- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05164848
JMT101 Combined With Afatinib in Patients With Advanced Esophageal Squamous Cell Carcinoma After Standard Therapy
A Multicenter, Open-label, Phase Ib Study to Evaluate the Safety and Efficacy of JMT101 Combined With Afatinib in Patients With Advanced Esophageal Squamous Cell Carcinoma Who Have Failed Standard Therapy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Lin Shen
- Phone Number: +86-10-88196561
- Email: linshenpku@163.com
Study Locations
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Beijing
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Beijing, Beijing, China
- Recruiting
- Beijing Cancer Hospital
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Contact:
- Lin Shen
- Email: linshenpku@163.com
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Chongqing
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Chongqing, Chongqing, China
- Recruiting
- Chongqing University Cancer Hospital
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Contact:
- Yongsheng Li
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Hefei
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Hefei, Hefei, China
- Recruiting
- Anhui Provincial Hospital
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Contact:
- Dong Qian
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Henan
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Henan, Henan, China
- Recruiting
- Henan Cancer Hospital
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Xingxiang
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Xingxiang, Xingxiang, China
- Recruiting
- Xinxiang Central Hospital of Henan Province
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Contact:
- Chunqing Li
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age of 18 years or above, without gender limitation;
- Histological or cytologically confirmed esophageal squamous cell carcinoma;
- Patients with metastatic disease or locally advanced disease (UICC or AJCC 8th Edition) unsuitable for radical surgery or radiotherapy; with direct invasion of adjacent organs (such as aorta or trachea) (T4b) should be closely assessed for the risk of bleeding before enrollment;
- Patients who have failed first-line or above treatments. The treatment failure is defined as disease progression or intolerable toxicity during or after the last dose of systemic standard chemotherapy, and recurrence or metastasis during treatment or within 6 months of discontinuation of radical therapy including radical concurrent chemoradiotherapy and neoadjuvant/adjuvant therapy (chemotherapy or chemoradiotherapy);
- At least 1 measurable lesion according to RECIST 1.1 at baseline; if there is only one measurable lesion at baseline, the area must have not had prior radiotherapy or there must be evidence of apparent progression after radiotherapy;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
- Life expectancy exceeds 3 months;
The function of major organs and bone marrow meet the following criteria within 7 days before treatment (No blood transfusion, erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), or other support therapy within 7 days prior to administration of the study drug):
Blood routine: absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count ≥80×10^9/L, hemoglobin ≥80 g/L; Kidney function test: Serum creatinine ≤1.5×upper limit of normal (ULN); Liver function tests: total bilirubin ≤1.5×ULN (≤3×ULN for patients with liver metastasis), aspartate aminotransferase ( AST) and alanine aminotransferase (ALT ) ≤3×ULN ( ≤5×ULN for patients with liver metastasis); Blood coagulation: International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN, activated partial thromboplastin time (APTT) ≤ 1.5×ULN.
- The fertile women should have a negative blood pregnancy test within 7 days before enrollment; fertile men or women must agree to use effective contraceptive methods during the whole trial period and six months after the last administration;
- Patients fully understand and voluntarily participate in this study and sign informed consent.
Exclusion Criteria:
- Previously treated with EGFR antibody;
- Patients whose tumor has invaded important blood vessels or is much more likely to invade important blood vessels and cause fatal hemorrhage during the study according to the investigator's judgement; patients who have hemorrhage in the lung or other parts, have a bleeding tendency, or are receiving thrombolytic or anticoagulant therapy;
- Anti-tumor therapy such as chemotherapy, biological therapy, targeted therapy, immunotherapy, etc. within 4 weeks before the first administration of the study drug; oral small molecule targeting drugs within 2 weeks of the first dose or within the 5 half-life of known drugs (whichever is longer); radiotherapy within 2 weeks before the first administration of the study drug;
- Received other investigational product within 4 weeks before the first administration of the study drug;
- Received major organ surgery (excluding needle biopsy) or suffered significant trauma within 4 weeks before the first administration of the study drug;
- Received strong inducers and strong inhibitors of P-gp within 2 weeks before the first administration of the study drug;
- Uncontrolled cancer pain; not at a stable dose of anesthetic analgesics at the time of enrollment.
- Adverse reactions of previous anti-tumor treatments have not yet recovered to ≤ grade 1 according to CTCAE 5.0 (except for the toxicity without safety risk judged by investigator, such as alopecia);
- Central nervous system metastasis or meningeal metastasis;
- History of autoimmune disease or immunodeficiency disease including human immunodeficiency virus antibody (HIV-Ab) positive, or suffering from other acquired or congenital immunodeficiency diseases, or history of organ transplantation;
- Active hepatitis B, active hepatitis C, or positive for treponema pallidum antibodies;
- History of severe cardiovascular disease;
- History of other malignancies within 5 years before the first administration of the study drug, except: malignant lesions that have been treated with therapeutic measures and no known active lesions within 5 or more years before enrolment, and are judged by the treating physician to be at low risk of recurrence; adequately treated non-melanoma skin cancer and cervical cancer in situ without evidence of progression; or prostatic intraepithelial neoplasia without evidence of recurrence of prostate cancer.
