Clinical trial NCT04617522: Study of Sacituzumab Govitecan in Participants With Advanced or Metastatic Solid Tumor and Moderate Liver Impairment
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumor
Liver Failure
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2020-11-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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 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 (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 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.

Primary outcomes:
measure: Percentage of Participants experiencing Treatment Emergent Adverse Events (TEAEs) and Serious AEs
timeFrame: First dose date up to Day 38
measure: Percentage of Participants Experiencing Any Dose Limiting Toxicities (DLTs)
timeFrame: Up to Day 22 (for participants receiving SG on Day 1); Up to Day 28 (for participants receiving SG on Day 8)
measure: Percentage of Participants Experiencing Any Clinically Significant Laboratory Abnormalities
timeFrame: First dose date up to Day 38
measure: Pharmacokinetic (PK) Parameter: Cmax of Free SN-38 and Sacituzumab Govitecan-hziy
timeFrame: Days 1 and 8
measure: PK Parameter: AUC 0-168 of Free SN-38 and Sacituzumab Govitecan-hziy
timeFrame: Days 1 and 8
measure: Percentage of Participants who Develop Anti-Sacituzumab Govitecan-hziy Antibodies
timeFrame: Day 1 (Predose) and Day 22
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Austin
country: United States
facility: NEXT Austin
state: Texas
city: Houston
country: United States
facility: Oncology Consultants, P.A.
state: Texas
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Liver Institute
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Bordeaux
country: France
facility: Institut Bergonie Medical Oncology
city: Lyon
country: France
facility: Centre Leon Berard
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Goldenberg DM. Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys. Clin Cancer Res. 2011 May 15;17(10):3157-69. doi: 10.1158/1078-0432.CCR-10-2939. Epub 2011 Mar 3.
citation: Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Arrojo R, Liu D, Rossi EA, Chang CH, Goldenberg DM. Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. Bioconjug Chem. 2015 May 20;26(5):919-31. doi: 10.1021/acs.bioconjchem.5b00223. Epub 2015 May 8.
citation: Cardillo TM, Sharkey RM, Rossi DL, Arrojo R, Mostafa AA, Goldenberg DM. Synthetic Lethality Exploitation by an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132, Plus PARP Inhibitors in BRCA1/2-wild-type Triple-Negative Breast Cancer. Clin Cancer Res. 2017 Jul 1;23(13):3405-3415. doi: 10.1158/1078-0432.CCR-16-2401. Epub 2017 Jan 9.
citation: Goldenberg DM, Cardillo TM, Govindan SV, Rossi EA, Sharkey RM. Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget. 2015 Sep 8;6(26):22496-512. doi: 10.18632/oncotarget.4318.
citation: Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.
citation: Kwapisz D. Sacituzumab Govitecan-hziy in Breast Cancer. Am J Clin Oncol. 2022 Jul 1;45(7):279-285. doi: 10.1097/COC.0000000000000919. Epub 2022 May 12.