Study of REGN4018 (Ubamatamab) Administered Alone or in Combination With Cemiplimab in Adult Patients With Recurrent Ovarian Cancer or Other Recurrent Mucin-16 Expressing (MUC16+) Cancers

Официальное название

A Phase 1/2 Study of REGN4018 (Ubamatamab), a MUC16×CD3 Bispecific Antibody, Administered Alone or in Combination With Cemiplimab in Patients With Recurrent Ovarian Cancer or Other Recurrent MUC16+ Cancers

Обзор

The main purpose of this study is to: * Learn about the safety of ubamatamab and to find out what dose of ubamatamab can be given alone or with cemiplimab to patients with ovarian cancer or cancer of the uterus * The study will also look at the levels of ubamatamab and/or cemiplimab in the body and measure how well the body can remove the study drug(s). This is called pharmacokinetics * The study will also look at any signs that ubamatamab alone or with cemiplimab can treat recurrent advanced ovarian cancer or cancer of the uterus * To find out how safe and tolerable pretreatment is in combination with ubamatamab and to see how well it works to prevent or minimize Cytokine Release Syndrome (CRS)

Вмешательства

• Препарат Ubamatamab
  Administered per the protocol
• Препарат Cemiplimab
  Administered per the protocol
• Препарат Sarilumab
  Administered per the protocol
• Препарат Tocilizumab
  Administered per the protocol

Первичные конечные точки

• Number of participants with Dose-limiting toxicity (DLTs) for ubamatamab monotherapy [Срок оценки: From Cycle 1, Day 1 up to 35 days]
• Number of participants with DLTs for ubamatamab with cemiplimab [Срок оценки: From Cycle 2, Day 1 up to 21 days]
• Number of participants with Treatment-emergent adverse event (TEAE)s (including immune-related adverse events (imAEs)) for ubamatamab monotherapy [Срок оценки: Up to 2 years]
• Number of participants with TEAEs (including imAEs) for ubamatamab with cemiplimab [Срок оценки: Up to 2 years]
• Number of participants with serious adverse events (SAEs) for ubamatamab monotherapy [Срок оценки: Up to 2 years]
• Number of participants with SAEs for ubamatamab with cemiplimab [Срок оценки: Up to 2 years]
• Number of deaths for ubamatamab monotherapy [Срок оценки: Up to 2 years]
• Number of deaths for ubamatamab with cemiplimab [Срок оценки: Up to 2 years]
• Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) for ubamatamab monotherapy [Срок оценки: Up to 2 years]
• Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab with cemiplimab [Срок оценки: Up to 2 years]

Вторичные конечные точки (12)

• ORR based on RECIST 1.1 for ubamatamab monotherapy [Срок оценки: Up to 2 years]
• ORR based on RECIST 1.1 for ubamatamab with cemiplimab [Срок оценки: Up to 2 years]
• Number of participants with TEAEs (including imAEs) for ubamatamab monotherapy [Срок оценки: Up to 2 years]
• Number of participants with TEAEs (including imAEs) for ubamatamab with cemiplimab [Срок оценки: Up to 2 years]
• Number of participants with SAEs for ubamatamab monotherapy [Срок оценки: Up to 2 years]
• Number of participants with SAEs for ubamatamab with cemiplimab [Срок оценки: Up to 2 years]
• Number of deaths for ubamatamab monotherapy [Срок оценки: Up to 2 years]
• Number of deaths for ubamatamab with cemiplimab [Срок оценки: Up to 2 years]
• Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab monotherapy [Срок оценки: Up to 2 years]
• Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab with cemiplimab [Срок оценки: Up to 2 years]
• Concentration of ubamatamab in serum over time for ubamatamab monotherapy [Срок оценки: Up to 2 years]
• Concentration of ubamatamab in serum over time for ubamatamab with cemiplimab [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• Ovarian Cancer Cohorts Only: Patients with histologically or cytologically confirmed diagnosis of advanced, epithelial ovarian cancer (except carcinosarcoma), primary peritoneal, or fallopian tube cancer who have all of the following:

• serum CA-125 level ≥2 x upper limit of normal (ULN) (in screening, not required for low-grade serous carcinoma)
• has received at least 1 line of platinum-containing therapy or must be platinum-intolerant (applicable for dose escalation and non-randomized dose expansion cohorts)
• documented relapse or progression on or after the most recent line of therapy
• no standard therapy options likely to convey clinical benefit
• Adequate organ and bone marrow function as defined in the protocol
• Life expectancy of at least 3 months
• Randomized phase 2 expansion cohort (Ovarian Cancer only): Platinum-resistant ovarian cancer patients who have had 2 to 4 lines of platinum-based therapy as defined in the protocol.
• Endometrial Cancer Cohorts Only: histologically confirmed endometrial cancer that has progressed or recurrent after prior anti-Programmed Cell Death Ligand 1 (PD-1) therapy and platinum-based chemotherapy:

