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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Sacituzumab Govitecan-hziy
  Administered intravenously

Первичные конечные точки

• Percentage of Participants experiencing Treatment Emergent Adverse Events (TEAEs) and Serious AEs [Срок оценки: First dose date up to Day 38]
• Percentage of Participants Experiencing Any Dose Limiting Toxicities (DLTs) [Срок оценки: 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 [Срок оценки: First dose date up to Day 38]
• Pharmacokinetic (PK) Parameter: Cmax of Free SN-38 and Sacituzumab Govitecan-hziy [Срок оценки: Days 1 and 8]
• PK Parameter: AUC 0-168 of Free SN-38 and Sacituzumab Govitecan-hziy [Срок оценки: Days 1 and 8]
• Percentage of Participants who Develop Anti-Sacituzumab Govitecan-hziy Antibodies [Срок оценки: Day 1 (Predose) and Day 22]

Критерии участия

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 8 центров

• Pacific Shores Medical Group — Long Beach
• Christiana Care Health Services — Newark
• University of Maryland — Baltimore
• NEXT Austin — Austin
• Oncology Consultants, P.A. — Houston
• The University of Texas M.D. Anderson Cancer Center — Houston
• Texas Liver Institute — San Antonio
• NEXT Oncology — San Antonio

Франция · 3 центра

• Institut Bergonie Medical Oncology — Bordeaux
• Centre Leon Berard — Lyon
• Institut de Cancerologie de l'Ouest (ICO) - Saint-Herblain — Saint-Herblain

Италия · 2 центра

• Instituto Europeo di Oncologia — Milan
• Istituto Nazionale Tumori IRCCS Fondazione G. Pascale — Naples

Испания · 2 центра

• Institut Català d'Oncologia - L'Hospitalet de Llobregat — Barcelona
• Hospital Universitario Virgen del Rocío — Seville

Публикации

• 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. PMID 21372224
• 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. PMID 25915780
• 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. PMID 28069724
• 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. PMID 26101915
• Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580. PMID 1244564
• 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. PMID 35728046

Идентификаторы

NCT: NCT04617522 · IMMU-132-15 · 2022-501508-82

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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