Clinical trial NCT05862012: Study of ISB 2001 in Relapsed/Refractory Multiple Myeloma (TRIgnite-1)
Official title: A Phase 1, First-in-Human, Multicenter, Open-Label, Dose Escalation and Dose-Expansion Study of Single-Agent ISB 2001 in Subjects With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory Multiple Myeloma
Keywords: ISB 2001
Relapsed/refractory multiple myeloma
Open-label
Dose escalation
Dose expansion
Lead sponsor: Ichnos Sciences SA
Sponsor class: INDUSTRY
First posted: 2023-05-17
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is a first-in-human, Phase 1, open-label study that will evaluate safety and anti-myeloma activity of ISB 2001 in participants with relapsed/refractory multiple myeloma (R/R MM).

Detailed description: The study will enroll participants with R/R MM that have been treated with immunomodulatory drugs (IMiDs), proteasome inhibitors, and anti-CD38 therapies either in combination or as a single agent and are refractory to, or intolerant of, established therapies known to provide clinical benefit in MM.

The study will be conducted in two parts:

* Part 1: Dose escalation
* Part 2: Dose expansion

Dose escalation will continue until either the maximum tolerated dose (MTD) is defined, the maximum planned dose is reached, or a recommended phase 2 dose (RP2D) is selected. Dose expansion cohorts will be initiated to further confirm safety and optimal biologically active dose. Participants will receive ISB 2001 until disease progression, unacceptable toxicity occurs, any criterion for stopping the study treatment, or participant withdrawal from the study.

Eligibility criteria: Inclusion Criteria:

1. Participants with pathologically confirmed MM with measurable M-protein: serum and/or 24 hour urine, serum-free light chains or measurable isolated plasmacytoma
2. Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less
3. Must have adequate hematologic, hepatic, renal, and cardiac functions

Exclusion Criteria:

1. Active malignant central nervous system involvement
2. Uncontrolled infection requiring systemic antibiotic therapy or other serious infection prior to C1D1
3. History of autoimmune disease requiring systemic immunosuppressive therapy
4. Any concurrent or uncontrolled medical, comorbid, psychiatric or social condition that would limit compliance with study procedures, interfere with the study results, substantially increase the risk of AEs, compromise ability to provide written informed consent or, in the opinion of the Investigator, constitute a hazard for participating in this study.
5. Female subjects who are lactating and breastfeeding or have a positive pregnancy test during the screening period or on Day 1 before first dose of ISB 2001.

Primary outcomes:
measure: Frequency and Severity Of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to 18 months
measure: Number of Dose-Limiting Toxicities (DLT) During the First 28 Days After the First Administration of ISB 2001 (Cycle 1) in Each Cohort (Part 1)
timeFrame: Up to 28 days
Secondary outcomes:
measure: Maximum Concentration (Cmax) of ISB 2001 in Serum
timeFrame: Up to 28 days
measure: Time to Reach Maximum Concentration (Tmax) of ISB 2001 in Serum
timeFrame: Up to 28 days
measure: Area Under the Concentration Time Curve in Dosing Intervals (AUC0-tau) of ISB 2001 in Serum
timeFrame: Up to 28 days
measure: Area Under the Concentration Time Curve From Zero to Time t (AUC0-t) of ISB 2001 in Serum
timeFrame: Up to 28 days
measure: Percent Incidence of Anti-Drug Antibody (ADA), Neutralizing Antibody (nAb) and Titer of ADA From Baseline Until End-of-Treatment (EOT)
timeFrame: Baseline to 18 months
measure: Overall Response Rate (ORR) Based on International Myeloma Working Group (IMWG)
timeFrame: 18 months
measure: Complete Response Rate (CRR) Based on International Myeloma Working Group (IMWG)
timeFrame: 18 months
measure: Duration of Response (DOR) Based on International Myeloma Working Group (IMWG)
timeFrame: 18 months
measure: Time to Progression (TTP)
timeFrame: 18 months
measure: Time to Next Treatment (TTNT)
timeFrame: 18 months
measure: Time to Response (TTR)
timeFrame: 18 months
measure: Progression Free Survival (PFS)
timeFrame: 18 months
measure: Overall Survival (OS)
timeFrame: 18 months
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Standford Cancer Institute
state: California
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Concord
country: Australia
facility: Concord Hospital
state: New South Wales
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Bangalore
country: India
facility: HCG Hospital
Study officials:
References: