Clinical Trials

Inclusion Criteria: 

Consent

• Subjects or their legally authorized representative 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 is capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent.
• Subject consents to a fresh pretreatment bone marrow tumor biopsy or has adequate archival bone marrow tumor tissue that was collected within 12 weeks prior to screening and without intervening treatment.

Demographic and Laboratory Assessments

• Adult individuals, male or female, ≥ 18 years old at the time of screening.
• Eastern Cooperative Oncology Group (ECOG) performance of ≤ 2.
• Subjects must meet the following laboratory parameters within the screening period prior to the first dose of study drug:
  • Subject must have adequate bone marrow function, defined as: ANC ≥ 1000/mm^3 ; platelets ≥ 50,000/mm^3 ; 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 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 × ULN);
  • Estimated glomerular filtration rate ≥ 30 mL/min as estimated by the Modification of Diet in Renal Disease (MDRD) formula.

Disease/Condition Activity

• Subject has confirmed evidence of R/R measurable MM from the immediate prior antimyeloma therapy.
• Subject must have received a minimum of 1 prior line of therapy, including exposure to at least one of the following agents: a PI, IMiD, or an anti-CD38 mAb.
• Subject must have measurable disease within 28 days of enrollment, defined as at least 1 of the following:
  • Serum monoclonal paraprotein (M-protein) level ≥ 0.5 g/dL (≥ 5 g/L);
  • Urine M-protein ≥ 200 mg/24 hours;
  • Serum Free light chain ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio only for subjects without measurable serum or urine M-protein.
• Subject must be naïve to treatment with ABBV-383.

Contraception

• For all female subjects of child-bearing potential; 2 negative results for pregnancy tests prior to initiating therapy:
  • The first test (serum) should be performed during the Screening period prior to first ABBV383 administration;
  • The second test (Serum or urine [minimum sensitivity of 25 IU/I for urine]) should be performed within 24 hours prior to first dose of ABBV-383 administration;
  • Female subjects who are not of childbearing potential at Screening do not require pregnancy testing (see Section 5.2 for details).
• Female subjects of childbearing potential must practice at least 2 protocol-specified methods of birth control, that is effective from 28 days prior to Study Day 1 through at least 90 days after the last dose of study drug. Female subjects of non-childbearing potential do not need to use birth control:
  • Note: Females of non-childbearing potential are defined as a female who is not pregnant or breastfeeding, and is not considering becoming pregnant, donating eggs, or breastfeeding from Study Day 1 through 90 days after the last dose of ABBV-383.

Other

• Subjects with HIV will be permitted provided that the subject has an undetectable HIV viral load by standard clinical assays on antiretroviral medication (highly active antiretroviral therapy [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.

Exclusion Criteria

Disease/Condition Activity

• Subject has received BCMAxCD3 bispecific antibody.

Subject History

• Subject has clinically significant conditions such as but not limited to the following: renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, pulmonary, or hepatic disease within the last 6 months that in Investigator's opinion, would adversely affect the subject's participation in the study.
• Subject has known central nervous system involvement of MM.
• Subject has history of other active malignancies 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 Prostate Specific Antigen (PSA) on or off hormonal therapy;
  • 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.
• Subject has 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. For Israel, and other countries based on local requirements/regulations, subjects with positive antiHBc, with or without positive HBV DNA 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 hepatitis B core antibody (HBcAb) and hepatitis B surface antibody (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.
• Subject has 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.
• Subject has 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 result or 2 negative-antigen test results at least 24 hours apart:
  • Note: SARS-CoV-2 diagnostic tests should be applied following local requirements/ recommendations.
• Subjects who do meet SARS-CoV-2 infection exclusion criteria must be screen failed and may only rescreen for the study after they meet the following SARS-CoV-2 infection viral clearance criteria:
  • At least 10 days since first positive test result have passed in asymptomatic patients or at least 10 days since recovery, defined as resolution of fever without use of antipyretics and improvement in symptoms.
• Subject has history of significant cardiovascular or pericardial disease, including uncontrolled angina, arrhythmia, recent myocardial infarction within 12 weeks of first dose, congestive heart failure cardiovascular disability status of New York Heart Association Class ≥ 3.
• Subject has known history of clinically significant (per investigator's judgment) alcohol or drug abuse within the last 6 months.
• Subject has any of the following conditions:
  • Non secretory MM;
  • Active plasma cell leukemia i.e., either 20% of peripheral white blood cells or > 2.0 × 10^9 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 28 days prior to first dose or planned study participation;
  • Acute infections within 14 days prior to first dose of study drug requiring therapy (antibiotic, antifungal, or antiviral);
  • JAPAN only: History of or evidence of current interstitial lung disease. 
• Subject has known allergic reaction, significant sensitivity, or intolerance to constituents of the study drug (and its excipients) and/or other products in the same class.

Concomitant Medications 12. Subjects have been treated with any investigational drug within 30 days or 5 half-lives of the drug (whichever is longer), of enrollment.

• Subjects have received a peripheral autologous stem cell transplant within 12 weeks, or an allogeneic stem cell transplant within 1 year of the first dose of study drug treatment.
• Subjects have received any therapy to treat cancer (including radiation, chemotherapy, biologics, cellular therapies, and/or steroids) within 30 days, or within 5 half-lives of an anticancer drug, prior to the first dose of study treatment, whichever is shorter.
• Subject have received any live vaccine within 30 days prior to the first dose of study drug, or expected need of live vaccination during study participation including at least 90 days after the last dose of study drug.

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

Eligibility last updated 12/8/23. Questions regarding updates should be directed to the study team contact.