- Patients with any severe or uncontrollable disease are unsuitable to participate in this clinical trial according to the investigator's judgement;
- Known hypersensitivity or intolerance to any component of the study drug or its excipients;
- Past or present interstitial pneumonia/pulmonary disease;
- Pregnant or lactating women;
- Other situations that may increase the risks related to the study drug or affect compliance of the trial compliance are not suitable for the trial as determined by the investigator.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort A
JMT101 combined with two dose levels of afatinib will be tested according to the "3 + 3" dose-escalation design.
The dose-limiting toxicity (DLT) will be assessed from the first administration to the end of the first cycle (28 days).
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JMT101 will be administered intravenously at 6 mg/kg every 2 weeks (q2w) in each 28-week cycle.
Afatinib will be administered orally at 30 mg or 40 mg per day (qd) in each 28-week cycle.
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Experimental: Dose Expansion Cohort
Once the safe and effective dose has been determined, an expansion cohort will be recruited to further evaluate the efficacy and safety of the selected dose.
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JMT101 will be administered intravenously at 6 mg/kg every 2 weeks (q2w) in each 28-week cycle.
Afatinib will be administered orally at 30 mg or 40 mg per day (qd) in each 28-week cycle.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Treatment-related Adverse Events,afety and Tolerability
Time Frame: Throughout the study period, with an average of 2 years
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Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
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Throughout the study period, with an average of 2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: Up to approximately 2 years
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Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST).
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Up to approximately 2 years
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Duration of response (DOR)
Time Frame: Up to approximately 2 years
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Measure of time from first response to disease progression or death
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Up to approximately 2 years
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Disease control rate (DCR)
Time Frame: Up to approximately 2 years
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Percentage of patients who achieve partial response (PR) or complete response (CR) or stable disease (SD) based on Response Evaluation Criteria In Solid Tumors (RECIST)
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Up to approximately 2 years
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Progression free survival (PFS)
Time Frame: Up to approximately 2 years
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Measure of time from study treatment to disease progression or death
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Up to approximately 2 years
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Overall survival (OS)
Time Frame: Up to approximately 2 years
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Measure of time from study treatment to patient's death or lost to follow-up
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Up to approximately 2 years
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Pharmacokinetic profile of JMT101 (AUC0-t)
Time Frame: Pre-dose and multiple timepoints up to 30 days after the lase dose
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area under the plasma concentration versus time curve
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Pre-dose and multiple timepoints up to 30 days after the lase dose
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Pharmacokinetic profile of JMT101 (Cmax)
Time Frame: Pre-dose and multiple timepoints up to 30 days after the lase dose
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Peak plasma concentration
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Pre-dose and multiple timepoints up to 30 days after the lase dose
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Pharmacokinetic profile of JMT101 (Tmax)
Time Frame: Pre-dose and multiple timepoints up to 30 days after the lase dose
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Time for peak concentration
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Pre-dose and multiple timepoints up to 30 days after the lase dose
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Pharmacokinetic profile of JMT101 ( t½)
Time Frame: Pre-dose and multiple timepoints up to 30 days after the lase dose
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half life of JMT101
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Pre-dose and multiple timepoints up to 30 days after the lase dose
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The incidence of anti-drug antibody (ADA)
Time Frame: Pre-dose and multiple timepoints up to 30 days after the lase dose
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anti-drug antibody which can result in treatment failure by blocking the pharmacological function of the drug.
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Pre-dose and multiple timepoints up to 30 days after the lase dose
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The incidence of neutralizing antibody (Nab)
Time Frame: Pre-dose and multiple timepoints up to 30 days after the lase dose
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neutralizing anti-drug antibody which can result in treatment failure by blocking the pharmacological function of the drug.
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Pre-dose and multiple timepoints up to 30 days after the lase dose
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The correlation of biomarkers with efficacy
Time Frame: Up to approximately 2 years
|
The biomarkers include PIK3CA, PTEN, KRAS, BRAF, CDH1, EGFR status detected by immunohistochemical (IHC) and fluorescence in-situ hybridization (FISH).
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Up to approximately 2 years
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Neoplasms, Squamous Cell
- Esophageal Neoplasms
- Carcinoma
- Carcinoma, Squamous Cell
- Esophageal Squamous Cell Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Afatinib
Other Study ID Numbers
- JMT101-CSP-004
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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