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

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05427812
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Ichnos Sciences SA
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Australia, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Relapsed/Refractory Multiple Myeloma
Additional Details

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.

Arms & Interventions

Arms

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

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.

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.

Interventions

Drug: - ISB 1442 SC injection escalating doses

Participants will receive escalating SC doses of ISB 1442

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Mount Sinai, New York, New York

Status

Not yet recruiting

Address

Mount Sinai

New York, New York, 10025

Site Contact

Joshua Richter, MD

joshua.richter@mountsinai.org

(315) 583-1249

International Sites

Camperdown, New South Wales, Australia

Status

Not yet recruiting

Address

Royal Prince Albert Hospital: Institute of Haematology

Camperdown, New South Wales, 2050

Site Contact

Jo Ho, MBBS,D.Phil,FRACP,FRCPA,FFSc

joy.ho1@health.nsw.gov.au

(315) 583-1249

Pindara Private Hospital, Benowa, Queensland, Australia

Status

Recruiting

Address

Pindara Private Hospital

Benowa, Queensland, 4217

Site Contact

Hanlon Sia, MBBS(Adelaide), FRACP, FRCPA

hanlonsia@yahoo.com.au

(315) 583-1249

Gold Coast University Hospital, Southport, Queensland, Australia

Status

Not yet recruiting

Address

Gold Coast University Hospital

Southport, Queensland, 4211

Site Contact

Tara Cochrane, MD

tara.cochrane@health.qld.gov.au

(315) 583-1249

The Alfred Hospital-Melbourne, Melbourne, Victoria, Australia

Status

Not yet recruiting

Address

The Alfred Hospital-Melbourne

Melbourne, Victoria, 3004

Site Contact

Andrew Spencer, MBBS FRACP FRCPA DM

andrew.spencer@monash.edu

(315) 583-1249

One Clinical Research Pty Ltd, Nedlands, Western Australia, Australia

Status

Recruiting

Address

One Clinical Research Pty Ltd

Nedlands, Western Australia, 6009

Site Contact

Peter Tan, MBBS(Hons),MPhil,FRACP,FRCPA

peter.tan@oneclinicalresearch.com.au

(315) 583-1249