IRB Study Number 24-791
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
The primary objective is to evaluate the efficacy, safety, and tolerability of ABBV-383 administered as monotherapy in adult subjects with RRMM who have received at least 2 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 mAb.
Inclusion Criteria
Consent
Subjects must voluntarily sign and date an informed consent, approved by an IEC/IRB, prior to the initiation of any screening or study-specific procedures.
Subject must accept to be treated with one of the pre-specified SAT, based on Investigator's choice of local standard of care.
Subjects enrolled in the Investigator's choice SAT arm of the trial must be registered and must comply with all local requirements of the REMS program or equivalent, as applicable.
Subject must consent to a fresh pretreatment bone marrow tumor aspirate and biopsy or has adequate archival bone marrow tumor tissue that was collected within 12 weeks prior to first dose and without intervening treatment (bone marrow core biopsy should be collected, unless not recommended per institutional guidelines).
Are willing and able to comply with procedures required in this protocol.
Subjects must not be incarcerated and must be freely willing and able to provide informed consent (e.g., adults under legal protection measure [e.g., under guardianship/curatorship] or unable to express their consent and select adults under psychiatric care). Investigator's discretion should be applied.
Demographic and Laboratory Assessments
Adult individuals ≥ 18 years old.
ECOG performance status of ≤ 2.
Laboratory values meeting the following criteria within 2 weeks prior to the first dose of study drug:
ANC ≥ 1,000/mm3; platelets: ≥ 50,000/mm3; and hemoglobin ≥ 8.0 g/dL. Transfusion and/or growth factor support is permitted prior to assessment, but neutrophils, platelets, and hemoglobin must be stable for at least 72 hours after transfusion and/or growth factor administration prior to Screening for the subject to be eligible;
AST and ALT ≤ 3 × ULN;
Total bilirubin ≤ 1.5 × ULN (subjects with documented Gilbert's syndrome must have bilirubin ≤ 3.0 × ULN);
eGFR ≥ 30 mL/min as estimated by the MDRD formula;
Serum calcium corrected for albumin ≤ 14.0 mg/dL.
Disease/Condition Activity
- Diagnosis of relapsed and/or refractory MM during or after the subject's last treatment:
Relapsed defined as previously treated myeloma that progresses and requires initiation of salvage therapy;
Refractory defined as disease that is nonresponsive (failure to achieve minimal response) while on last therapy, or progresses within 60 days of last therapy;
Subjects receiving CAR-T cell therapy as their last line of treatment must have documented PD prior to enrollment.
- Subject must have measurable disease within 28 days prior to randomization, defined as at least 1 of the following:
Serum M-protein ≥ 0.5 g/dL (≥ 5 g/L);
Urine M-protein ≥ 200 mg/24 hours;
In subjects without measurable serum or urine M-protein, serum FLC ≥ 100 mg/L (10 mg/dL) (involved light chain) and an abnormal serum kappa lambda ratio. Subject History
Subject must have received at least 2 or more lines of therapy, including exposure to a PI, an IMiD, and an anti-CD38 mAb.
Subject with known HIV will be permitted provided that the subject has an undetectable HIV viral load by standard clinical assays on antiretroviral medication (HAART) and is able to tolerate study treatment per Investigator's judgement.
Note: HIV testing is not required at Screening, unless required per local guidelines or institutional standards.
- Subject must be eligible to receive the Investigator's choice SAT based on approved prescribing information, previous MM treatment history, and institutional guidelines.
Contraception
- Pregnancy testing in female subjects of childbearing potential:
Subjects must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at baseline prior to the first dose of study drug.
Subjects with a borderline serum pregnancy test at Screening must have absence of clinical suspicion of pregnancy or other pathological causes of borderline results and a serum pregnancy test ≥ 3 days later to document continued lack of a positive result (unless prohibited by local requirements).
Subjects with a urine pregnancy test at Baseline that is borderline or ambiguous must have a serum pregnancy test. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Female subjects of childbearing potential must practice at least 1 protocol-specified method of birth control, from Study Day 1 through at least 90 days after the last dose of study drug. Female subjects of nonchildbearing potential (as defined in Section 5.2) do not need to use birth control.
Female subject who is not pregnant or breastfeeding, and is not considering becoming pregnant, or donating eggs, or breastfeeding from Study Day 1 through 90 days after the last dose of study drug.
Subjects randomized in the Investigator's choice SAT should follow the contraception guidance provided in the local (or applicable) approved label, package insert, SmPC, and/or institutional guidelines, as applicable.
