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

A Phase 1/2, First-in-Human, Multicenter, Open-Label, Dose Escalation and Dose-Expansion Study of Single-Agent ISB 1442 in Participants With Relapsed/Refractory Multiple Myeloma

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).

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Drug: ISB 1442 SC injection escalating doses; Drug: ISB 1442 SC injection at RP2D

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 121
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ichnos Sciences Clinical Trials Administrator; Phone Number: (315) 583-1249; Email: clinicaltrials@ichnossciences.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Royal Prince Albert Hospital: Institute of Haematology
      • Contact: Jo Ho, MBBS,D.Phil,FRACP,FRCPA,FFSc; Email: joy.ho1@health.nsw.gov.au
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Recruiting
      • Pindara Private Hospital
      • Contact: Hanlon Sia, MBBS(Adelaide), FRACP, FRCPA; Email: hanlonsia@yahoo.com.au
    • Southport, Queensland, Australia, 4211
      • Recruiting
      • Gold Coast University Hospital
      • Contact: Tara Cochrane, MD; Email: tara.cochrane@health.qld.gov.au
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St. Vincent's Hospital Melbourne
      • Contact: Hang Ai Quach, MD; Email: hang.quach@svha.org.au
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred Hospital-Melbourne
      • Contact: Andrew Spencer, MBBS FRACP FRCPA DM; Email: andrew.spencer@monash.edu
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • One Clinical Research PTY LTD
      • Contact: Peter Tan, MBBS(Hons),MPhil,FRACP,FRCPA; Email: peter.tan@oneclinicalresearch.com.au
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami - Sylvester Comprehensive Cancer Center
      • Contact: Dickran G. Kazandjian, MD; Email: dkazandjian@miami.edu
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Not yet recruiting
      • The University of Chicago Medical Center (UCMC) Duchossois Center for Advanced Medicine (DCAM)
      • Contact: Benjamin Derman, MD; Email: bderman@bsd.uchicago.edu
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Not yet recruiting
      • Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main Campus
      • Contact: Jeffrey Zonder, MD; Email: zonderj@karmanos.org
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine - Siteman Cancer Center
      • Contact: Mark Schroeder, MD; Email: markschroeder@wustl.edu
  • New York
    • New York, New York, United States, 10065
      • Not yet recruiting
      • New York-Presbyterian /Weill Cornell Medical Center - The Myeloma Center
      • Contact: Ruben Niesvizky, MD; Email: run9001@med.cornell.edu
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert Hospital & the Medical College of Wisconsin
      • Contact: Binod Dhakal, MD; Email: bdhakal@mcw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Dose escalation; Participants with R/R multiple myeloma (MM) will be administered ISB 1442 weekly by subcutaneous (SC) injection in each 28-day cycle. Dose escalation will begin with an accelerated titration dose escalation and should certain conversion criteria be met, escalation will convert to the standard (3 + 3) dose escalation	Drug: ISB 1442 SC injection escalating doses; Participants will receive escalating SC doses of ISB 1442
Experimental: Phase 2 (Dose Expansion): Cohort A: R/R Multiple Myeloma; This cohort includes the participants with pathologically confirmed R/R MM and must have received at least 3 prior lines of therapy, including proteasome inhibitors (PIs), immunomodulators (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. Participants will receive the recommended Phase 2 Dose (RP2D) of ISB 1442 SC injection determined in Phase 1 of the study for treatment of R/R MM. Each treatment cycle duration is 28 days. The anticipated total duration for each participant will vary, depending on the number of cycles of treatment completed. The treatment phase will extend until participants experience disease progression or unacceptable toxicity, or until any other discontinuation criterion is met.	Drug: ISB 1442 SC injection at RP2D; ISB 1442 SC injection dose regimen at RP2D until participants experience disease progression or unacceptable toxicity, or until any other discontinuation criterion is met
Experimental: Phase 2 (Dose Expansion): Cohort B: R/R MM Post-T-cell-Directed Therapy; This cohort includes the participants with pathologically confirmed R/R MM post T cell-directed therapy and have received prior treatment with proteasome inhibitors (PIs), immunomodulators (IMiDs), and anti-CD38 therapies either in combination or as a single agent; and must have failed at least 3 prior lines of treatment. Participants will receive the RP2D of ISB 1442 SC injection determined in Phase 1 of the study. Each treatment cycle duration is 28 days. The anticipated total duration for each participant will vary, depending on the number of cycles of treatment completed. The treatment phase will extend until participants experience disease progression or unacceptable toxicity, or until any other discontinuation criterion is met.	Drug: ISB 1442 SC injection at RP2D; ISB 1442 SC injection dose regimen at RP2D until participants experience disease progression or unacceptable toxicity, or until any other discontinuation criterion is met

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 1: Frequency and Severity Of Treatment-Emergent Adverse Events (TEAEs)	Up to 18 months
Phase 1: Number of Dose-Limiting Toxicities (DLTS) During the First 28 Days After the First Administration of ISB 1442 (Cycle 1)	Up to 28 days
Phase 2: Multiple Myeloma: Overall Response Rate (ORR) Based on International Myeloma Working Group (IMWG)	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Concentration (Cmax) of ISB 1442 in Serum	Up to 28 days
Time to Reach Maximum Concentration (Tmax) of ISB 1442 in Serum	Up to 28 days
Area Under the Concentration Time Curve From Zero to Time t (AUC0-t) of ISB 1442 in Serum	Up to 28 days
Area Under the Concentration Time Curve in Dosing Intervals (AUC0-tau) of ISB1442 in Serum	Up to 28 days
Percent Incidence of Anti-Drug Antibody (ADA) and Neutralizing Antibody (nAb) From Baseline Until End-of-Treatment (EOT)	Baseline to 18 months
Phase 1 and Phase 2: Time to Progression (TTP)	18 Months
Phase 1 and Phase 2: Time to Next Treatment (TTNT)	18 Months
Phase 1 and Phase 2: Time to Response (TTR)	18 Months
Phase 1 and Phase 2: Progression free survival (PFS)	18 Months
Phase 1 and Phase 2: Overall survival (OS)	18 Months
Phase 1: Overall Response Rate (ORR) Based on International Myeloma Working Group (IMWG)	18 months
Phase 1 and Phase 2: Complete Response Rate (CRR) Based on International Myeloma Working Group (IMWG)	18 months
Phase 1 and Phase 2: Duration of Response (DOR) Based on International Myeloma Working Group (IMWG)	18 months
Phase 2: Frequency and Severity of Treatment Emergent Adverse Events (TEAEs)	18 months

Collaborators and Investigators

• Sponsor: Ichnos Sciences SA

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2022
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: June 14, 2022
• First Submitted That Met QC Criteria: June 17, 2022
• First Posted (Actual): June 22, 2022

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Open-label; relapsed/refractory multiple myeloma; dose-escalation; dose-expansion; ISB 1442
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: ISB 1442-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No