Study of Sacituzumab Govitecan in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread

Официальное название

A Phase II Open-Label Study of Sacituzumab Govitecan in Unresectable Locally Advanced/Metastatic Urothelial Cancer

Обзор

The objective of this study is to evaluate the efficacy and safety of sacituzumab govitecan-hziy monotherapy and with novel combinations in participants with metastatic urothelial cancer (mUC).

Подробное описание

Non-Randomized for Cohorts 1,2,3, and 4; Randomized for Cohorts 5, 6, and 7. Cohort 5 has been cancelled, effective December 2023.

Вмешательства

• Препарат Sacituzumab Govitecan-hziy
  Administered intravenously.
• Препарат Pembrolizumab
  Administered per package insert
• Препарат Cisplatin
  Administered per package insert
• Препарат Avelumab
  Administered per package insert
• Препарат Zimberelimab
  Administered intravenously
• Препарат Carboplatin
  Administered per package insert
• Препарат Gemcitabine
  Administered per package insert
• Препарат Domvanalimab
  Administered intravenously
• Препарат Enfortumab Vedotin
  Administered intravenously

Первичные конечные точки

• Overall Response Rate (ORR) Based on Central Review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria (Cohorts 1 to 4 and 6) [Срок оценки: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))]
• Progression free survival (PFS) Based on Central Review by RECIST 1.1 criteria (Cohort 5) [Срок оценки: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))]
• ORR Based on Investigator Review by RECIST 1.1 Criteria (Cohort 7) [Срок оценки: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))]
• Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) (Cohort 7) [Срок оценки: First dose date up to last dose date plus 30 days (approximately 3 years)]
• Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities (Cohort 7) [Срок оценки: First dose date up to last dose date plus 30 days (approximately 3 years)]

Вторичные конечные точки (7)

• Overall Response Rate (ORR) [Срок оценки: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))]
• Duration of Response (DOR) [Срок оценки: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))]
• Progression-Free Survival (PFS) [Срок оценки: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))]
• Overall Survival (OS) [Срок оценки: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))]
• Clinical Benefit Rate (CBR) [Срок оценки: Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))]
• Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) (Cohorts 3, 4, 5, and 6) [Срок оценки: First dose date up to last dose date plus 30 days (approximately 3 years)]
• Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities (Cohorts 3, 4, 5, and 6) [Срок оценки: First dose date up to last dose date plus 30 days (approximately 3 years)]

Критерии участия

Критерии включения

Inclusion Criteria for All Cohorts:

• Female or male individuals, ≥ 18 years of age (19 Years old for South Korea).
• Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1.
• Adequate renal and hepatic function.
• Adequate hematologic parameters without transfusional support.
• Individuals must have a 3-month life expectancy.

Additional Inclusion Criteria for Cohorts 1 to 6:

• Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin):

• Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;
• Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive urothelial cancer, with recurrence/progression ≤12 months following completion of therapy.
• Cohort 1: In addition to above criterion, have had progression or recurrence of urothelial cancer following receipt of an Anti-programmed Cell Death Protein 1 (anti-PD-1)/ Anti-programmed Death Ligand 1 (PD-L1) therapy.
• Cohort 2: Were ineligible for platinum-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease with anti-PD-1/PD-L1 therapy. Individual may not have received any platinum for treatment of recurrent, metastatic or advanced disease.
• Cohort 3: Progression or recurrence of UC following a platinum containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy.
• Cohort 4: Individual has not received any platinum-based chemotherapy in the metastatic or unresectable locally advanced setting. Creatinine clearance of at least 50 mL/min calculated by Cockcroft-Gault formula or another validated tool. For individuals receiving cisplatin at 70 mg/m\^2 on Day 1 of every 21-day cycle, a creatinine clearance of least 60 mL/min calculated by Cockcroft -Gault formula or another validated tool is required. Individuals with creatinine clearance between 50 to 59 mL/min are to receive a split dose of cisplatin (35 mg/m\^2 Day 1 and Day 8 of every 21-day cycle).
• Cohorts 4, 5, 6: Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
• Cohort 5: Individuals received at least 4 cycles and no more than 6 cycles of GEM + cisplatin. No other chemotherapy regimens are allowed in this cohort, with the exception of prior adjuvant or neoadjuvant systemic therapy with curative intent after > 12 months from completion of therapy.
• No evidence of progressive disease following completion of first-line chemotherapy (ie, CR, PR, or SD per RECIST v1.1 guidelines as per investigator).
• Treatment-free interval of 4 to 10 weeks since the last dose of chemotherapy.
• Cohort 6: Cis-ineligible and no prior therapy for metastatic disease or for unresectable locally advanced disease. Checkpoint inhibitor therapy naïve or >12 months from completion of adjuvant therapy are permitted.
• Cohorts 4 and 6: Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Cohorts 1, 2, 3 and 5: Creatinine clearance ≥ 30 mL/min as calculated by the Cockcroft-Gault formula unless otherwise specified

Additional Inclusion Criteria for Cohort 7:

• No prior systemic therapy for locally advanced or metastatic UC. Therapy in the curative setting is allowed provided recurrence is > 12 months since the last dose of systemic therapy.
• Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
• Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

Критерии исключения

Exclusion Criteria for All cohorts:

• Females who are pregnant or lactating.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has an active second malignancy.
• Has known active Hepatitis B or Hepatitis C.
• Has other concurrent medical or psychiatric conditions.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has an active second malignancy.

