Clinical Trials

Inclusion Criteria:

• At least 18 years of age at the time of signing the informed consent.
• Documented 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 (IMIDs), a proteasome inhibitor (PI), and an anti-CD38 antibody, with documented disease progression.
• Agreement and ability to undergo on-study biopsies, through a procedure that is deemed to be clinically feasible and not carry significant risk.
• 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 chain (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 m^2 (calculated using the Cockcroft-Gault equation (Cockcroft and Gault 1976). A 24-hour urine collection for creatinine clearance may be used at the investigator’s discretion.
  • 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 (platelet transfusions not permitted within 7 days of qualifying lab result).
  • Absolute neutrophil count (ANC) > 1000/μL (G-CSF not permitted within 7 days of qualifying lab result).
  • Left ventricular ejection fraction (LVEF) > 45% as assessed by echocardiogram (ECHO) or multiple gated acquisition (MUGA). ECHO/MUGA results performed within 6 months before screening and at least 28 days after the last cancer treatment may be acceptable if the study participant has not received any treatment with cardiotoxicity risks.
  • Baseline oxygen saturation > 92% on room air.
• Male: must agree to the following during the treatment period and for at least 3 months after the last dose of study treatment:
  • Refrain from donating sperm; AND either
  • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent; OR
  • Use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant;
  • Female: not pregnant, breastfeeding, and at least one of the following conditions apply:
  • Is not a woman of childbearing potential (WOCBP); OR
  • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year) with low user dependency during the treatment period and for at least 3 months after the last dose of study treatment. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment;
  •  A WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours before the first dose of study treatment
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

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.
• Treatment with the following therapies within the stated time frames prior to initiation of ORIC-533 therapy (ie, wash-out periods for different therapies):
  • Previous cytotoxic therapies, including cytotoxic investigational agents (approved for other indications but not for MM) within 21 days (42 days for nitrosoureas);
  • The use of live vaccines within 28 days;
  • IMIDs or PI within 14 days;
  • Prior anti-BCMA or CAR T therapy within 28 days;
  • Prior peripheral stem cell transplant within 12 weeks;
  • Prior allogeneic stem cell transplantation with active graft-versus-host-disease.
• Receiving any investigational treatment with a novel investigational agent (ie, no approved indication) within 28 days prior to the first dose of study drug:
  • Clinical trials of FDA approved agents used for MM may have washout period as outlined above.
• Not recovered or stabilized from all toxicities from prior anticancer therapies to and/or radiotherapy 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.
• 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.

Eligibility last updated 9/23/21. Questions regarding updates should be directed to the study team contact.