A Phase 1 Study of JMT108 in Participants With Advanced Solid Tumors

This Phase 1 study is a single agent, 2-part (including dose escalating and expansion) study conducted in patients with locally advanced or metastatic solid tumors who are unresponsive or intolerant to all standard of care or have no standard of care available.

Dose escalation (Phase 1a) - Dose escalation will be conducted using a BOIN design.

In the dose-escalation phase, a total of 4 dose levels-0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, and 2 mg/kg-will be sequentially escalated. The BOIN design is adopted for the dose-escalation part of this study to determine the MTD. The target toxicity rate for the MTD is 0.3, and the maximum sample size for the dose-escalation BOIN design is 30 participants. Participants are enrolled to receive treatment in cohorts of size 3. Dose escalation and de-escalation decisions are made based on the occurrence of DLTs within the DLT observation window.

After thorough evaluation by the SMC, one or more dose levels may be added between the highest escalated dose level and the next lower dose level for better DLT assessment.

The dose escalation phase includes a screening period (D-28 to D-1), a treatment period, an end of treatment (EOT) visit, and a follow-up period.

Cohort expansion (Phase 1b) - Based on the results of Phase 1a, the administration dose and frequency for the cohort expansion phase of study will be determined. If necessary, several different doses/frequencies may be selected for cohort expansion. Participants may be enrolled in the cohort expansion study with tumor types including but not limited to Cohort 1: lung cancer, Cohort 2: colorectal cancer, Cohort 3: liver cancer, Cohort 4: gastric cancer, Cohort 5: melanoma and Cohort 6: other advanced solid tumors (including cervical cancer, renal cancer, bile duct cancer, head and neck squamous cell head and neck cancer, etc.).

Major Inclusion Criteria:

• Age ≥18 years
• Participants with histologically or cytologically confirmed locally advanced or metastatic solid tumors who are unresponsive or intolerant to all standard of care or have no standard of care available
• At least one evaluable tumor lesion according to RECIST v1.1.
• ECOG performance status score ≤2.
• Expected survival ≥ 3 months

Major Exclusion Criteria:

• Active central nervous system metastases and/or leptomeningeal metastases
• AEs from prior therapy which have not recovered to Grade ≤1 or baseline as per NCI CTCAE v5.0

Prior therapy

• Any other unapproved investigational drugs or treatments within 4 weeks prior to the first dose of the investigational drug (C1D1).
• Chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy, or other anti-tumor therapies within 4 weeks prior to the first dose of the investigational drug, except in the following situations:

• Nitrosoureas or mitomycin C within 6 weeks prior to the first dose of the investigational drug;
• Use of oral fluoropyrimidines and small-molecule targeted drugs within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to the first dose of the investigational drug;
• Use of herbal medicine/products with anti-tumor indications within 2 weeks prior to the first dose of the investigational drug.