A Study of JNJ-88549968 for the Treatment of Calreticulin (CALR)-Mutated Myeloproliferative Neoplasms

Официальное название

A First-in-Human Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-88549968, a T-cell Redirecting Bispecific Antibody for CALR-mutated Myeloproliferative Neoplasms

Обзор

The purpose of this study is to characterize safety and to determine the Recommended Phase 2 Dose (RP2D\[s\]) and optimal dosing schedule(s) of JNJ-88549968 in part 1 (Dose Escalation); to characterize the safety of JNJ- 88549968 at RP2D(s) in part 2 (Cohort Expansion). For U.S. sites: the purpose of this study is to characterize the safety and to determine the RP2D(s) and optimal dosing schedule(s) of JNJ-88549968 in Part 1 and part 1b (Dose Escalation), and to characterize the safety of JNJ-88549968 at the RP2D(s) in Part 2 and part 2b (Cohort Expansion), when given as monotherapy in essential thrombocythemia (ET) or myelofibrosis (MF), and with ruxolitinib or momelotinib in MF only.

Вмешательства

• Препарат JNJ-88549968
  JNJ-88549968 will be administered.
• Препарат Ruxolitinib
  For US sites: Ruxolitinib will be administered for participants with MF only.
• Препарат Momelotinib
  For US sites: Momelotinib will be administered for participants with MF only.

Первичные конечные точки

• Part 1, Part 1b (US Only): Number of Participants With Dose Limiting Toxicity (DLT) [Срок оценки: Approximately up to 35 days after first dose of study treatment]
• Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs) [Срок оценки: Up to 2 years]
• Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs) by Severity [Срок оценки: Up to 2 years]

Вторичные конечные точки (7)

• Part 1, 2, Part 1b (US Only), Part 2b (US Only): Serum Concentration of JNJ-88549968 [Срок оценки: Up to 2 years]
• Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants With Presence of Anti-Drug Antibodies to JNJ-88549968 [Срок оценки: Up to 2 years]
• Part 1, 2, Part 1b (US Only), Part 2b (US Only): Overall Response Rate [Срок оценки: Up to 2 years]
• Part 1, 2, Part 1b (US Only), Part 2b (US Only): Complete Response (CR) Rate [Срок оценки: Up to 2 years]
• Part 1, 2, Part 1b (US Only), Part 2b (US Only): Time to Response (TTR) [Срок оценки: Up to 2 years]
• Part 1, 2, Part 1b (US Only), Part 2b (US Only): Duration of Response (DOR) [Срок оценки: Up to 2 years]
• Part 2, Part 2b (US Only): Change From Baseline in Myeloproliferative Neoplasm (MPN) Symptom Burden [Срок оценки: Baseline up to 2 years]

Критерии участия

Критерии включения

• Be greater than or equal to (>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever the greater) at the time of informed consent
• Positive for a calreticulin (CALR) driver mutation of essential thrombocythemia (ET) or myelofibrosis (MF)
• Participants with ET and MF with risk characteristics as described in the protocol
• Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of less than or equal to (<=) 2
• For US sites: Eligible for ruxolitinib therapy as per drug label for participants naive to a janus kinase (JAK) inhibitor

Критерии исключения

• Known allergies, hypersensitivity, or intolerance to the excipients of the study treatment
• Concurrent or recently diagnosed or treated malignancies present at the time of participant screening. Exceptions are squamous and basal cell carcinoma of the skin, carcinoma in situ of the cervix, and any malignancy that is considered cured or has minimal risk of recurrence within 1 year of first dose of study treatment in the opinion of both the investigator and sponsor's medical monitor. Participants cured of another malignant disease with no sign of relapse greater than or equal to (>=) 3 years after treatment ended are allowed to enter the study
• Prior solid organ transplantation
• Either of the following regarding hematopoietic stem cell transplantation:

• Prior treatment with allogenic stem cell transplant less than or equal to (<=) 6 months before the first dose of JNJ-88549968 or
• Evidence of graft versus host disease (GVHD) that requires immunosuppressant therapy
• History of clinically significant cardiovascular disease within 6 months prior to the first dose of study treatment

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 13 центров

• City of Hope — Duarte
• UCHealth Cancer Care Anschutz Medical Campus University of Colorado Cancer Center — Aurora
• Moffit Cancer center — Tampa
• Emory University — Atlanta
• University of Michigan — Ann Arbor
• Start Midwest — Grand Rapids
• START New Jersey — East Brunswick
• Memorial Sloan Kettering Cancer Center — New York
• … и ещё 5 центров

Германия · 6 центров

• Universitaetsklinikum der RWTH Aachen — Aachen
• Charite Campus Benjamin Franklin — Berlin
• Med. Universitatsklinik Essen — Essen
• Medizinische Hochschule Hannover — Hanover
• Universitaetsklinikum Heidelberg — Heidelberg
• Universitaetsklinikum Regensburg — Regensburg

Израиль · 4 центра

• Carmel Medical Center — Haifa
• Hadassah University Hospita Ein Kerem — Jerusalem
• Sheba Medical Center — Ramat Gan
• Tel Aviv Sourasky Medical Center — Tel Aviv

Франция · 3 центра

• Hopital Saint Louis — Paris
• CH LYON SUD - Hematology — Pierre-Bénite
• Institut Universitaire du Cancer Toulouse Oncopole — Toulouse

Великобритания · 3 центра

• University College London Hospitals Nhs Foundation Trust — London
• Guy's and St Thomas' Hospital — London
• Churchill Hospital — Oxford

Канада · 2 центра

• Princess Margaret Cancer Centre University Health Network — Toronto
• Jewish General Hospital — Montreal

Китай · 2 центра

• Peking Union Medical College Hospital — Пекин
• Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences — Тяньцзинь

Италия · 2 центра

• Policlinico Sant'Orsola Malpighi — Bologna
• Policlinico di Milano — Milan

Япония · 2 центра

• Juntendo University Hospital — Bunkyō City
• National Cancer Center Hospital East — Kashiwa

Испания · 2 центра

• Hosp. Univ. Germans Trias I Pujol — Badalona
• Hosp. Clinico Univ. de Valencia — Valencia

Идентификаторы

NCT: NCT06150157 · 88549968MPN1001 · 2023-505584-36-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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