NCT06239623
Recruiting
Phase 1
To Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of JSI-1187 Capsule in the Treatment of Advanced Solid Tumors With MAPK Signaling Pathway Mutations
InterventionsJSI-1187
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- JS InnoPharm, LLC
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Adverse Event
Overview
Brief Summary
JSI-1187-101 phase 1 study
Detailed Description
This study is a multicenter, open-label, dose-escalation and dose- expansion phase I clinical study. To investigate the safety, tolerability and PK characteristics of JSI-1187 capsule in Chinese patients with advanced solid tumors harboring MAPK signaling pathway mutations, and to evaluate the efficacy of JSI-1187 capsule in the treatment of advanced solid tumors harboring MAPK signaling pathway mutations.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age of both sexes ranged from 18 to 75 years (inclusive of 18 and 75 years old).
- •For dose escalation phase only:
- •Patients with locally advanced or metastatic solid tumors with histologically or cytologically confirmed MAPK signaling pathway mutations who are unresponsive to standard treatment regimens or for whom no standard treatment regimens are available;
- •Only in the extension stage (all the following conditions must be met):
- •Patients who have histologically or cytologically confirmed, locally advanced or metastatic solid tumors with the following MAPK signaling pathway mutations that do not respond to or have no standard treatment options:
- •Locally advanced or metastatic head and neck cancer, melanoma, small bowel cancer, bile duct cancer, and gallbladder cancer with BRAF non-V600 (G469, L597, L485, etc.) mutation (approximately 10-30 cases, subject number adjusted according to efficacy); Locally advanced or metastatic colorectal cancer, cholangiocarcinoma, gallbladder cancer, small bowel cancer or other solid tumors with BRAF V600 E mutation (approximately 10-20 cases, of which colorectal cancer is expected to be 3-6 cases, the number of subjects will be adjusted according to efficacy); KRAS G12V-mutated, locally advanced or metastatic non-small- cell lung cancer (approximately 10 patients, adjusted for the number of participants according to efficacy).
- •ECOG performance status (Appendix 2) is 0-
- •Life expectancy of ≥12 weeks.
- •patients should have adequate end-organ function, with laboratory results 7 days before the first dose meeting the following requirements: Bone marrow reserve: absolute neutrophil count (ANC) ≥1.5×109/L, platelet ≥100×109/L, and hemoglobin ≥90 g/L;(no use of hematopoietic stimulating factors such as EPO, G-CSF or GM-CSF in the 14 days before the test, and no blood transfusion in the 14 days before the test) Liver function: serum albumin ≥3.0 g/dL; Total bilirubin ≤1.5× upper limit of normal value (ULN), ALT and AST≤ 2×ULN, if liver metastasis or liver cancer patients, ALT or AST≤3×ULN; Renal function: creatinine ≤1.5×ULN or creatinine clearance ≥60 mL per minute (according to the Cockcroft-Gault formula; see Appendix 3); Coagulation function: INR≤1.5×ULN, APTT ≤1.5×ULN.
- •Cardiac function: left ventricular ejection fraction (LVEF)≥50%.
Exclusion Criteria
- •Patients with a history of allergy to any component of JSI-1187 or its pharmaceutical excipients.
- •Patients with prolonged QTcF (QTcF: male \>450 ms, female \>470ms, QTcF formula is shown in Appendix 5).
- •Patients who has previously received other ERK inhibitors.
- •Active central nervous system tumors or central nervous system metastases, as indicated by clinical symptoms, cerebral edema, need for systemic hormone use, and disease progression. Patients with treated tumors or metastases of the central nervous system are eligible if they have been clinically stable (as determined by imaging or other clinical testing) for at least 8 weeks and if they had stopped immune suppressive systemic hormones (\> 10 mg per day of prednisone or equivalent) for at least 4 weeks before the first dose of study drug.
- •Patients with basal-cell, squamous-cell, or carcinoma in situ are excluded if they had a history of other malignancies within 2 years before enrollment, have undergone potentially curative treatment, and have been free of disease recurrence for 5 years after the initiation of treatment.
- •History of or current evidence/risk of retinal vein occlusion or central serous retinopathy.
- •Have received antineoplastic therapy within 28 days before the first dose, including but not limited to: chemotherapy, biotherapy, radiotherapy (except palliative radiotherapy for patients with bone metastases), endocrine therapy, targeted antineoplastic therapy (except nitrosourea and mitomycin C); Received nitrosourea or mitomycin C within 6 weeks before the first dose. Had received treatment with a traditional Chinese medicine with definite antitumor effects within 14 days before the first dose. Except for alopecia and eligibility criteria, radiation-related toxicities (including radiodermatitis dermatitis, post-radiation recall reactive dermatitis, soft tissue fibrosis, etc.) did not recover to grade 1 or lower (according to CTCAE 5.0) after palliative radiotherapy in patients with bone metastases.
- •Patients have received other drugs which are still in clinical trials within 28 days before the first dose.
- •Patients who has undergone major surgical procedures or has active ulcers (which are still present) or wounds that do not fully heal within 28 days before the first dose.
- •Chronic systemic comorbidities (e.g., severe chronic lung, liver, kidney, or heart disease) that cannot be controlled (have received active treatment but is not currently stable or may progress/relapse during the trial).
Arms & Interventions
Experimental
Experimental
ERK inhibitor JSI-1187
Intervention: JSI-1187 (Drug)
Outcomes
Primary Outcomes
Adverse Event
Time Frame: through study completion, an average of 1 year
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.
Serious Adverse Events
Time Frame: through study completion, an average of 1 year
Any untoward medical occurrence that at any dose:results in death、is life-threatening、requires inpatient hospitalization or prolongation of existing hospitalization、results in persistent or significant disability/incapacity,or is a congenital anomaly/birth defect
Secondary Outcomes
- Objective Response Rate(through study completion, an average of 1 year)
Investigators
Study Sites (1)
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