A Phase 1, Open-Label, Dose-Escalation Study to Determine an Appropriate Starting Dose of Sacituzumab Govitecan in Subjects With Advanced or Metastatic Solid Tumor and Moderate Liver Impairment
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 15
- 主要终点
- Percentage of Participants experiencing Treatment Emergent Adverse Events (TEAEs) and Serious AEs
研究概览
简要总结
The goals of this clinical study are to learn more about the safety and dosing of the study drug, sacituzumab govitecan-hziy, in participants with solid tumors and moderate liver problems.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for all Individuals:
- •Histologically confirmed advanced or metastatic solid tumor that is measurable or nonmeasurable.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or
- •Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥1,500/mm^3, and platelets ≥ 100,000/ μL).
- •Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation.
- •Key Inclusion Criteria for Individuals with Normal Hepatic Function:
- •Normal hepatic function (total bilirubin ≤ ULN and aspartate aminotransferase (AST) ≤ 3.0× ULN).
- •Key Inclusion Criteria for Individuals with Moderate Hepatic Function:
- •Moderate hepatic impairment (1.5 × ULN < total bilirubin ≤ 3.0 × ULN and any level of AST).
- •For individuals with hepatic encephalopathy, the condition does not, in the Investigator's opinion, interfere with the individual's ability to provide an appropriate informed consent.
排除标准
- •for all Individuals:
- •Have poor venous access.
- •Donated or lost 500mL or more of blood volume (including plasmapheresis) to plans to donate during the study.
- •Have had a prior anticancer biologic agent within 4 weeks prior to Day 1 or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Day 1 and who have not recovered (i.e., ≤ Grade 1) from adverse events (AEs) at the time of study entry. Individuals participating in observational studies are eligible.
- •Had prior treatment with irinotecan within 4 weeks prior to Day
- •Have not recovered (i.e., ≤ Grade 1) from AEs due to a previously administered agent.
- •Have an active second malignancy.
- •Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Individuals with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are taking < 20 mg/day of prednisone or its equivalent. All individuals with carcinomatous meningitis are excluded regardless of clinical stability.
- •Have history of cardiac disease.
- •Have active chronic inflammatory bowel disease (ulcerative colitis or Crohn's disease) or gastrointestinal (GI) perforation within 6 months of enrollment.
- •Have active serious infection (Contact medical monitor for clarification).
- •High-dose systemic corticosteroids (≥20 mg of prednisone or its equivalent) are not allowed within 2 weeks of Check-In. However, inhaled, intranasal, intra-articular, and topical steroids are allowed.
- •Use of strong inhibitor or inducer of UGT1A
- •Have a known history of Gilbert's disease.
- •Key Exclusion Criteria for Individuals with Normal Hepatic Impairment:
- •Must have pre-existing condition interfering with hepatic and/or renal function that could interfere with the metabolism and/or excretion of the study drug.
- •Key Exclusion Criteria for Individuals with Moderate Hepatic Impairment:
- •Had a significant clinical exacerbation of liver disease symptoms within the 2-week period before administration of study drug (i.e., abdominal pain, nausea, vomiting, anorexia, or fever).
- •Had clinically demonstrable, tense ascites.
- •Had evidence of acute viral hepatitis within 1 month prior to administration of study drug.
- •Have evidence of hepatorenal syndrome.
- •Individuals with transjugular intrahepatic portosystemic shunt (TIPS) placement.
- •Have active Stage 3 or 4 encephalopathy.
研究组 & 干预措施
Advanced or Metastatic Solid Tumor and Moderate Liver Impairment
Participants with advanced solid tumor and moderate hepatic impairment will receive an escalating dose of sacituzumab govitecan-hziy on Days 1 and 8. The dose-escalation plan will start at 5 mg/kg and escalate to 7.5 mg/kg, and finally 10 mg/kg, if deemed to be safe. At the completion of study treatment, participants who are deriving benefit from sacituzumab govitecan-hziy may continue to receive treatment in a Gilead sponsored rollover study (IMMU-132-14; NCT04319198).
干预措施: Sacituzumab Govitecan-hziy (Drug)
Advanced or Metastatic Solid Tumor and Normal Liver function
Participants with advanced or metastatic solid tumor and normal hepatic function will receive sacituzumab govitecan-hziy 10 mg/kg on Days 1 and 8. At the completion of study treatment, participants who are deriving benefit from sacituzumab govitecan-hziy may continue to receive treatment in a Gilead sponsored rollover study (IMMU-132-14; NCT04319198).
干预措施: Sacituzumab Govitecan-hziy (Drug)
结局指标
主要结局
Percentage of Participants experiencing Treatment Emergent Adverse Events (TEAEs) and Serious AEs
时间窗: First dose date up to Day 38
Percentage of Participants Experiencing Any Dose Limiting Toxicities (DLTs)
时间窗: Up to Day 22 (for participants receiving SG on Day 1); Up to Day 28 (for participants receiving SG on Day 8)
Percentage of Participants Experiencing Any Clinically Significant Laboratory Abnormalities
时间窗: First dose date up to Day 38
Pharmacokinetic (PK) Parameter: Cmax of Free SN-38 and Sacituzumab Govitecan-hziy
时间窗: Days 1 and 8
Cmax will be determined for 2 analytes: Free SN-38 and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. Cmax is defined as the maximum observed concentration obtained directly from the observed concentration-time data.
PK Parameter: AUC 0-168 of Free SN-38 and Sacituzumab Govitecan-hziy
时间窗: Days 1 and 8
AUC 0-168 will be determined for 2 analytes: Free SN-38 and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-168 is defined as area under the serum concentration-time curve from time 0 to 168 hours.
Percentage of Participants who Develop Anti-Sacituzumab Govitecan-hziy Antibodies
时间窗: Day 1 (Predose) and Day 22
次要结局
未报告次要终点