Additional Exclusion Criteria for Cohorts 1 to 6:

• For Cohort 5: Alopecia, sensory neuropathy Grade ≤2 is acceptable, or other Grade << 2 adverse events not constituting a safety risk based on the investigator's judgment are acceptable.
• Cohort 3: Has received anti-PD-1/PD-L1 therapy previously.
• Cohorts 3 to 6: Has an active autoimmune disease that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Cohorts 3 to 6: Has received a live vaccine within 30 days prior to the first dose of study drug(s), has history or evidence of interstitial lung disease (ILD) or non-infectious pneumonitis.
• Cohort 4: Refractory to platinum (i.e., relapsed ≤ 12 months after completion of chemotherapy) in the neoadjuvant/adjuvant setting.
• Cohorts 4, 5, and 6: For individuals who received prior CPI, a treatment-free interval >12 months between the last treatment administration and the date of recurrence is required.

Additional Exclusion Criteria for Cohort 7:

• Have had a prior anticancer therapy within 12 months prior to C1D1 or prior radiation therapy within 2 weeks prior to C1D1. Individuals participating in observational studies are eligible. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of investigational product.
• Have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Have a Child-Pugh score of B or C.
• Individuals with uncontrolled diabetes.
• Have active keratitis or corneal ulcerations.
• Participants with ongoing sensory or motor neuropathy Grade ≥ 2.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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 · 37 центров

• The University of Arizona Cancer Center-North Campus — Tucson
• USC/Norris Comprehensive Cancer Center — Los Angeles
• University of California San Francisco — San Francisco
• Rocky Mountain Cancer Centers — Littleton
• Smilow Cancer Hospital at Yale-New Haven — New Haven
• Eastern Connecticut Hematology and Oncology Associates — Norwich
• Mount Sinai Comprehensive Cancer Center — Miami Beach
• Woodlands Medical Specialists, PA — Pensacola
• … и ещё 29 центров

Франция · 21 центр

• Centre Hospitalier Regional Universitaire (CHRU) de Besancon, Hopital Jean Minjoz — Besançon
• Hopital Saint Andre (CHU de Bordeaux) — Bordeaux
• Centre Hospitalier Regional Universitaire Brest — Brest
• Centre Jean Perrin — Clermont-Ferrand
• Centre Hospitalier Departmental (CHD) Vendee — La Roche-sur-Yon
• Centre Oscar Lambret — Lille
• Centre Leon Berard — Lyon
• Institut Paoli Calmettes — Marseille
• … и ещё 13 центров

Испания · 18 центров

Список центров уточняется — проверьте первичный протокол.

Германия · 15 центров

• Urologicum Duisburg — Duisburg
• Centrum fur Hamatologie und Onkologie Bethanien — Frankfurt
• Universitätsklinikum Frankfurt, Klinik für Urologie — Frankfurt
• Universitatsklinikum Freiburg — Freiburg im Breisgau
• Universitatsklinikum Hamburg-Eppendorf — Hamburg
• University Hospital Heidelberg — Heidelberg
• Marien Hospital Herne — Herne
• Universitatsklinikum Jena — Jena
• … и ещё 7 центров

South Korea · 14 центров

Список центров уточняется — проверьте первичный протокол.

Италия · 13 центров

• Ospedale San Donato — Arezzo
• Centro di Riferimento Oncologico IRCCS — Aviano
• … и ещё 11 центров

Turkey (Türkiye) · 8 центров

Список центров уточняется — проверьте первичный протокол.

Греция · 5 центров

• Henry Dunant Hospital Center, 4th Oncology Department — Athens
• University General Hospital of Ioannina, Oncology Department — Ioannina
• Athens Medical Center, Oncology Department — Marousi
• General Hospital of Patras Agios Andreas — Pátrai
• Anassa General Clinic, Oncology-Chemotherapy Department — Volos

Великобритания · 4 центра

Список центров уточняется — проверьте первичный протокол.

Публикации

• Petrylak DP, Tagawa ST, Jain RK, Bupathi M, Balar A, Kalebasty AR, George S, Palmbos P, Nordquist L, Davis N, Ramamurthy C, Sternberg CN, Loriot Y, Agarwal N, Park C, Tonelli J, Vance M, Zhou H, Grivas P. TROPHY-U-01 Cohort 2: A Phase II Study of Sacituzumab Govitecan in Cisplatin-Ineligible Patients With Metastatic Urothelial Cancer Progressing After Previous Checkpoint Inhibitor Therapy. J Clin PMID 39186707
• Loriot Y, Kalebasty AR, Flechon A, Jain RK, Gupta S, Bupathi M, Beuzeboc P, Palmbos P, Balar AV, Kyriakopoulos CE, Pouessel D, Sternberg CN, Tonelli J, Sierecki M, Zhou H, Grivas P, Barthelemy P, Bangs R, Tagawa ST. A plain language summary of the TROPHY-U-01 study: sacituzumab govitecan use in people with locally advanced or metastatic urothelial cancer. Future Oncol. 2024;20(23):1621-1631. doi: PMID 38682560
• Grivas P, Pouessel D, Park CH, Barthelemy P, Bupathi M, Petrylak DP, Agarwal N, Gupta S, Flechon A, Ramamurthy C, Davis NB, Recio-Boiles A, Sternberg CN, Bhatia A, Pichardo C, Sierecki M, Tonelli J, Zhou H, Tagawa ST, Loriot Y. Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort PMID 38261969
• Tagawa ST, Balar AV, Petrylak DP, Kalebasty AR, Loriot Y, Flechon A, Jain RK, Agarwal N, Bupathi M, Barthelemy P, Beuzeboc P, Palmbos P, Kyriakopoulos CE, Pouessel D, Sternberg CN, Hong Q, Goswami T, Itri LM, Grivas P. TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhib PMID 33929895

Идентификаторы

NCT: NCT03547973 · IMMU-132-06 · 2023-508302-24

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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