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

Relapsed/Refractory Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05427812
• Other study ID #: ISB 1442-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 27, 2022
• Est. completion date: May 1, 2027

Study information

• Verified date: May 2023
• Source: Ichnos Sciences SA
• Contact: Ichnos Sciences Clinical Trials Administrator
• Phone: (315) 583-1249
• Email: clinicaltrials[@]ichnossciences.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 121
• Est. completion date: May 1, 2027
• Est. primary completion date: May 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-? 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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/Refractory Multiple Myeloma

Intervention

Drug:
• ISB 1442 SC injection escalating doses
Participants will receive escalating SC doses of ISB 1442
• 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

Locations

Country	Name	City	State
Australia	Pindara Private Hospital	Benowa	Queensland
Australia	Royal Prince Albert Hospital: Institute of Haematology	Camperdown	New South Wales
Australia	St. Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	The Alfred Hospital-Melbourne	Melbourne	Victoria
Australia	One Clinical Research Pty Ltd	Nedlands	Western Australia
Australia	Gold Coast University Hospital	Southport	Queensland
United States	The University of Chicago Medical Center (UCMC) Duchossois Center for Advanced Medicine (DCAM)	Chicago	Illinois
United States	Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main Campus	Detroit	Michigan
United States	University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Froedtert Hospital & The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	New York-Presbyterian /Weill Cornell Medical Center - The Myeloma Center	New York	New York
United States	Washington University School of Medicine - Siteman Cancer Center	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Ichnos Sciences SA

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

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