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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05427812




Registration number
NCT05427812
Ethics application status
Date submitted
14/06/2022
Date registered
22/06/2022
Date last updated
1/06/2023

Titles & IDs
Public title
Phase 1/2 Study of ISB 1442 in Relapsed/Refractory Multiple Myeloma
Scientific 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
Secondary ID [1] 0 0
ISB 1442-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ISB 1442 SC injection escalating doses
Treatment: Drugs - ISB 1442 SC injection at RP2D

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.


Treatment: Drugs: ISB 1442 SC injection escalating doses
Participants will receive escalating SC doses of ISB 1442

Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Frequency and Severity Of Treatment-Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Up to 18 months
Primary outcome [2] 0 0
Phase 1: Number of Dose-Limiting Toxicities (DLTS) During the First 28 Days After the First Administration of ISB 1442 (Cycle 1)
Timepoint [2] 0 0
Up to 28 days
Primary outcome [3] 0 0
Phase 2: Multiple Myeloma: Overall Response Rate (ORR) Based on International Myeloma Working Group (IMWG)
Timepoint [3] 0 0
18 months
Secondary outcome [1] 0 0
Maximum Concentration (Cmax) of ISB 1442 in Serum
Timepoint [1] 0 0
Up to 28 days
Secondary outcome [2] 0 0
Time to Reach Maximum Concentration (Tmax) of ISB 1442 in Serum
Timepoint [2] 0 0
Up to 28 days
Secondary outcome [3] 0 0
Area Under the Concentration Time Curve From Zero to Time t (AUC0-t) of ISB 1442 in Serum
Timepoint [3] 0 0
Up to 28 days
Secondary outcome [4] 0 0
Area Under the Concentration Time Curve in Dosing Intervals (AUC0-tau) of ISB1442 in Serum
Timepoint [4] 0 0
Up to 28 days
Secondary outcome [5] 0 0
Percent Incidence of Anti-Drug Antibody (ADA) and Neutralizing Antibody (nAb) From Baseline Until End-of-Treatment (EOT)
Timepoint [5] 0 0
Baseline to 18 months
Secondary outcome [6] 0 0
Phase 1 and Phase 2: Time to Progression (TTP)
Timepoint [6] 0 0
18 Months
Secondary outcome [7] 0 0
Phase 1 and Phase 2: Time to Next Treatment (TTNT)
Timepoint [7] 0 0
18 Months
Secondary outcome [8] 0 0
Phase 1 and Phase 2: Time to Response (TTR)
Timepoint [8] 0 0
18 Months
Secondary outcome [9] 0 0
Phase 1 and Phase 2: Progression free survival (PFS)
Timepoint [9] 0 0
18 Months
Secondary outcome [10] 0 0
Phase 1 and Phase 2: Overall survival (OS)
Timepoint [10] 0 0
18 Months
Secondary outcome [11] 0 0
Phase 1: Overall Response Rate (ORR) Based on International Myeloma Working Group (IMWG)
Timepoint [11] 0 0
18 months
Secondary outcome [12] 0 0
Phase 1 and Phase 2: Complete Response Rate (CRR) Based on International Myeloma Working Group (IMWG)
Timepoint [12] 0 0
18 months
Secondary outcome [13] 0 0
Phase 1 and Phase 2: Duration of Response (DOR) Based on International Myeloma Working Group (IMWG)
Timepoint [13] 0 0
18 months
Secondary outcome [14] 0 0
Phase 2: Frequency and Severity of Treatment Emergent Adverse Events (TEAEs)
Timepoint [14] 0 0
18 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/09/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2027
Actual
Sample size
Target
121
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Albert Hospital: Institute of Haematology - Camperdown
Recruitment hospital [2] 0 0
Pindara Private Hospital - Benowa
Recruitment hospital [3] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [4] 0 0
St. Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [5] 0 0
The Alfred Hospital-Melbourne - Melbourne
Recruitment hospital [6] 0 0
One Clinical Research Pty Ltd - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4217 - Benowa
Recruitment postcode(s) [3] 0 0
4211 - Southport
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Wisconsin

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Ichnos Sciences SA
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05427812
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ichnos Sciences Clinical Trials Administrator
Address 0 0
Country 0 0
Phone 0 0
(315) 583-1249
Fax 0 0
Email 0 0
clinicaltrials@ichnossciences.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05427812