Not Yet RecruitingPhase 2ACTRN12622000856718

A First-in-Human Study of Single-Agent ISB 1442 in Patients with Relapsed/Refractory Multiple Myeloma

A Phase 1/2, First-in-Human, Multicenter, Open-Label, Dose Escalation and Dose-Expansion Study assessing safety and tolerability of Single-Agent ISB 1442 in Patients with Relapsed/Refractory Multiple Myeloma

Sponsor

Ichnos Sciences SA

Enrollment

121 participants

Start Date

Jul 25, 2022

Study Type

Interventional

Conditions

Refractory Multiple Myeloma Relapsed Multiple Myeloma

Summary

This study is a first-in-human trial that will evaluate the safety and efficacy of ISB 1442, a novel immune therapy for the treatment of relapsed/ refractory (R/R) multiple myeloma (MM). Who is it for? You may be eligible for this study if you are an adult aged 18 or older, you have been diagnosed with multiple myeloma who have progressed on or after standard therapy. Participants will also need to meet set criteria regarding their overall health to be eligible to participate in this study, e.g. meet study requirements for their kidney, liver and heart function prior to enrolling. Study details This study will be conducted in two parts. Participants who choose to enrol in Phase 1 will not be eligible to enrol again in Phase 2. Phase 1: Patients will be treated with escalating dose levels of ISB 1442, administered by a study nurse as a subcutaneous (under the skin) injection on Days 1, 8, 15 and 22 of a 28-day cycle. A separate group of participants will be enrolled for each dose level, however the study will not progress to a higher dose if any unacceptable adverse events/side effects are seen in the previous dose group. Dose escalation decisions will be made by the safety monitoring committee (SMC). The SMC will review safety and exposure data for all patients enrolled in a given cohort. Phase 2: Once the maximum tolerated dose of ISB 1442 has been found in Phase 1, new groups of participants will be enrolled into Phase 2 to examine the effects of ISB 1442 over a longer period of time. Participants who choose to enrol in Phase 2 will also receive ISB 1442, administered by a study nurse as a subcutaneous (under the skin) injection on Days 1, 8, 15 and 22 of a 28-day cycle. Participants will receive ISB 1442 until disease progression, unacceptable toxicity, or any criterion for stopping the study drug or withdrawal from the trial occurs. The expected duration for each Phase of this study is approximately 48 months: approximately 30 months for enrollment and approximately 18 months for treatment and/or follow-up. It is hoped this study will determine the safe dose of ISB 1442 that is effective against relapsed/ refractory multiple myeloma. ISB 1442 may then be used as an effective treatment for future patients who have multiple myeloma.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria9

Male or female patients aged 18 years or older.
Willing and able to provide written informed consent.
Patients with pathologically confirmed and measurable multiple myeloma (MM) who have progressed on or after standard therapy.
Patients must have received: a proteosome inhibitor (PI), a immune modulator (IMiD), and an anti-CD38 therapies either in combination or as a single agent; and must not be candidates for regimens known to provide clinical benefit.
Body weight more than 40.0 kg.
Patients must have adequate hematologic and organ function laboratory values.
Left ventricular ejection fraction (LVEF) more than 45% as assessed by echocardiogram (ECHO) or multiple gated acquisition (MUGA) scan.
Have a negative serum pregnancy test result at screening for women of childbearing potential.
Must agree to acceptable contraception.

Exclusion Criteria7

Cannot have diagnosis of primary amyloidosis, Waldenström’s disease, smoldering multiple myeloma, POEMS syndrome, myelodysplastic syndrome, or myeloproliferative syndrome.
Cannot have prior treatment or radiation within 14 days before first dose of study drug.
Cannot have autologous stem cell transplantation within 12 weeks of first dose of study drug.
Cannot have other investigation agent, live vaccine, or major surgery within 4 weeks of first dose of study drug.
Cannot have known history of human immunodeficiency virus (HIV) infection or any other relevant congenital or acquired immunodeficiency.
Cannot have history of allogeneic tissue or solid organ transplant.
Cannot have history of any of congestive heart failure, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled hypertension despite appropriate medical therapy, symptomatic cardiac arrhythmias, pulmonary embolism or any other serious cardiac condition within 6 months of first dose of study drug.

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Interventions

ISB 1442 is a potential first-in-class CD38 x CD47 bispecific, biparatopic antibody generated using Ichnos’ BEAT® 2.0 technology. ISB 1442 is designed to kill CD38-expressing tumor cells The Study consists of two parts Phase 1 (Dose Escalation phase) Investigational Product (IP): ISB 1442 Dosage Form: Lyophilized powder Mode of Administration: Subcutaneous (SC) Injection Dosage frequency: For all cohorts, dosing will occur once on Days 1, 8, 15, and 22 of each 28-day cycle, for a maximum of typically approximately 4 cycles. However, the maximum number of cycles could be endless, as participants may continue on the assigned dose within their cohort until disease progression, intolerability or withdrawal of consent. Cohort 1: 6 mg of ISB 1442 administered once on Days 1, 8, 15 and 22 of each 28-day cycle Cohort 2: 20 mg of ISB 1442 administered once on Days 1, 8, 15 and 22 of each 28-day cycle Cohort 3: 60 mg of ISB 1442 administered once on Days 1, 8, 15 and 22 of each28-day cycle Cohort 4: 150 mg of ISB 1442 administered once on Days 1, 8, 15 and 22 of each 28-day cycle Cohort 5: 300 mg of ISB 1442 administered once on Days 1, 8, 15 and 22 of each 28-day cycle Cohort 6: 600 mg of ISB 1442 administered once on Days 1, 8, 15 and 22 of each 28-day cycle Cohort 7: 1200 mg of ISB 1442 administered once on Days 1, 8, 15, 22 of each 28-day cycle Dose escalation will continue until either Maximum Tolerated Dose (MTD) is defined, the maximum planned dose is reached, or a recommended Phase 2 dose (RP2D) is selected. Decisions with regards to step-up/priming dose levels and schedule will be made by the Safety Monitoring Committee (SMC) To allow for assessment of safety, the dosing of all patients within each dose level cohort should be staggered with at least 24 hours between each patient. Agreement from the SMC must be obtained before treatment of the next dose escalation cohort can start. The IP will be administered subcutaneously by authorized site staff once weekly on Days 1, 8, 15, 22 in a 28-day cycle for all cohorts. Phase 2 (Dose Expansion Phase) Investigational Product: ISB 1442 Dosage Form: Lyophilized powder Mode of Administration: Subcutaneous (SC) Injection About 4-8 weeks after the recommended Phase 2 dose (RP2D) of ISB 1442 is established in Phase 1, Phase 2 expansions will be initiated to further evaluate safety and efficacy of ISB 1422. The phase 2 of study will enroll two distinct cohorts (Cohort A: Relapsed/Refractory (R/R) Multiple Myeloma (MM) and Cohort B: R/R MM Post-T-Cell-Directed Therapy) of participants. The participants in each cohort will receive ISB 1442 on day 1, 8, 15 and 22 of each 28-day cycles, for a maximum of typically approximately 12 cycles, however, the maximum number of cycles could be endless, as participants may continue on the assigned Phase 2 dose until disease progression, intolerability or withdrawal of consent. The IP will be administered subcutaneously by authorized site staff once weekly on Days 1, 8, 15, 22 in a 28-day cycle. The phase 1 and phase 2 of the study will enroll distinct group of participants.