Clinical trial NCT05427812: Phase 1/2 Study of ISB 1442 in Relapsed/Refractory Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Multiple Myeloma
Keywords: Open-label
dose-escalation
dose-expansion
ISB 1442
relapsed/refractory multiple myeloma
Lead sponsor: Ichnos Sciences SA
Sponsor class: INDUSTRY
First posted: 2022-06-22
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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, Phase 2 will be initiated for that indication. The Phase 2 design uses the Simon two-stage design with stopping rules for lack of activity, as well as stopping rules for toxicity. Participants will receive ISB 1442, until disease progression, unacceptable toxicity, or any criterion for stopping the study drug or withdrawal from the trial occurs.
Primary purpose: TREATMENT

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).

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

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.

Eligibility 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)
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.

Primary outcomes:
measure: Phase 1: Frequency and Severity Of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to 18 months
measure: Phase 1: Number of Dose-Limiting Toxicities (DLTS) During the First 28 Days After the First Administration of ISB 1442 (Cycle 1)
timeFrame: Up to 28 days
measure: Phase 2: Multiple Myeloma: Overall Response Rate (ORR) Based on International Myeloma Working Group (IMWG)
timeFrame: 18 months
Secondary outcomes:
measure: Maximum Concentration (Cmax) of ISB 1442 in Serum
timeFrame: Up to 28 days
measure: Time to Reach Maximum Concentration (Tmax) of ISB 1442 in Serum
timeFrame: Up to 28 days
measure: Area Under the Concentration Time Curve From Zero to Time t (AUC0-t) of ISB 1442 in Serum
timeFrame: Up to 28 days
measure: Area Under the Concentration Time Curve in Dosing Intervals (AUC0-tau) of ISB1442 in Serum
timeFrame: Up to 28 days
measure: Percent Incidence of Anti-Drug Antibody (ADA) and Neutralizing Antibody (nAb) From Baseline Until End-of-Treatment (EOT)
timeFrame: Baseline to 18 months
measure: Phase 1 and Phase 2: Time to Progression (TTP)
timeFrame: 18 Months
measure: Phase 1 and Phase 2: Time to Next Treatment (TTNT)
timeFrame: 18 Months
measure: Phase 1 and Phase 2: Time to Response (TTR)
timeFrame: 18 Months
measure: Phase 1 and Phase 2: Progression free survival (PFS)
timeFrame: 18 Months
measure: Phase 1 and Phase 2: Overall survival (OS)
timeFrame: 18 Months
measure: Phase 1: Overall Response Rate (ORR) Based on International Myeloma Working Group (IMWG)
timeFrame: 18 months
measure: Phase 1 and Phase 2: Complete Response Rate (CRR) Based on International Myeloma Working Group (IMWG)
timeFrame: 18 months
measure: Phase 1 and Phase 2: Duration of Response (DOR) Based on International Myeloma Working Group (IMWG)
timeFrame: 18 months
measure: Phase 2: Frequency and Severity of Treatment Emergent Adverse Events (TEAEs)
timeFrame: 18 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami - Sylvester Comprehensive Cancer Center
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Medical Center (UCMC) Duchossois Center for Advanced Medicine (DCAM)
state: Illinois
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main Campus
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: New York
country: United States
facility: New York-Presbyterian /Weill Cornell Medical Center - The Myeloma Center
state: New York
city: Milwaukee
country: United States
facility: Froedtert Hospital & The Medical College of Wisconsin
state: Wisconsin
city: Camperdown
country: Australia
facility: Royal Prince Albert Hospital: Institute of Haematology
state: New South Wales
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital-Melbourne
state: Victoria
city: Nedlands
country: Australia
facility: One Clinical Research Pty Ltd
state: Western Australia
city: Bangalore
country: India
facility: Health Care Global Enterprises Limited (HCG)
city: Bangalore
country: India
facility: M S Ramaiah Medical College & Hospital
city: Delhi
country: India
facility: Max Super Speciality Hospital
Study officials:
References: