A Study of JMT203 in Patients With Cancer Cachexia

Официальное название

A Phase Ia/II, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of JMT203 in Patients With Cancer Cachexia

Обзор

A Phase Ia/II, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of JMT203 in Patients with Cancer Cachexia

Подробное описание

This is a study of JMT203 in patients with cancer cachexia, comprising two parts: Phase Ia, which involves a dose-escalation and dose-expansion study of JMT203 in patients with cancer cachexia, and Phase II, which is a multicenter, randomized, double-blind, placebo-controlled clinical study. The phase II stage includes three cohorts: Cohort A (participants with colorectal cancer cachexia), Cohort B (participants with pancreatic cancer cachexia), and Cohort C (participants with cachexia from other solid tumors) . The primary objectives of Phase Ia are to assess the safety/tolerability of JMT203 in patients with cancer cachexia and to determine the maximum tolerated dose (MTD) (if any) and/or the recommended dose for expansion (RDE) of JMT203. In Phase II, the primary objectives include evaluating the preliminary efficacy of JMT203 at doses of 50 mg and 150 mg versus placebo over a 12-week treatment period and determining the recommended Phase 3 dose (RP3D) of JMT203.

Вмешательства

• Препарат JMT203 Injection
  Drug：JMT203 Injection * Anti-GFRAL monoclonal antibody * Will be injected subcutaneously once per cycle (3 weeks, on Day 1) for 12 weeks, or will be injected subcutaneously once per cycle (3 weeks, on Day 1).
• Препарат JMT203 Injection
  Drug：JMT203 Injection * Anti-GFRAL monoclonal antibody * Will be injected subcutaneously once per cycle (3 weeks, on Day 1) for 12 weeks, or will be injected subcutaneously once per cycle (3 weeks, on Day 1).

Первичные конечные точки

• Phase Ia: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs). [Срок оценки: Up to 90 days after the last dose of JMT203]
• Phase Ia: Incidence of dose-limiting toxicity (DLT) events [Срок оценки: Up to 21 days after the first dose of JMT203]
• Phase Ia: MTD (if applicable). [Срок оценки: Up to 90 days post last dose]
• Phase Ia: RDE. [Срок оценки: Up to 90 days post last dose]
• Phase Ib: Average change in body weight from baseline at each assessment timepoint within 12 weeks. [Срок оценки: Within 12 weeks from baseline]
• Phase II: RP3D [Срок оценки: Approximately 1 year from baseline]

Вторичные конечные точки (12)

• Phase Ia: Area under the curve from time "0" to the time of the last measurable concentration (AUC0-t) of JMT203 [Срок оценки: Up to 90 days after the last dose of JMT203]
• Phase Ia: Maximum measured plasma concentration (Cmax) of JMT203 [Срок оценки: Up to 90 days after the last dose of JMT203]
• Phase Ia: Time when Cmax occurred (Tmax) of JMT203 [Срок оценки: Up to 90 days after the last dose of JMT203]
• Phase Ia: Incidence of anti-drug antibodies (ADA). [Срок оценки: Up to 90 days after the last dose of JMT203]
• Phase Ia: Average change in body weight from baseline at each assessment timepoint within 12 weeks. [Срок оценки: Within 12 weeks from baseline]
• Phase II: Average change in the skeletal muscle index (SMI) of the third lumbar vertebra, measured by computed tomography (CT), from baseline to 12 weeks. [Срок оценки: Within 12 weeks from baseline]
• Phase II: Average change in the severity of anorexia (based on the Functional Assessment of Anorexia/Cachexia Therapy - Anorexia/Cachexia Subscale [FAACT-A/CS]) from baseline to each assessment timepoint. [Срок оценки: Within 12 weeks from baseline]
• Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs). [Срок оценки: Up to 90 days after the last dose of JMT203]
• Phase II: Blood concentration of JMT203; [Срок оценки: Up to 90 days after the last dose of JMT203]
• PhaseII: Incidence of ADA. [Срок оценки: Up to 90 days after the last dose of JMT203]
• PhaseII: Objective Response Rate （ORR） [Срок оценки: Approximately 12 weeks from baseline]
• PhaseII: Progression-Free Survival (PFS) [Срок оценки: Approximately 1 year from baseline]

Критерии участия

Критерии включения

Критерии включения

• Age ≥ 18 years old;
• Voluntarily participate in the study and sign the informed consent form;

Критерии включения

• Age ≥ 18 years old;
• Voluntarily participate in the study and sign the informed consent form;
• Malignant solid tumors confirmed histologically or cytologically, with ongoing or completed anti-tumor treatment, and no significant tumor progression within 28 days prior to the first drug administration，and the investigator estimates that the participant will not require a switch to another anticancer therapy due to disease progression during the first treatment cycle (21 days). For the Phase II portion:

• Cohort A (participants with colorectal cancer cachexia): Must meet the following treatment status: currently receiving or about to initiate investigator-selected second-line standard anticancer therapy, with no more than 5 cycles of second-line therapy, and not suitable for immune checkpoint inhibitors.;
• Cohort B (participants with pancreatic cancer cachexia): Must meet the following treatment status: currently receiving or about to initiate investigator-selected first-line standard anticancer therapy, with no more than 3 cycles of first-line therapy, and not suitable for targeted therapy.;
• Cohort C (participants with cachexia from other solid tumors): Currently receiving or have completed investigator-selected standard anticancer therapy, with no more than three prior lines of therapy.
• Diagnosed with cancer cachexia according to the criteria of the 2011 International Consensus on Cancer Cachexia: Definition and Classification, combined with characteristics of the Chinese population, i.e., presenting with one of the following within 6 months (previous weight data must be supported by written documentation approved by the sponsor): involuntary weight loss >5%, or weight loss >2% when Body Mass Index （BMI） <18.5 kg/m²;
• Adequate organ function, meeting relevant laboratory test standards （without transfusion or hematopoietic growth factor support within 14 days prior to testing）:
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: ≤1;
• 7\. Eastern Cooperative Oncology Group Performance Status （ECOG PS）score: ≤2;
• Estimated survival ≥4 months;
• Fertile eligible patients must use adequate contraceptive measures from the time of signing the informed consent form until 6 months after the last drug administration; female patients of childbearing age must have a negative serum pregnancy test within 7 days before the first drug administration.

Критерии исключения

• Presence of reversible causes leading to decreased food intake;
• Patients with dysphagia or poor food digestion and absorption, including gastrointestinal obstruction, active inflammatory bowel disease, or short bowel syndrome;
• Patients with cachexia caused by clearly identified other causes, such as severe chronic obstructive pulmonary disease, uncontrolled thyroid disease, vital organ failure, or Acquired Immune Deficiency Syndrome （AIDS）;
• Patients receiving tube feeding or parenteral nutrition therapy during the screening period;
• Patients who have taken any prescription medications for appetite enhancement or improve weight loss within 28 days or 5 half-lives (whichever is shorter) before the first study drug administration, including but not limited to anamorelin, medroxyprogesterone acetate, dronabinol, medical marijuana, etc.;
• Initiation of systemic glucocorticoids (prednisone >10 mg/day or equivalent doses of other similar drugs) or other immunosuppressive therapies within 28 days before the first study drug administration, excluding pretreatment for antitumor therapy;
• Patients with a BMI exceeding 30 kg/m²;
• Patients who have undergone major surgery within 4 weeks before the first study drug administration and have not recovered, or are expected to undergo major surgery during the study;
• Patients who have received other clinical study medications within 4 weeks or 5 half-lives (whichever is shorter) before the first study drug administration;
• Patients with severe infections requiring intravenous antibiotics, antivirals, or antifungals during the screening period;
• Patients with difficult-to-control moderate to large amounts of serous cavity effusion, such as pericardial effusion or pleural/abdominal/pelvic effusion, within 14 days before the first study drug administration;
• Patients with a second primary active malignancy within 2 years before the first study drug administration, excluding locally curable tumors that have undergone radical treatment (e.g., resected basal cell or squamous cell skin cancer, superficial bladder cancer, breast carcinoma in situ);
• Patients with active central nervous system metastases (brain metastases, carcinomatous meningitis, and spinal cord metastases), except for those with controlled lesions confirmed by imaging studies within 28 days before the first use of the investigational product;
• History of severe cardiovascular disease, including but not limited to:

• Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, second- or third-degree atrioventricular block, etc.;
• Occurrence of acute coronary syndrome, congestive heart failure, stroke, or other cardiovascular events of grade 3 or higher within 6 months before the first study drug administration;
• New York Heart Association functional class ≥III or left ventricular ejection fraction (LVEF) <50%;
• Patients with severe immune deficiency or a history of organ transplantation;
• Patients with recent (within the past year) or current depression or suicidal ideation/tendencies;
• Known allergy to JMT203 or its components;
• History of severe allergic reactions or uncontrollable allergic asthma;
• Patients deemed unsuitable for participation in this clinical study by the investigator for other reasons.

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

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sir run run shaw Hospital — Zhejiang

Идентификаторы

NCT: NCT06868849 · JMT203-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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