A Study to Assess Adverse Events and Change in Disease Activity of Multiple Treatment Combinations With Intravenous Mirvetuximab Soravtansine in Adult Participants With Ovarian Cancer

Официальное название

A Phase 2, Open-Label, Randomized, Master Protocol Dose Optimization Study to Evaluate Safety and Efficacy of Multiple Treatment Combinations With Mirvetuximab Soravtansine in Subjects With Ovarian Cancer

Обзор

Ovarian cancer is a lethal disease with an estimated 310,000 new cases and 200,000 deaths experienced worldwide in 2020. The purpose of this study is to assess the adverse events and change in disease activity of mirvetuximab soravtansine with carboplatin, or bevacizumab (Bev), or bev alone in participants with ovarian cancer (OC). Participants must have confirmation of folate receptor alpha (FRa) positivity by the Ventana folate receptor 1 (FOLR1) Assay. Mirvetuximab Soravtansine (MIRV) is an investigational drug for the treatment of OC. Participants will be assigned to 1 of 3 substudies and further into groups called treatment arms. In substudy 1, arms A-C, participants will receive 1 of 2 doses of MIRV with Bev, or Bev alone. In substudy 2, arms D and E, participants will receive 1 of 2 doses of MIRV with carboplatin, followed by MIRV alone. In substudy 3, arms F and G, participants will receive one of two doses of MIRV with BEV and carboplatin, followed by MIRV with BEV. Approximately 400 participants will be enrolled in the study at 100 sites around the world. Participants will receive intravenously (IV) infused MIRV with IV infused carboplatin, or IV infused Bev, or IV infused carboplatin and Bev, or IV infused Bev alone. The total study duration will be approximately 40 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.

Вмешательства

• Препарат Mirvetuximab Soravtansine
  Intravenous (IV) infusion
• Препарат Bevacizumab
  IV Infusion
• Препарат Carboplatin
  IV Infusion

Первичные конечные точки

• Substudy 1, 2, and 3: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) (any grade, Grade >= 3) [Срок оценки: Up to Approximately 40 Months]
• Substudy 1, 2, and 3: Number of Participants with TEAEs Leading to Discontinuation [Срок оценки: Up to Approximately 40 Months]
• Substudy 1, 2, and 3: Number of Participants with Ocular Adverse Events (AEs) (any grade, Grade >= 2) [Срок оценки: Up to Approximately 40 Months]
• Substudy 1, 2, and 3: Overall Response (OR) as Assessed by the Investigator per RECIST v1.1 [Срок оценки: Up to Approximately 40 Months]
• Substudy 1: Progression free survival (PFS) as Assessed by the Investigator per RECIST v1.1 [Срок оценки: Up to Approximately 40 Months]

Вторичные конечные точки (5)

• Substudy 1, 2, and 3: CA-125 Response per Gynecologic Cancer Intergroup (GCIG) Criteria [Срок оценки: Up to Approximately 40 Months]
• Substudy 1, 2, and 3: Duration of Response (DOR) as Assessed by the Investigator per RECIST v1.1 [Срок оценки: Up to Approximately 40 Months]
• Substudy 1, 2, and 3: Number of Participants with Peripheral Neuropathy AEs (any grade, Grade ≥ 2) [Срок оценки: Up to Approximately 40 Months]
• Substudy 1, 2, and 3: Number of Participants with Adjudicated Pneumonitis/ Interstitial Lung Disease (ILD) (any grade) [Срок оценки: Up to Approximately 40 Months]
• Substudy 2 and 3: PFS as Assessed by the Investigator per RECIST v1.1 [Срок оценки: Up to Approximately 40 Months]

Критерии участия

Критерии включения

Substudy 1

• Participants must be willing to provide an archival tumor tissue block or slides or must undergo a procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα expression as defined by the central VENTANA FOLR1 (FOLR1-2.1) assay. Tumors must have FRα-expression in >= 50% of viable tumor cells with >= 2+ staining intensity.
• Participants must have an Eastern Cooperative Oncology Group performance status of 0 or 1.
• 1L participants must have a confirmed diagnosis of Federation of Gynecology and Obstetrics (FIGO) Stage III or IV high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer.