Concomitant Medications
- Subject must be able to safety discontinue any prohibited medications (listed in Section 5.4) 5 half-lives or 30 days (whichever is shorter) prior to initial study drug administration. Subjects must have consented for the study prior to discontinuing any prohibited medications for the purpose of meeting study eligibility.
Exclusion Criteria
Subject History
History of significant cardiovascular or pericardial disease, including uncontrolled angina, arrhythmia, recent myocardial infarction within 6 months of first dose, Class ≥ 3 New York Heart Association congestive heart failure.
History of clinically significant conditions such as but not limited to the following: neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, pulmonary, or hepatic disease within the last 6 months that would adversely affect the subject's participation in the study.
History of any malignancy within the past 3 years with the following exceptions:
Adequately treated in situ carcinoma of the cervix uteri or the breast;
Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
Prostate cancer Gleason Grade 6 or lower AND with stable PSA levels on or off treatment;
Previous malignancy with no evidence of disease confirmed and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study.
Have received BCMA-targeted therapy.
Known central nervous system involvement of MM.
History of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months.
Known allergies, hypersensitivities, or intolerance to constituents of the study drug (and its excipients) or derivatives.
Evidence of active hepatitis B (HbsAg positive) infection based on screening blood testing.
Subjects with resolved infection (HbsAg negative, but antiHBc or antiHBs positive) must be screened using real-time PCR of HBV DNA. Those with positive PCR will be excluded.
Exception: Subjects with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
Japan sites only: Subjects enrolled at study sites will be tested for HBsAg and if negative, must have HBcAb and HBsAb tested. Cases negative for HBsAg, positive for HBsAb or HBcAb, and HBV DNA < 20 IU/mL should be monitored as described in Guidelines for the prevention of HBV reactivation in patients receiving immunosuppressive therapy or chemotherapy.
- Evidence of active hepatitis C infection based on screening blood testing.
Subject may not be seropositive for hepatitis C, except in the setting of a sustained virologic
response, defined as aviremia at least 12 weeks after completion of antiviral therapy.
- Known active SARS-CoV-2 infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection, the subject must have a negative molecular (e.g., PCR) test or 2 negative antigen test results at least 24 hours apart. Note: SARS CoV-2 diagnostic test should be applied following local requirements/recommendations.
Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and may only rescreen after they meet the following SARS-CoV-2 infection viral clearance criteria:
At least 10 days since the first positive test result have passed in asymptomatic subjects or at least 10 days since recovery, defined as resolution of fever without use of antipyretics and improvement in symptoms.
- Any of the following conditions:
Non-secretory MM;
Active plasma cell leukemia i.e., either 20% of peripheral white blood cells or > 2.0 × 109/L circulating plasma cells by standard differential;
Waldenstrom's macroglobulinemia;
Light chain amyloidosis;
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes);
Major surgery within 4 weeks prior to first dose or planned study participation; or
Acute infections within 14 days prior to first dose of study drug requiring therapy (antibiotic, antifungal, or antiviral).
Concomitant Medications
Subject treated with any investigational drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study drug.
Subject has received peripheral autologous SCT within 12 weeks, or an allogenic SCT within 1 year of the first dose of study drug treatment.
Subject has received any anti-cancer therapy (including radiation, chemotherapy, biologics, cellular therapies, and/or steroids at doses > 20 mg dexamethasone or equivalent) or undergone a major surgical procedure within 30 days, or within 5 half-lives of an anticancer drug, prior to the first dose of study treatment, whichever is shorter.
Low dose corticosteroids (prednisone ≤ 10 mg or equivalent) are allowed. Additionally, short courses of higher dose corticosteroids (prednisone > 10 mg or equivalent) for indications other than the treatment of multiple myeloma may be administered as clinically indicated per Investigator's discretion.
- Subject has received any live vaccine within 4 weeks prior to the first dose of study drug, or expected need of live vaccination during study participation including at least 4 weeks after the last dose of study drug.
SAT-Specific Exclusion Criteria (not applicable to China safety lead-in and PK cohort)
Subject is not eligible if they have received carfilzomib, elotuzumab, and selinexor.
Subject is not eligible to receive Kd if subject has received prior carfilzomib therapy.
Subject is not eligible to received SVd if:
Subject has received prior selinexor therapy;
Prior PI treatment is allowed provided that subject achieved ≥ PR and > 6 months has elapsed since last PI, with no history of discontinuation due to ≥ Grade 3 toxicity.
- Subject is not eligible to receive EloPd if subject has received prior elotuzumab or pomalidomide therapy.
