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
Overview
- Phase
- Phase 1
- Intervention
- Sacituzumab Govitecan-hziy
- Conditions
- Advanced or Metastatic Solid Tumor
- Sponsor
- Gilead Sciences
- Enrollment
- 30
- Locations
- 13
- Primary Endpoint
- Percentage of Participants experiencing Treatment Emergent Adverse Events (TEAEs) and Serious AEs
- Status
- Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
- •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.
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 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.
Arms & Interventions
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).
Intervention: Sacituzumab Govitecan-hziy
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).
Intervention: Sacituzumab Govitecan-hziy
Outcomes
Primary Outcomes
Percentage of Participants experiencing Treatment Emergent Adverse Events (TEAEs) and Serious AEs
Time Frame: First dose date up to Day 38
Percentage of Participants Experiencing Any Dose Limiting Toxicities (DLTs)
Time Frame: 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
Time Frame: First dose date up to Day 38
Pharmacokinetic (PK) Parameter: Cmax of Free SN-38 and Sacituzumab Govitecan-hziy
Time Frame: 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
Time Frame: 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
Time Frame: Day 1 (Predose) and Day 22