GM103 Intratumoral Injection in Patients With Locally Advanced, Unresectable, Refractory and/or Metastatic Solid Tumors

Официальное название

A Phase I/II, Open-label, Dose-escalation With Expansion Study of GM103 Via Intratumoral Injection, Alone and in Combination With Pembrolizumab in Adult Patients With Locally Advanced, Unresectable, Refractory and/or Metastatic Solid Tumors

Обзор

The purpose of this study is to measure safety, tolerability, and preliminary antitumor efficacy of GM103 administered alone and in combination with pembrolizumab in patients with locally advanced, unresectable, refractory and/or metastatic solid tumors (including but not limited to head and neck cancer, malignant melanoma, CRC, renal cell carcinoma, cervical cancer, and breast cancer). Study details include:

Подробное описание

Part A, B

* Primary Objectives

* To determine the MTD and RP2D based on safety and tolerability of GM103 as monotherapy. * To evaluate overall safety profile of GM103 as monotherapy. * Secondary Objectives

* To assess preliminary anti-tumor efficacy of GM103 at the RP2D, as monotherapy.

Part C

* Primary Objectives

* To determine the MTD and RP2D based on safety and tolerability of GM103 in combination with pembrolizumab. * To evaluate overall safety profile of GM103 in combination with pembrolizumab . * Secondary Objectives

* To assess preliminary anti-tumor efficacy of GM103 at the RP2D, in combination with pembrolizumab.

Вмешательства

• Препарат GM103 (Part A)
  dose escalation of GM103 as monotherapy, conducted in 12-24 patients. Part A will include a screening period of up to 28 days, a dose limiting toxicity (DLT) evaluation period of the first 2 cycles, and a treatment period from cycles 3-12 (each cycle will consist of 14 days \[2 weeks\]).
• Препарат GM103 (Part B)
  dose expansion study of GM103 as monotherapy, conducted in up to 40 patients (a minimum of 20 patients per target disease \[HNC, CRC\]). Part B of the study will include a screening period of up to 28 days, and 1 to a maximum of 12 treatment cycles (each cycle will consist of 14 days \[2 weeks\]).
• Препарат GM103 and Pembrolizumab (Part C)
  dose-escalation and dose-expansion of GM103 in combination with pembrolizumab, conducted in approximately 61 patients. Part C of the study will include a screening period of up to 28 days, a safety run-in period of 2 cycles (it consists of 2 cohorts and the first 1 cycle for the DLT assessment period of each cohort is included, each cycle will consist of 21 days \[3 weeks\]), and a dose expansion period from cycle 3 to a maximum of 12 treatment cycles (of 21 days \[3 weeks\]).

Первичные конечные точки

• Percentage of patients with DLTs by cohorts [Срок оценки: during the first 28 days of treatment]
• Percentage of patients with DLTs [Срок оценки: during the first 21 days of treatment]
• Incidence of AEs, AESIs, SAEs, AEs leading to discontinuation, and AEs resulting in death [Срок оценки: through study completion, and average 1 year]

Вторичные конечные точки (5)

• ORR [Срок оценки: through study completion, and average 1 year]
• DCR defined as the proportion of patients whose BOR was CR, PR and SD [Срок оценки: through study completion, an average of 1 year]
• Median PFS defined as the time from the date of the first administration of study drug to the date of disease progression or death [Срок оценки: through study completion, an average of 1 year]
• Incidence of GM103 detection [Срок оценки: every cycle, through study completion, an average of 1 year [up to 12 treatment cycles, Part A&B: each cycle will consist of 14 days(2 weeks) / Part C: each cycle will consist of 21 days(3 weeks)]]
• Changes in the level of anti-adenovirus antibodies(ADA) in blood compared to baseline (ADA in genome copies/mL using qPCR) [Срок оценки: every 2 cycles after the first cycle, through study completion, an average of 1 year [up to 12 treatment cycles, Part A&B: each cycle will consist of 14 days(2 weeks) / Part C: each cycle will consist of 21 days(3 weeks)]]

Критерии участия

Критерии включения

• Patient must be 18 years of age or over, at the time of signing the informed consent.
• Have a diagnosis of locally advanced, unresectable, refractory and/or metastatic solid tumors
• Have a tumor that is accessible and is willing to consent to tumor biopsies during the study.
• Have at least one measurable site of disease according to RECIST 1.1 criteria; The lesions should be either previously non irradiated or progressive lesions after irradiation, that can be accurately measured at baseline (for measurable lesions) with computed tomography (CT) or magnetic resonance imaging (MRI).
• Part A, B and C: Have at least one intratumorally injectable lesion (measurable and/or non-measurable based on RECIST 1.1), that can be accurately measured at baseline (for measurable lesions) with computed tomography (CT) or magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET-CT); or clinical examination and which is suitable for repeated measurement.
• Part B and C (only for dose expansion cohort): Have paired pre- and on treatment tumor biopsies for patients with metastases that are safely accessible as determined by the investigator.
• Patients with brain metastasis must have stable disease and must be neurologically asymptomatic and not requiring corticosteroid treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Have a predicted life expectancy of 12 weeks or more.
• Able to comply with study procedures in the Investigator's opinion.
• Adequate organ function determined within 4 weeks prior to screening
• Patient is male or female.
• Contraceptive use by women must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Patient is capable of giving signed informed consent.

Критерии исключения

• Known history or eiciency virus \[HIV\]/acquired immunodeficiency syndrome \[AIDS\]) and/or medication.
• Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisolone equivalent) or other immunosuppressive medications within 14 days of the first dose of study treatment.
• Patients with a history of, or active, known or suspected auto-immune disease or a syndrome that requires systemic or immunosuppressive agents.
• Active infections requiring antibiotics, physician monitoring or recurrent fevers (>38.0 ̊C) associated with a clinical diagnosis of active infection.
• Patient who has a history of seizures, central nervous system abnormalities, mental disorders, and heart disease.
• Patient who has a history of pleural effusion, pulmonary embolism, and intestinal obstruction.
• Treatment with any systemic anticancer therapies for locally advanced or metastatic within 4 weeks or 6 half-lives of prior anticancer therapy, whichever is shorter, prior to initiation of study treatment.
• Previous treated with GM103 or other oncolytic viruses.
• Radiation therapy within 2 weeks prior to enrollment.
• Use of the antiviral agents within 7 days prior to the first dose of study treatment; or pegylated interferon in the 14 days before the first dose of study treatment
• Patients who have received a live vaccine within 30 days of study enrollment.
• Any serious or uncontrolled medical disorder that, in the opinion of the Investigator or the Medical Monitor, may increase the risk associated with study participation or study treatment administration, impair the ability of the patient to receive protocol therapy or interfere with the interpretation of study results.
• Participation of any other clinical trials within 4 weeks prior to first administration of study treatment.
• Administration of an investigational drug in the 28 days before the first dose of study treatment.
• Has an ejection fraction (EF) of 50% or less, based on a multigated acquisition (MUGA) scan or echocardiogram (ECHO).
• Major surgery within 4 weeks prior to enrollment.
• Inability or unwillingness to follow study procedures including drug administration.
• Any serious medical condition or abnormality in clinical laboratory tests

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

South Korea · 4 центра

• National Cancer Center — Goyang-si
• Korea University Anam Hospital — Seoul
• Hanyang University Seoul Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul

Идентификаторы

NCT: NCT06265025 · GM103-CT-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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