2L participants must have platinum-sensitive high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Participants must have platinum-sensitive disease defined as radiographic progression greater than 183 days from the last dose of most recent platinumbased chemotherapy. Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression.

• Participant has a local homologous recombination deficient (HRD) or breast cancer susceptibility gene (BRCA) test result available. Participants with BRCA wild-type will need to have a local HRD test result available.

Substudy 2

• Participants must be willing to provide an archival tumor tissue block or slides or must undergo a procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα expression as defined by the central VENTANA FOLR1 (FOLR1-2.1) assay. Tumors must have FRα-expression in >= 50% of viable tumor cells with >= 2+ staining intensity.
• Participants must have an Eastern Cooperative Oncology Group performance status of 0 or 1.
• Participants must have a confirmed diagnosis of high-grade serous ovarian, primary peritoneal, or fallopian tube cancer.
• Participants must have relapsed after 1 or 2 prior lines of platinum-based chemotherapy.
• Participants must have platinum-sensitive disease defined as radiographic progression greater than 183 days from the last dose of platinum-based chemotherapy.
• Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (assessed by the investigator) at baseline.

Substudy 3

• Participants must be willing to provide an archival tumor tissue block or slides or must undergo a procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα expression as defined by the central VENTANA FOLR1 (FOLR1-2.1) assay. Tumors must have FRα-expression in >= 50% of viable tumor cells with >= 2+ staining intensity.
• Participants must have an Eastern Cooperative Oncology Group performance status of 0 or 1.
• Participants must have a confirmed diagnosis of high-grade serous ovarian, primary peritoneal, or fallopian tube cancer.
• Participants must have relapsed after 1 or 2 prior lines of platinum-based chemotherapy.
• Participants must have platinum-sensitive disease defined as radiographic progression greater than 183 days from the last dose of platinum-based chemotherapy.
• Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (assessed by the investigator) at baseline.

Критерии исключения

Substudy 1

• Participants with progressive disease (PD) while on triplet therapy or after the first day of their last triplet therapy cycle and before randomization.
• Participants who receive an intervening dose of bevacizumab after the first day of their last triplet therapy cycle and before randomization.
• Participants who received prior treatment with mirvetuximab soravtansine (MIRV), any FRα-targeting agent, or Poly(ADP-ribose) polymerase inhibitor (PARPi).

Substudy 2

• More than 2 prior lines of chemotherapy. Lines of prior anticancer therapy are counted with the following considerations:

• Neoadjuvant +/- adjuvant therapies are considered 1 line of therapy if the neoadjuvant and adjuvant correspond to 1 fully predefined regimen; otherwise, they are counted as 2 prior regimens.
• Maintenance therapy (e.g., bevacizumab, PARPi) will be considered part of the preceding line of therapy (i.e., not counted independently).
• If a chemotherapeutic agent in a regimen is substituted with another during a course of treatment due to toxicity, it will be considered part of the same line of therapy
• Prior hormonal therapy will not be counted as a separate line of chemotherapy (it will be counted as part of the prior systemic therapy regimen)
• Participants who received prior treatment with mirvetuximab soravtansine or other FRα-targeting agents.

Substudy 3

• More than 2 prior lines of chemotherapy. Lines of prior anticancer therapy are counted with the following considerations:

• Neoadjuvant +/- adjuvant therapies are considered 1 line of therapy if the neoadjuvant and adjuvant correspond to 1 fully predefined regimen; otherwise, they are counted as 2 prior regimens.
• Maintenance therapy (e.g., bevacizumab, PARPi) will be considered part of the preceding line of therapy (i.e., not counted independently).
• If a chemotherapeutic agent in a regimen is substituted with another during a course of treatment due to toxicity, it will be considered part of the same line of therapy
• Prior hormonal therapy will not be counted as a separate line of chemotherapy (it will be counted as part of the prior systemic therapy regimen)
• Participants who received prior treatment with mirvetuximab soravtansine or other FRα-targeting agents.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 27 центров

