CTRI/2024/04/065308Other (Terminated)1/2 期
A Phase 1/2, First-in-Human, Multicentre, Open-Label, Dose Escalation and Dose-Expansion Study of Single-Agent ISB 1442 in Patients with Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1/2 期
- 状态
- Other (Terminated)
- 入组人数
- 121
- 试验地点
- 9
- 主要终点
- 1. Phase 1: Frequency and Severity of Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a first-in-human, Phase 1/2a, open label study evaluating safety and efficacy of ISB 1442 in patients with relapsed/ refractory (R/R) multiple myeloma (MM).
Patients 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or female patients aged 18 years or older.
- •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
- •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).
- •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
- •Have a body weight ≥ 40.0 kg at screening.
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less.
- •Have life expectancy of at least 3 months (from date of informed consent signing).
- •Estimated creatinine clearance ≥45 mL/min as calculated using the Cockcroft-Gault formula or 24-hour urine analysis.
- •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.
- •Left ventricular ejection fraction (LVEF) ≥45% as assessed by echocardiogram (ECHO) or multiple gated acquisition (MUGA) scan.
排除标准
- •Patients with relapsed disease where relapse is characterized only by minimal residual disease parameters (i.e., minimal residual disease positive).
- •Participants with MM with disease where the only measurable parameter is plasmacytoma.
- •Note: Prophylactic localized ("spot") radiation for areas of pain is allowed
- •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 C1D
- •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-Î’ ligand inhibitors are allowed.
- •Received autologous stem cell transplantation within 12 weeks of C1D
- •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.
- •Active malignant central nervous system involvement
- •Known to be refractory to platelet or RBC transfusions
- •Known severe allergic or anaphylactic reactions to human recombinant proteins or excipients used in the ISB 1442 formulation.
- •Prior radiation therapy within 14 days of C1D1 or prior irradiation to greater than 25% of the bone marrow.
- •QTc interval greater than 480 msec at screening using Fredericias QT correction formula.
结局指标
主要结局
1. Phase 1: Frequency and Severity of Treatment-Emergent Adverse Events (TEAEs)
时间窗: 1. Up to 18 months | 2. Up to 28 days | 3. 18 months
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
时间窗: 1. Up to 18 months | 2. Up to 28 days | 3. 18 months
3. Phase 2a: Overall Response Rate (ORR) Based on investigators assessment according to International Myeloma Working Group (IMWG)
时间窗: 1. Up to 18 months | 2. Up to 28 days | 3. 18 months
次要结局
- 1. Maximum Concentration (Cmax) of ISB 1442 in Serum(Up to 28 days)
- 2. Time to Reach Maximum Concentration (Tmax) of ISB 1442 in Serum(Up to 28 days)
- 3. Area Under the Concentration Time Curve From Zero to Time t (AUC0-t) of ISB 1442 in Serum(Up to 28 days)
- 4. Area Under the Concentration Time Curve in Dosing Intervals (AUC0-tau) of ISB1442 in Serum(Up to 28 days)
- 5. Percent Incidence of Anti-Drug Antibody (ADA) and Neutralizing Antibody (nAb) From Baseline Until End-of-Treatment (EOT)(Baseline to 18 months)
- Phase 1 and Phase 2a: Time to Progression (TTP)(18 Months)
- 7. Phase 1 and Phase 2a: Time to Next Treatment (TTNT)(18 Months)
- 8. Phase 1 and Phase 2a: Time to Response (TTR)(18 Months)
- 9. Phase 1 and Phase 2a: Progression free survival (PFS)(18 Months)
- 10. Phase 1 and Phase 2a: Overall survival (OS)(18 Months)
- 11. Phase 1: Overall Response Rate (ORR) Based on International Myeloma Working Group (IMWG)(18 months)
- 12. Phase 1 and Phase 2a: Complete Response Rate (CRR) Based on International Myeloma Working Group (IMWG)(18 months)
- 13. Phase 1 and Phase 2a: Duration of Response (DOR) Based on International Myeloma Working Group (IMWG)(18 months)
- 14. Phase 2a: Frequency and Severity of Treatment Emergent Adverse Events (TEAEs)(18 months)
研究者
Dr. Veena Gupta
Glenmark Pharmaceuticals LTD.
研究点 (9)
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