Clinical trial NCT06868849: A Study of JMT203 in Patients With Cancer Cachexia
Official title: An Open-label, Multi-center, Phase I Study to Investigate Safety, Tolerability, Pharmacokinetics, and Efficacy of JMT203 in Patients With Cancer Cachexia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Colorectal Cancer
Non Small Cell Lung Cancer
Pancreatic Cancer
Cancer Cachexia
Lead sponsor: Shanghai JMT-Bio Inc.
Sponsor class: INDUSTRY
First posted: 2025-03-11
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: There is no comparison group.
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter Phase I clinical study aimed at evaluating the safety/tolerability, pharmacokinetics, and effectiveness of JMT203 in patients with cancer cachexia.

Detailed description: 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 Ib, which is a cohort-expansion study of JMT203 in the same patient population. 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 Ib, the primary objectives include evaluating the preliminary efficacy of JMT203 in treating cancer cachexia and determining the recommended Phase 2 dose (RP2D) of JMT203.

Eligibility criteria: Inclusion Criteria:

Inclusion Criteria:

1. Age ≥ 18 years old;
2. Voluntarily participate in the study and sign the informed consent form;
3. 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:

   * Dose escalation and expansion phase (Phase Ia): The investigator predicts that there will be no need to change the anti-tumor treatment regimen due to disease progression within the first dosing cycle (21 days) of this study;
   * Cohort expansion study phase (Phase Ib): Cohorts A/B/C will enroll patients with non-small cell lung cancer, pancreatic cancer, and colorectal cancer, respectively;
4. 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;
5. Serum Growth Differentiation Factor 15 （GDF-15） levels ≥1300 pg/ml within 28 days prior to the first study drug administration (applicable to the cohort expansion phase only);
6. Adequate organ function, meeting relevant laboratory test standards:

   Item Laboratory Test Value Blood Absolute Neutrophil Count ≥1.0×10\^9/L Platelet Count ≥75×10\^9/L Hemoglobin ≥80 g/L Kidney Serum Creatinine ≤1.5×ULN (if \>1.5×ULN, creatinine clearance calculated by the Cockcroft formula must≥30 ml/min) Liver Total Bilirubin ≤1.5×ULN (For patients with liver metastasis, liver cancer, or bile duct obstruction: may be relaxed to ≤3×ULN) AST and ALT ≤3×ULN or ≤5×ULN for patients with liver metastasis Coagulation APTT ≤1.5×ULN INR ≤1.5×ULN Note: ULN = Upper Limit of Normal; if laboratory tests do not meet the criteria, the investigator will determine eligibility based on the patient's overall condition.
7. 7. Eastern Cooperative Oncology Group Performance Status （ECOG PS）score: ≤2;
8. Estimated survival ≥4 months;
9. 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.

Exclusion Criteria:

1. Presence of reversible causes leading to decreased food intake;
2. Patients with dysphagia or poor food digestion and absorption, including gastrointestinal obstruction, active inflammatory bowel disease, or short bowel syndrome;
3. 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）;
4. Patients receiving tube feeding or parenteral nutrition therapy during the screening period;
5. 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.;
6. 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;
7. Patients with a BMI exceeding 30 kg/m²;
8. 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;
9. Patients who have received other clinical study medications within 4 weeks or 5 half-lives (whichever is shorter) before the first study drug administration;
10. Patients with severe infections requiring intravenous antibiotics, antivirals, or antifungals during the screening period;
11. 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;
12. 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);
13. 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;
14. History of severe cardiovascular disease, including but not limited to:

    1. Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, second- or third-degree atrioventricular block, etc.;
    2. 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;
    3. New York Heart Association functional class ≥III or left ventricular ejection fraction (LVEF) \<50%;
15. Patients with severe immune deficiency or a history of organ transplantation;
16. Patients with recent (within the past year) or current depression or suicidal ideation/tendencies;
17. Known allergy to JMT203 or its components;
18. History of severe allergic reactions or uncontrollable allergic asthma;
19. Patients deemed unsuitable for participation in this clinical study by the investigator for other reasons.

Primary outcomes:
measure: Phase Ia: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
timeFrame: Up to 90 days after the last dose of JMT203
measure: Phase Ia: Incidence of dose-limiting toxicity (DLT) events
timeFrame: Up to 21 days after the first dose of JMT203
measure: Phase Ia: MTD (if applicable).
timeFrame: Up to 90 days post last dose
measure: Phase Ia: RDE.
timeFrame: Up to 90 days post last dose
measure: Phase Ib: Average change in body weight from baseline at each assessment timepoint within 12 weeks.
timeFrame: Within 12 weeks from baseline
Secondary outcomes:
measure: Phase Ia: Area under the curve from time "0" to the time of the last measurable concentration (AUC0-t) of JMT203
timeFrame: Up to 90 days after the last dose of JMT203
measure: Phase Ia: Maximum measured plasma concentration (Cmax) of JMT203
timeFrame: Up to 90 days after the last dose of JMT203
measure: Phase Ia: Time when Cmax occurred (Tmax) of JMT203
timeFrame: Up to 90 days after the last dose of JMT203
measure: Phase Ia: The PD indicators include β-hydroxybutyric acid.
timeFrame: Up to 12 weeks
measure: Phase Ia: Incidence of anti-drug antibodies (ADA).
timeFrame: Up to 90 days after the last dose of JMT203
measure: Phase Ia: Average change in body weight from baseline at each assessment timepoint within 12 weeks
timeFrame: Within 12 weeks from baseline
measure: Phase Ib: Average change in the skeletal muscle index (SMI) of the third lumbar vertebra, measured by computed tomography (CT), from baseline to 12 weeks.
timeFrame: Within 12 weeks from baseline
measure: Phase Ib: 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.
timeFrame: Within 12 weeks from baselineUp until the end of the treatment
measure: Phase Ib: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
timeFrame: Up to 90 days after the last dose of JMT203
measure: Phase Ib: Blood concentration of JMT203;
timeFrame: Up to 90 days after the last dose of JMT203
measure: Phase Ib: PD indicators include β-hydroxybutyric acid.
timeFrame: Up to 24 weeks
measure: Phase Ib: Incidence of ADA.
timeFrame: Up to 90 days after the last dose of JMT203
measure: Phase Ib: overall survival (OS).
timeFrame: Approximately up to 3 years
Other outcomes:
Locations:
city: Zhejiang
country: China
facility: Sir run run shaw Hospital
Study officials:
References: