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

What's the purpose of this trial?

This study is a first-in-human, Phase 1/2, open label study that will evaluate safety and efficacy of ISB 1442 in relapsed/refractory multiple myeloma (R/R MM).

This trial is currently open and accepting patients.


What will happen during the trial?

The study will be conducted in two phases:

Phase 1: Dose escalation in R/R MM
Phase 2: Dose expansions in select R/R MM

Cohort A: R/R MM

Cohort B: R/R MM Post-T-Cell Directed Therapy Participants will be treated at escalating dose levels in Phase 1 (dose-escalation phase) of the study. Once the safety of ISB 1442 is confirmed and a Recommended Phase 2 Dose (RP2D) is established in Phase 1 for a given indication, Phase 2 will be initiated for that indication.
Participants will receive ISB 1442, until disease progression, unacceptable toxicity, or any criterion for stopping the study drug or withdrawal from the trial occurs.

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  • Male or female patients aged 18 years or older.
  • 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
  • Phase 1: Patients with pathologically confirmed multiple myeloma (MM) who have progressed on or after standard therapy (relapsed/refractory [R/R] patients):
    • 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 ).
  • Must have measurable M-protein (serum and/or 24-hr urine, or serum free light chains).
  • Phase 2: Patients with pathologically confirmed MM who have progressed on or after standard therapy (R/R patients):
    • Cohort A: R/R MM
      • 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;
      • 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
      • 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.
      • 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
  • Have a body weight ≥ 40.0 kg at screening.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less.
  • Have life expectancy of at least 3 months (from date of informed consent signing).
  • Have adequate organ function, including:
    • 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.
    • Estimated creatinine clearance ≥45 mL/min as calculated using the Cockcroft-Gault formula or 24-hour urine collection.
  • Left ventricular ejection fraction (LVEF) ≥45% as assessed by echocardiogram (ECHO) or multiple gated acquisition (MUGA) scan.

Exclusion Criteria:

  • Participants with relapsed disease where relapse is characterized only by minimal residual disease parameters (i.e., minimal residual disease positive).
  • Participants with MM with disease where the only measurable parameter is plasmacytoma.
  • 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.
  • Received autologous stem cell transplantation within 12 weeks of C1D1.
  • 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.
  • 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.
  • Active malignant central nervous system involvement
  • Known to be refractory to platelet or RBC transfusions
  • Known severe allergic or anaphylactic reactions to human recombinant proteins or excipients used in the ISB 1442 formulation.
  • QTc interval > 480 msec at screening using Fredericia's QT correction formula.

Additional Trial Information

Phase 1/2

Enrollment: 121 patients (estimated)

View More

Published Results

Initial Dose Escalation of ISB 1442, a Novel CD38 Biparatopic x CD47 Bispecific Antibody, in Patients with Relapsed / Refractory Multiple Myeloma (RRMM)

December 11, 2023

Results: As of July 18, 2023, based on preliminary data from ongoing clinical database, 10 subjects had received once weekly SC injections of ISB 1442 in 4 dose-escalation groups from 6 mg to 150 mg. The majority were male (60%) and white (90%). The median age was 67 years (range 57-79). The median number of prior anti-myeloma lines of therapy was 6 (range 3-7); 70% were exposed to 5 drugs (2PIs, 2IMiDs, and CD38). The median number of ISB 1442 cycles was 1(range 1-2). Eight subjects (80%) experienced treatment-related adverse events (TRAEs), all were grade 1 or 2: cytokine release syndrome (CRS) (50%), injection site reactions (injection site erythema 20%, injection site bruising 10%), anemia (10%, 1 subject, grade 2) (Table 1). No grade 5 TRAE was observed. Following QW SC injection, ISB 1442 was slowly absorbed into the systemic circulation with Tmax generally occurring on day 2 of dosing. The ISB 1442 serum concentrations generally remained quantifiable over the entire dosing duration from 20 mg and above. The available PK data suggest an approximately dose-linear increase in serum concentration up to DL 3 (60 mg), followed by a supra-proportional increase in serum levels in subjects treated at DL 4 (150 mg). To date, 5 subjects treated at DL4 (150 mg) have experienced clinical symptoms of CRS (Grade 1-2) following the first dose of ISB 1442. Assessment of a panel of 63 soluble factors (including multiple cytokines, chemokines and growth factors) in the peripheral blood revealed that several subjects at DL3-4 exhibited transient increases (>10-fold) in macrophage inflammatory protein-1b (MIP-1b/CCL4) within 24h after treatment with ISB 1442, consistent with a macrophage-associated mechanism of action.

Conclusions: Treatment with ISB 1442 was well tolerated at the dose levels evaluated. The observed clinical CRS events were moderate and potentially related to macrophage activation following ISB 1442 administration. Updated clinical, biomarker and PK data will be presented for this ongoing study.

Trial Links

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Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

Florida

Illinois

University of Chicago Medicine Comprehensive Cancer Center

Chicago, IL

Not Yet Accepting

Michigan

Barbara Ann Karmanos Cancer Institute Wayne State University

Detroit, MI

Not Yet Accepting

Missouri

Alvin J. Siteman Cancer Center Washington University Medical Campus

St. Louis, MO

Open and Accepting

New York

Weill Cornell

New York, NY

Not Yet Accepting

Wisconsin

Medical College of Wisconsin Froedtert Hospital

Milwaukee, WI

Open and Accepting
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