NCT07297979招募中1 期
A Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Xaluritamig in Adult, Adolescent and Pediatric Participants With Relapsed or Refractory Ewing Sarcoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Amgen
- 入组人数
- 50
- 试验地点
- 9
- 主要终点
- Number of Participants Experiencing a Dose-limiting Toxicity (DLT) (Part 1 Only)
研究概览
简要总结
The main objectives of this trial are to determine the recommended dose for expansion of xaluritamig (dose confirmation part only) and to determine the safety and tolerability of xaluritamig in adult, adolescent and pediatric participants with relapsed or refractory EWS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part 1: evaluable disease as defined by RECIST v1.1, as determined by the site investigator.
- •Part 2: measurable disease as defined by RECIST v1.1, as determined by the site investigator.
- •Histologically or cytologically confirmed EWS with molecular evidence of an EWSR1 translocation with an E26 transformation-specific (ETS) family gene, eg, FLI1, ETS-related gene [ERG]) via next generation sequencing (based on local testing).
- •Relapsed or refractory EWS following at least 1 line of chemotherapy (including treatment with an anthracycline and at least 1 alkylating agent).
- •Performance status:
- •Karnofsky ≥ 70% for participants ≥ 16 years of age.
- •Lansky ≥ 70% for participants < 16 years of age.
- •Adequate organ function, defined as follows:
- •a. Hematological function: i. Absolute neutrophil count ≥ 1.0 x 109/L, provided that:
- •the participant has not received short-acting growth factor support within 7 days before screening assessment, and
- •the participant has not received long-acting growth factor support within 14 days before screening assessment.
- •ii. Platelet count ≥ 75 x 109/L, provided that:
- •the participant has not received a platelet transfusion within 7 days before screening assessment, and
- •the participant has not received a platelet stimulating agent within 14 days before screening assessment.
- •b. Renal function: i. Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation ≥ 30 mL/min/1.73 m^2 for participants ≥ 18 years of age.
- •ii. estimated glomerular filtration rate based on Schwartz (2009) calculation ≥ 30 mL/min/1.73 m^2 for participants < 18 years of age.
- •c. Hepatic function: i. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) (or ≤ 5 x ULN for participants with liver metastases).
- •ii. Total bilirubin (TBL) ≤ 1.5 x ULN (unless related to Gilbert's or Meulengracht disease).
- •d. Pulmonary function: i. Baseline oxygen saturation > 92% in room air at rest and no oxygen supplementation.
- •e. Cardiac function: i. Left ventricular ejection fraction ≥ 50%. If left ventricular ejection fraction cannot be measured, then left ventricular fractional shortening ≥ 28%.
- •Participants of childbearing potential must use protocol-specified contraception to prevent pregnancy during treatment and for an additional 6 months after the last dose of xaluritamig.
排除标准
- •Untreated central nervous system (CNS) metastases or leptomeningeal disease. Participants with a history of treated CNS metastases are eligible if there is radiographic evidence of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study.
- •History of other malignancy within the past 2 years, except for malignancy treated with curative intent with low risk for recurrence (approximately < 10%) and with no known active disease present for >1 year before enrollment.
- •Active autoimmune disease that has required systemic treatment (except physiologic adrenal hormone replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study. Participants with Type 1 diabetes, vitiligo, psoriasis, hypo- or hyper-thyroid disease not requiring immunosuppressive treatment are permitted.
- •Participants who received anti-cancer therapy administered within the following minimum washout periods prior to first dose of xaluritamig:
- •Cytotoxic chemotherapy: 21 days.
- •Small molecules including tyrosine kinase inhibitors: 7 days or 5 half-lives, whichever is shorter.
- •Monoclonal antibodies, immune checkpoint inhibitors, bispecific antibodies and other biologic agents: 28 days or 5 half-lives, whichever is shorter.
- •Cellular therapies including Chimeric Antigen Receptor T-cell therapy (CAR-T), adoptive T-cell therapy: 56 days.
- •Radiotherapy: 14 days for focal therapy, 28 days for large field therapy or involving > 30% of the bone marrow.
- •Stem cell transplant: 12 weeks for autologous, 6 months for allogeneic, with no active graft-versus-host disease.
- •Any other therapy or investigational agent: 28 days or 5 half-lives, whichever is longer.
- •Requirement for chronic systemic corticosteroid therapy (prednisone dose > 10 mg/day [> 0.25 mg/kg/day if < 40 kg] or equivalent) or any other immunosuppressive therapies (including anti-tumour necrosis factor α (TNFα) therapies) unless stopped (with adequate tapering) within 28 days before first dose of xaluritamig.
- •Currently pregnant (confirmed with positive pregnancy test) or breastfeeding or planning to become pregnant, donate eggs, or breastfeed while on trial until an additional 6 months after the last dose of trial intervention.
- •Unwilling to abstain from donating sperm during treatment and for an additional 6 months after the last dose of xaluritamig.
研究组 & 干预措施
Part 1 (Dose Confirmation)
Experimental
Part 1 will begin with a pre-specified xaluritamig target dose and frequency. Multiple dose levels and/or alternative dose regimens may be explored in parallel to determine 1 or more recommended doses for expansion, which is/are considered safe, based on emerging data.
干预措施: Xaluritamig (Drug)
Part 2 (Dose Expansion)
Experimental
Participants will be treated in Part 2 after the recommended doses for expansion for xaluritamig are determined in Part 1 to further characterize preliminary antitumor activity and safety.
干预措施: Xaluritamig (Drug)
结局指标
主要结局
Number of Participants Experiencing a Dose-limiting Toxicity (DLT) (Part 1 Only)
时间窗: Up to 42 days
Number of Participants with Treatment-emergent Adverse Events
时间窗: Up to approximately 2.5 years
This includes treatment-emergent, treatment-related, serious, and fatal adverse events. Any changes in safety assessments (vital signs and clinical laboratory tests) will be recorded as adverse events.
次要结局
- Maximum Serum Concentration (Cmax) of Xaluritamig(Up to approximately 6 months)
- Time to Cmax (tmax) of Xaluritamig(Up to approximately 6 months)
- Minimum Serum Concentration (Cmin) of Xaluritamig(Up to approximately 6 months)
- Accumulation Following Multiple Doses of Xaluritamig(Up to approximately 6 months)
- Serum Concentration Before Dosing (Ctrough) of Xaluritamig(Up to approximately 6 months)
- Half-life (t½) of Xaluritamig(Up to approximately 6 months)
- Area Under the Serum Concentration-time Curve (AUC) of Xaluritamig(Up to approximately 6 months)
- Confirmed Objective Response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1(Up to approximately 6 months)
- Disease Control per RECIST v1.1(Up to approximately 6 months)
- Time to Response (TTR) per RECIST v1.1(Up to approximately 6 months)
- Duration of Confirmed Response (DOR) per RECIST v1.1(Up to approximately 6 months)
- Progression-free Survival (PFS) per RECIST v1.1(Up to approximately 6 months)
- Time to Progression (TTP) per RECIST v1.1(Up to approximately 6 months)
- Time to First Subsequent Anti-cancer Therapy(Up to approximately 6 months)
- Overall Survival (OS)(Up to approximately 2 years)
- Number of Participants with Anti-xaluritamig Antibody Formation(Up to approximately 6 months)
研究者
研究点 (9)
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