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

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.

Inclusion Criteria:

Inclusion Criteria:

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

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，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.

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. Adequate organ function, meeting relevant laboratory test standards （without transfusion or hematopoietic growth factor support within 14 days prior to testing）:

6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: ≤1;

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.