Overview
Evaluate the safety and tolerability of JMBI-001 in adults with MYC-positive advanced cancers.
Description
The purpose of this clinical trial is to investigate JMBI-001 for the treatment of MYC-positive advanced tumors and to evaluate its safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and antitumor efficacy.
The main questions this study aims to answer are:
- To evaluate the safety, tolerability, PK, and preliminary antitumor activity of JMBI-001, and to determine the recommended dose for expansion (RDE) and the recommended Phase II dose (RP2D).
- To evaluate the antitumor efficacy, safety, tolerability, and PK of JMBI-001 at the RP2D in selected tumor types.
Participants will:
- Take JMBI-001 orally once daily on an empty stomach for 4 consecutive days, followed by 3 days without treatment. Three such 7-day dosing periods will constitute one 21-day treatment cycle.
- Visit the study site as scheduled to undergo protocol-specified procedures, including medical interviews, physical examinations, blood tests, electrocardiograms, and imaging examinations.
- Continue treatment until a protocol-defined event requiring discontinuation of study treatment or withdrawal from the study occurs.
Eligibility
Inclusion Criteria:
- Able to fully understand the study requirements, voluntarily agree to participate in the study, and provide written informed consent.
- Male or female participants aged 18 to 75 years, inclusive.
- Histologically or cytologically confirmed malignant tumor. Participants with solid tumors must have unresectable locally advanced or metastatic disease for which standard treatment has failed, is not tolerated, or is unavailable. Participants with non-Hodgkin lymphoma must have received at least two prior lines of therapy. Tumor-specific requirements for each study phase are as follows:
- Phase Ia dose-escalation stage: Solid tumors, including but not limited to gastric cancer, colorectal cancer, non-small cell lung cancer, hepatocellular carcinoma, and triple-negative breast cancer. Non-Hodgkin lymphoma, including but not limited to diffuse large B-cell lymphoma and Burkitt lymphoma.
- Phase Ib dose-expansion stage: tumor indications within prespecified tumor types of particular interest, potentially sensitive tumor types or subtypes identified during Phase Ia, or both. Prespecified tumor types of particular interest include, but are not limited to, gastric cancer, colorectal cancer, non-small cell lung cancer, hepatocellular carcinoma, and non-Hodgkin lymphoma.
- Phase II indication-expansion stage: selected tumor indications that meet the prespecified transition criteria during Phase Ib.
- Except for participants enrolled in the accelerated titration stage of Phase Ia, tumor tissue obtained or submitted during screening must be tested by immunohistochemistry and meet the following criteria for MYC positivity:
- Solid tumors: MYC-positive tumor cell nuclei in at least 10% of tumor cells.
- Non-Hodgkin lymphoma: MYC-positive tumor cell nuclei in at least 40% of tumor cells.
- At least one lesion suitable for efficacy assessment, as follows:
- For participants with solid tumors, at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). The longest diameter must be at least 10 mm on spiral computed tomography, or the short-axis diameter of an enlarged lymph node must be at least 15 mm. A lesion selected as a target lesion must not have received radiotherapy within 4 weeks before the first dose of JMBI-001; palliative local radiotherapy to a non-target lesion is permitted.
- For participants with non-Hodgkin lymphoma, according to the Lugano 2014 criteria, the longest diameter must be greater than 1.5 cm for a nodal lesion or greater than 1.0 cm for an extranodal lesion.
Exclusion Criteria:
- Difficulty swallowing or inability to swallow tablets.
- Known hypersensitivity to any component of JMBI-001 tablets.
- Carcinomatous meningitis, brainstem metastasis, or spinal cord compression confirmed by imaging or clinical diagnosis.
- History of a severe neurologic disorder or severe psychiatric or psychological disorder that may interfere with the participant's ability to understand or comply with the study protocol.
- Systemic glucocorticoid therapy within 2 weeks before the first dose of JMBI-001 at a prednisone-equivalent dose greater than 10 mg/day.
- Gastrointestinal disease or abnormality that may affect the absorption of JMBI-001, including but not limited to celiac disease, short bowel syndrome, Crohn disease, ulcerative colitis, gastrointestinal perforation, or severe vomiting or diarrhea.
Other Inclusion/exclusion criteria may apply.