• MUC16 positivity of tumor cells ≥25% by immunohistochemistry (IHC), as defined in the protocol
• 1-4 prior lines of systemic therapy, as described in the protocol

Критерии исключения

• Prior treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy, as described in the protocol
• Ovarian Cancer Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy (does not apply to low-grade serous ovarian cancer cohort)
• Prior treatment with a MUC16 - targeted therapy
• Untreated or active primary brain tumor, central nervous system (CNS) metastases, or spinal cord compression, as described in the protocol
• History and/or current cardiovascular disease, as defined in the protocol
• Severe and/or uncontrolled hypertension at screening. Patients taking anti-hypertensive medication must be on a stable anti-hypertensive regimen

Note: Other protocol-defined Inclusion/Exclusion Criteria apply

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 11 центров

• University of Alabama_6th Ave — Birmingham
• Massachusetts General Hospital — Boston
• Dana Farber / Harvard Cancer Center — Boston
• Mayo Clinic - Rochester — Rochester
• Roswell Park Cancer Institute — Buffalo
• Columbia University Medical Center — New York
• Memorial Sloan Kettering Cancer Center — New York
• The Ohio State University Wexner Medical Center — Columbus
• … и ещё 3 центра

Испания · 8 центров

• Clinica Universidad de Navarra — Pamplona
• Institut Catala dOncologia Badalona — Badalona
• Hospital Universitari Vall d'Hebron — Barcelona
• Institut Catala d'Oncologia — Barcelona
• Clinica Universidad Navarra (CUN) Madrid — Madrid
• Fundacion Jimenez Diaz — Madrid
• Hospital Universitario San Carlos — Madrid
• Hospital Clinico Universitatio Santiago de Compostela — Santiago de Compostela

Великобритания · 7 центров

• University of Oxford — Oxford
• Royal Marsden Hospital - Sutton — Sutton
• The Royal Marsden NHS Foundation Trust — Sutton
• University College London Hospitals — London
• Guys Hospital — London
• Imperial College Healthcare NHS Trust — London
• The Christie NHS Foundation Trust — Manchester

Франция · 6 центров

• Hopital Lyon Sud — Pierre-Bénite
• Centre Georges Francois Leclerc — Dijon
• Institut Bergonie — Bordeaux
• Centre Francois Baclesse (CFB) — Caen
• Centre Antoine Lacassagne — Nice
• Institut Gustave Roussy — Villejuif

South Korea · 5 центров

• Yonsei University Health System — Seoul
• Asan Medical Center, Univ. of Ulsan — Seoul
• Samsung Medical Center — Seoul
• Korea University Guro Hospital — Seoul
• Seoul National University Hospital — Seoul

Италия · 4 центра

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Rome
• Humanitas S. Pio X — Milan
• Istituto Europeo di Oncologia — Milan
• Instituto Nazionale Tumori- Fondazione Pascale — Naples

Бельгия · 3 центра

• Universitair Ziekenhuis Antwerpen — Edegem
• Grand Hopital de Charleroi — Charleroi
• UZLeuven — Leuven

Израиль · 3 центра

• Rambam Health Care Campus — Haifa
• Sharet Institute of Oncology — Jerusalem
• Sheba Medical Center — Tel Litwinsky

Нидерланды · 3 центра

• Radboudumc — Nijmegen
• Erasmus MC — Rotterdam
• University Medical Center Groningen — Groningen

Австралия · 2 центра

• Prince of Wales Hospital — Randwick
• Peter MacCallum Cancer Center — Melbourne

Публикации

• Zhu M, Madia P, Crawford A, Brouwer-Visser J, Krueger P, Haber L, Peterman M, Uldrick TS, Miller E, Davis JD, Retter MW. Translational findings support regimen selection for first-in-human study of ubamatamab (MUC16 x CD3 bispecific antibody) in patients with recurrent ovarian cancer. Clin Transl Sci. 2024 Dec;17(12):e70082. doi: 10.1111/cts.70082. PMID 39652449

Идентификаторы

NCT: NCT03564340 · R4018-ONC-1721 · 2024-510783-23-00 · 2019-003298-24

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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