Study of Sacituzumab Govitecan in Participants With Advanced or Metastatic Solid Tumor and Moderate Liver Impairment

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced or Metastatic Solid Tumor, Liver Failure

Intervention / Treatment
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* Drug: Sacituzumab Govitecan-hziy


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria 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 2. 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. Key Exclusion Criteria 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 2) 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 1 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 requiring intravenous antibiotics (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 UGT1A1 Have a 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 clinical exacerbation of liver disease 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Advanced or Metastatic Solid Tumor and Moderate Liver Impairment<br>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). | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously<br>* Other names: GS-0132;|
| Experimental: Advanced or Metastatic Solid Tumor and Normal Liver function<br>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). | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously<br>* Other names: GS-0132;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants experiencing Treatment Emergent Adverse Events (TEAEs) |  | First dose date up to Day 38 | 
| Percentage of Participants Experiencing Any Clinically Significant Laboratory Abnormalities |  | First dose date up to Day 38 | 
| PK Parameter: Cmax of Free SN-38, SN-38 Glucuronide, Total SN-38, and Sacituzumab Govitecan-hziy | Cmax will be determined for 4 analytes: Free SN-38, SN-38 glucuronide, Total 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. | Days 1 and 8 | 
| PK Parameter: AUC_last of Free SN-38, SN-38 Glucuronide, Total SN-38, and Sacituzumab Govitecan-hziy | AUC_last will be determined for 4 analytes: Free SN-38, SN-38 glucuronide, Total SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC_last is defined as area under the serum concentration-time curve from time 0 to time of the last quantifiable concentration of the 4 analytes. | Days 1 and 8 | 
| PK Parameter: AUC_0-168 of Free SN-38, SN-38 Glucuronide, Total SN-38, and Sacituzumab Govitecan-hziy | AUC_0-168 will be determined for 4 analytes: Free SN-38, SN-38 glucuronide, Total 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. | Days 1 and 8 | 
| Percentage of Participants who Develop Positive Anti-Sacituzumab Govitecan-hziy Antibodies |  | Day 1 (Predose) and Day 22 |