Study of ORIC-533 in Relapsed or Refractory Multiple Myeloma

Overview

About this study

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

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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/?L

- Absolute neutrophil count (ANC) >1000/?L

- 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 (i.e., 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

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/18/23. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Wilson Gonsalves, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions