Efficacy and Safety of JMT101 in Patients With Advanced Solid Tumor

Study Overview
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Brief Summary
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This study is a Phase I, open label, multi-center study of to evaluate the safety and efficacy of JMT101 in patients with advanced solid tumor.

Detailed Description
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The objective of the trial is to evaluate the safety and efficacy of JMT101 in patients with advanced solid tumor. This study consists of two parts (Stage I and Stage II). Stage I was a dose escalation study, and Stage II was a dose expansion study.

Official Title
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A Phase I, Open Label, Multi-center Study to Assess the Efficacy and Safety of JMT101 in Patients With Advanced Solid Tumor.

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: JMT101
* Drug: JMT101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Monotherapy: Pathologically or cytologically confirmed, advanced solid tumor, harboring RAS wild type; Combined with chemotherapy: Pathologically or cytologically confirmed, locally advanced /metastatic colorectal cancer, harboring RAS and BRAF V600E wild type. At least 1 measurable lesion according to RECIST 1.1; ECOG score 0 or 1; Stable for more than 14 days of brain metastasis or spinal cord compression. Exclusion Criteria: Receipt of any EGFR inhibitors within 5 months prior to the first dose of study treatment. The second primary malignant tumor was diagnosed within 5 years prior to the first dose of study treatment. Known hypersensitivity to any ingredient of JMT101 or their excipients; Major surgery within prior 4 weeks of first treatment. Receiving an investigational product in another clinical study within 4 weeks; History of serious systemic diseases; Pregnancy or lactating wo

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Cohort<br>Monotherapy: Six dose levels of JMT101 will be tested according to an accelerated titration method followed by a conventional 3 + 3 study design. Combined with chemotherapy: Three dose levels of JMT101 will be tested by a conventional 3 + 3 study design. The dose-limiting toxicity (DLT) will be assessed from the first administration to the end of the first cycle (28 days). | Drug: JMT101<br>* Monotherapy: Accelerated titration method, IV infusion QW; Conventional 3 + 3 study design, IV infusion Q2W. (28-day cycles) Combined with chemotherapy: Conventional 3 + 3 study design, IV infusion Q2W. (28-day cycles)<br>* Other names: FOLFIRI(Irinotecan, Leucovorin Calcium, and Fluorouracil); mFOLFOX6((Oxaliplatin, Leucovorin Calcium, and Fluorouracil);;|
| Experimental: Dose Expansion Cohort<br>Once the effective dose has been determined, an expansion cohort will be opened to evaluate the efficacy and safety of the selected dose. | Drug: JMT101<br>* IV infusion Q2W (28-day cycles)<br>* Other names: FOLFIRI; mFOLFOX6; Irinotecan;;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (defined by the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE V4.03)). |  | From enrollment until 30 days after the last dose | 
| Number of Subjects Experiencing DLTs (Dose Limiting Toxicity). |  | Time from the first dose of study drug up to 4 weeks | 
| Maximum Tolerated Dose (MTD) |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | From first dose to disease progression or end of study, an average of 1 year | 
| Disease control rate (DCR). |  | From first dose to disease progression or end of study, an average of 1 year | 
| Progression free survival (PFS). |  | From first dose to disease progression or end of study, an average of 1 year | 
| Overall survival (OS). |  | From first dose to death or end of study, an average of 1 year | 
| Area under the concentration curve from time 0 to the concentration at last time point (AUC0-last) of JMT101. |  | From enrollment until 30 days after the last dose | 
| Maximum measured plasma concentration (Cmax) of JMT101. |  | From enrollment until 30 days after the last dose | 
| Time to maximum plasma concentration (Tmax) of JMT101. |  | From enrollment until 30 days after the last dose | 
| Half-life (T1/2) of JMT101. |  | From enrollment until 30 days after the last dose | 
| Immunogenicity profile of JMT101. | Blood samples will be collected from subjects post treatment for assessment to detect the presence of anti-drug antibodies(ADA) and neutralizing antibodies by electrochemical luminescence(ECL). | From enrollment until 30 days after the last dose | 
| Potential biomarkers detected in plasma or tumor issue DNA. | The content of RAS(reticular activating system), EGFR(epidermal growth factor receptor), BRAF(B-Raf proto-oncogene) gene will be detected. | From enrollment up to disease progression, an average of 1 year |