• UC San Diego Health - Moores Cancer Center /ID# 277574 — La Jolla
• Sansum Clinic - Solvang /ID# 277712 — Solvang
• University of Florida College of Medicine /ID# 278348 — Gainesville
• Orlando Health Cancer Institute Gynecologic Cancer Center - Orlando /ID# 278623 — Orlando
• Florida Cancer Specialists - North /ID# 278626 — St. Petersburg
• Florida Cancer Specialists - East /ID# 278605 — West Palm Beach
• Baptist Health Lexington /ID# 278267 — Lexington
• Our Lady of the Lake Physician Group - Medical Oncology /ID# 277440 — Baton Rouge
• … и ещё 19 центров

Франция · 13 центров

• Strasbourg Oncologie Liberale /ID# 276698 — Strasbourg
• Centre Georges Francois Leclerc /ID# 276737 — Dijon
• Centre Francois Baclesse /ID# 276709 — Caen
• Hopital Prive Des Cotes D'Armor /ID# 276706 — Plérin
• Institut Bergonie /ID# 276696 — Bordeaux
• Institut Curie -Site Saint-Cloud /ID# 276850 — Saint-Cloud
• Institut Godinot /ID# 276849 — Reims
• CHU de Limoges site CHU Dupuytren 1 /ID# 276851 — Limoges
• … и ещё 5 центров

Испания · 13 центров

• Hospital Universitario Marques de Valdecilla /ID# 276415 — Santander
• Hospital Universitario Donostia /ID# 276404 — Donostia / San Sebastian
• Complejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria /ID# 276438 — Las Palmas de Gran Canaria
• Hospital Universitario Puerta de Hierro - Majadahonda /ID# 281304 — Majadahonda
• Hospital Universitario Virgen del Rocio /ID# 276426 — Seville
• Complejo Hospitalario Universitario A Coruna /ID# 276416 — A Coruña
• Hospital Universitari Vall d Hebron /ID# 276478 — Barcelona
• Hospital Clinic de Barcelona /ID# 276412 — Barcelona
• … и ещё 5 центров

Австралия · 10 центров

• St. George Private Hospital /ID# 276570 — Kogarah
• Chris O'Brien Lifehouse /ID# 276337 — Sydney
• Icon Cancer Centre Wesley /ID# 277199 — Auchenflower
• Burnside War Memorial Hospital /ID# 277602 — Adelaide
• Icon Cancer Centre Hobart /ID# 277688 — Hobart
• Monash Health - Monash Medical Centre - Clayton /ID# 276984 — Clayton
• Barwon Health /ID# 277297 — Geelong
• Austin Hospital /ID# 276534 — Melbourne
• … и ещё 2 центра

South Korea · 7 центров

• National Cancer Center /ID# 276283 — Goyang-si
• Seoul National University Bundang Hospital /ID# 276280 — Seongnam-si
• Seoul National University Hospital /ID# 276182 — Seoul
• Yonsei University Health System Severance Hospital /ID# 276266 — Seoul
• Asan Medical Center /ID# 276955 — Seoul
• Samsung Medical Center /ID# 276261 — Seoul
• Korea University Guro Hospital /ID# 276194 — Seoul

Бельгия · 5 центров

• Cliniques Universitaires UCL Saint-Luc /ID# 276321 — Brussels
• AZ Maria Middelares /ID# 276325 — Ghent
• Universitair Ziekenhuis Leuven /ID# 276316 — Leuven
• CHU de Liege /ID# 276500 — Liège
• UCL Namur University Hospital, Site Sainte-Elisabeth /ID# 277183 — Namur

Чехия · 4 центра

• Masarykuv Onkologicky Ustav /ID# 276080 — Brno
• Vseobecna Fakultni nemocnice v Praze /ID# 276213 — Prague
• Fakultni nemocnice Motol a Homolka /ID# 276300 — Prague
• Fakultni nemocnice Hradec Kralove - Sokolska /ID# 276205 — Hradec Králové

Дания · 3 центра

• Herlev Hospital /ID# 276831 — Herlev
• Aalborg University Hospital /ID# 276435 — Aalborg
• Odense University Hospital /ID# 276462 — Odense

Идентификаторы

NCT: NCT07059845 · M25-709 · 2025-521606-18

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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