Phase 1/2 Study of ISB 1442 in Relapsed/Refractory Multiple Myeloma

This is an interventional treatment trial for Relapsed/Refractory Multiple Myeloma focused on measuring Open-label, dose-escalation, dose-expansion, ISB 1442, relapsed/refractory multiple myeloma Read More

Inclusion Criteria:

1. Male or female patients aged 18 years or older.
2. Be willing and able to provide written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act of 1996 [HIPAA]) prior to any protocol related procedures, including screening evaluations

3. Phase 1: Patients with pathologically confirmed multiple myeloma (MM) who have progressed on or after standard therapy (relapsed/refractory [R/R] patients):

   1. Must have received at least 3 prior lines of therapy, including PIs, IMiDs, and anti CD38 therapies either in combination or as a single agent; and must not be candidates for regimens known to provide clinical benefit. (Note: Patients in Australia may have received any of the therapies including PIs, IMiDs, and anti CD38 therapies either in combination or as a single agent; and must not be candidates for regimens known to provide clinical benefit ).
   2. Must have measurable M-protein (serum and/or 24-hr urine, or serum free light chains).

4. Phase 2: Patients with pathologically confirmed MM who have progressed on or after standard therapy (R/R patients):

   Cohort A: R/R MM

   1. Must have received at least 3 prior lines of therapy, including PIs, IMiDs, and anti CD38 therapies either in combination or as a single agent;

   2. Must have measurable disease defined by at least 1 of the following abnormalities (as per IMWG criteria):

      • Serum M-protein ≥ 0.5 g/L (IgA ≥ 0.5 g/L), or
      • Urine light-chain (M-protein) of ≥ 200 mg/24 hours, or
      • Serum free light chain (sFLC) assay: involved free light chain (FLC) level ≥ 10 mg/dL provided sFLC ratio is abnormal.

   Cohort B: R/R MM Post-T-Cell Directed Therapy

   1. Must have received at least 3 prior lines of therapy, including PIs, IMiDs and anti-CD38 therapies either in combination or as a single agent; and have relapsed and/or be refractory to a T-cell directed therapy including cellular therapies or T cell engagers.

   2. Must have measurable disease defined by at least 1 of the following abnormalities (as per IMWG criteria):

      • Serum M-protein ≥ 0.5 g/L (IgA ≥ 0.5 g/L), or
      • Urine light-chain (M-protein) of ≥ 200 mg/24 hours, or
      • sFLC assay: involved FLC level ≥ 10 mg/dL provided sFLC ratio is abnormal
5. Have a body weight ≥ 40.0 kg at screening.
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less.
7. Have life expectancy of at least 3 months (from date of informed consent signing).

8. Have adequate organ function, including:

   1. Aspartate aminotransferase (AST, GOT) and alanine aminotransferase (ALT, GPT) ≤3.0 × ULN; bilirubin ≤1.5 × ULN. Patients with Gilbert's syndrome may have a bilirubin level >1.5 × ULN, per discussion between the Investigator and medical monitor.
   2. Estimated creatinine clearance ≥45 mL/min as calculated using the Cockcroft-Gault formula or 24-hour urine collection.
9. Left ventricular ejection fraction (LVEF) ≥45% as assessed by echocardiogram (ECHO) or multiple gated acquisition (MUGA) scan.

Exclusion Criteria:

1. Participants with relapsed disease where relapse is characterized only by minimal residual disease parameters (i.e., minimal residual disease positive).
2. Participants with MM with disease where the only measurable parameter is plasmacytoma.
3. Received treatment with anti-CD38 antibodies or CD47 targeted therapies within 1 month of C1D1; systemic anticancer treatments within 14 days before the first dose of study drug (C1D1) or any investigational products within 5 half-lives of C1D1, whichever is appropriate to last therapy received. (eg, non-IMP IMiD, proteasome inhibitor could be considered to be eligible if there is at least 14 days after last dose before C1D1. Note: Treatment with a single course of glucocorticoids is allowed (maximum dose of corticosteroids should not exceed the equivalent of 160 mg [for example, 40 mg/d for 4 days] of dexamethasone). Hormonal therapy for prostate cancer or breast cancer (as adjuvant treatment), and treatment with bisphosphonates and receptor activator of nuclear factor kappa-Β ligand inhibitors are allowed.
4. Received autologous stem cell transplantation within 12 weeks of C1D1.
5. Current participation in another interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device for disease under study) within 4 weeks of C1D1 and throughout the duration of this trial.
6. Prior radiation therapy within 14 days of C1D1; or prior irradiation to > 25% of the bone marrow. Note: Prophylactic localized ("spot") radiation for areas of pain is allowed.
7. Active malignant central nervous system involvement
8. Known to be refractory to platelet or RBC transfusions
9. Known severe allergic or anaphylactic reactions to human recombinant proteins or excipients used in the ISB 1442 formulation.
10. QTc interval > 480 msec at screening using Fredericia's QT correction formula.