, Canada

Contact: Hoda Mohamad 416-946-4501 hoda.mohamad@uhn.ca

Principal Investigator: Donna Reece, MD

Sponsors and Collaborators

ORIC Pharmaceuticals

Investigators

• Study Director: Pratik S. Multani, MD; ORIC Pharmaceuticals

More Information

• Responsible Party: ORIC Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05227144
• Other Study ID Numbers: ORIC-533-01
• First Posted: February 7, 2022
• Last Update Posted: September 21, 2023
• Last Verified: September 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ORIC Pharmaceuticals:

CD73

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases