Health Condition 1: C900- Multiple myeloma
Conditions
Interventions
Intervention1: ISB 1442: Dosage Form: Lyophilized powder for solution for injection
Dose: Starting dose from 6 mg.
Dosage Frequency: Weekly, dosing on Days 1, 8, 15, and 22 of each 28-day
treatment cy
Sponsors
Ichnos Sciences SA
Glenmark Pharmaceuticals Ltd Glenmark House B D Sawant Marg
Eligibility
Inclusion 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 (e.g., 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): a) Must have received 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 benefits. b) Must have measurable M-protein (serum and/or 24-hour urine, or serum free light chains). 4. Phase 2a: Patients with pathologically confirmed MM who have progressed on or after standard therapy (R/R patients): Cohort A: R/R MM a) Must have measurable disease defined by at least 1 of the following abnormalities (as per IMWG criteria): • Serum M-protein = 0.5 g/dL (IgA = 0.5 g/dL), 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 a) Must have received 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 benefits. b) Must have measurable disease defined by at least 1 of the following abnormalities (as per IMWG criteria): • Serum M-protein = 0.5 g/dL (IgA = 0.5 g/dL), 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: a. Estimated creatinine clearance =45 mL/min as calculated using the Cockcroft-Gault formula or 24-hour urine analysis. b. Aspartate aminotransferase (AST, GOT) and alanine aminotransferase (ALT, GPT) =3.0 × ULN; bilirubin =1.5 × ULN. Patients with Gilberts syndrome may have a bilirubin level greater than 1.5 times ULN, per discussion between the Investigator and medical monitor. 9. Left ventricular ejection fraction (LVEF) =45% as assessed by echocardiogram (ECHO) or multiple gated acquisition (MUGA) scan.
Exclusion criteria
Exclusion criteria: 1. Patients 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. Note: Prophylactic localized (spot) radiation for areas of pain is allowed 3. Received treatment with anti-CD38 antibodies or CD47 targeted therapies within 28 days of C1D1; systemic anticancer treatments within 14 days of (C1D1) or any investigational products within 5 half-lives of 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/day 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. Active malignant central nervous system involvement 7. Known to be refractory to platelet or RBC transfusions 8. Known severe allergic or anaphylactic reactions to human recombinant proteins or excipients used in the ISB 1442 formulation. 9. Prior radiation therapy within 14 days of C1D1 or prior irradiation to greater than 25% of the bone marrow. Note: Prophylactic localized (spot) radiation for areas of pain is allowed. 10. QTc interval greater than 480 msec at screening using Fredericias QT correction formula.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Phase 1: Frequency and Severity of Treatment-Emergent Adverse Events (TEAEs) 2. Phase 1: For MTD: Number of Dose-Limiting Toxicities (DLTS) During the First 28 Days After the First Administration of ISB 1442 (Cycle 1) in each cohort 3. Phase 2a: Overall Response Rate (ORR) Based on investigators assessment according to International Myeloma Working Group (IMWG)Timepoint: 1. Up to 18 months 2. Up to 28 days 3. 18 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Maximum Concentration (Cmax) of ISB 1442 in SerumTimepoint: Up to 28 days;2. Time to Reach Maximum Concentration (Tmax) of ISB 1442 in SerumTimepoint: Up to 28 days;3. Area Under the Concentration Time Curve From Zero to Time t (AUC0-t) of ISB 1442 in SerumTimepoint: Up to 28 days;4. Area Under the Concentration Time Curve in Dosing Intervals (AUC0-tau) of ISB1442 in SerumTimepoint: Up to 28 days;5. Percent Incidence of Anti-Drug Antibody (ADA) and Neutralizing Antibody (nAb) From Baseline Until End-of-Treatment (EOT)Timepoint: Baseline to 18 months;Phase 1 and Phase 2a: Time to Progression (TTP)Timepoint: 18 Months;7. Phase 1 and Phase 2a: Time to Next Treatment (TTNT)Timepoint: 18 Months;8. Phase 1 and Phase 2a: Time to Response (TTR)Timepoint: 18 Months;9. Phase 1 and Phase 2a: Progression free survival (PFS)Timepoint: 18 Months;10. Phase 1 and Phase 2a: Overall survival (OS)Timepoint: 18 Months;11. Phase 1: Overall Response Rate (ORR) Based on International Myeloma Working Group (IMWG)Timepoint: 18 months;12. Phase 1 and Phase 2a: Complete Response Rate (CRR) Based on International Myeloma Working Group (IMWG)Timepoint: 18 months;13. Phase 1 and Phase 2a: Duration of Response (DOR) Based on International Myeloma Working Group (IMWG)Timepoint: 18 months;14. Phase 2a: Frequency and Severity of Treatment Emergent Adverse Events (TEAEs)Timepoint: 18 months | — |
Countries
Australia, India, United States of America
Contacts
Public ContactJatin Kadam
Glenmark Pharmaceuticals LTD.
Outcome results
None listed