JMT101 Combined With Afatinib in Patients With Advanced Esophageal Squamous Cell Carcinoma After Standard Therapy

NCT ID: NCT05164848

Last Updated: 2021-12-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-25

Study Completion Date

2023-10-31

Brief Summary

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This study is a multi-center, open-label, phase Ib study to evaluate the safety, tolerability and efficacy of JMT101 combined with afatinib in patients with advanced esophageal squamous cell carcinoma who have failed standard treatment.

Detailed Description

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This is a multicenter, open-label, dose-escalated phase Ib study aimed to evaluate the safety, tolerability, and efficacy of JMT101 combined with afatinib in patients with advanced esophageal squamous cell carcinoma who have failed standard treatment. This study consists of two stages: dose-escalation stage and dose expansion stage. The dose-escalation stage will be conducted to determine the maximum tolerated dose (MTD) of JMT101 combined with afatinib in patients with advanced esophageal squamous cell carcinoma based on a 3+3 design. JMT101 will be given by intravenous infusion at 6 mg/kg (q2w) of each 28-week cycle. Afatinib will be sequentially administered at 30 mg and 40 mg (qd) of each 28-week cycle. One dose cohort which is verified to be well-tolerated and safe in dose-escalation stage will be selected for dose-expansion to further explore the safety, pharmacokinetic and efficacy of the study drug.

Conditions

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Esophageal Squamous Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

JMT101

Intervention Type DRUG

JMT101 will be administered intravenously at 6 mg/kg every 2 weeks (q2w) in each 28-week cycle.

Afatinib

Intervention Type DRUG

Afatinib will be administered orally at 30 mg or 40 mg per day (qd) in each 28-week cycle.

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.

Group Type EXPERIMENTAL

JMT101

Intervention Type DRUG

JMT101 will be administered intravenously at 6 mg/kg every 2 weeks (q2w) in each 28-week cycle.

Afatinib

Intervention Type DRUG

Afatinib will be administered orally at 30 mg or 40 mg per day (qd) in each 28-week cycle.

Interventions

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JMT101

JMT101 will be administered intravenously at 6 mg/kg every 2 weeks (q2w) in each 28-week cycle.

Intervention Type DRUG

Afatinib

Afatinib will be administered orally at 30 mg or 40 mg per day (qd) in each 28-week cycle.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age of 18 years or above, without gender limitation;
2. Histological or cytologically confirmed esophageal squamous cell carcinoma;
3. 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;
4. 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);
5. 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;
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
7. Life expectancy exceeds 3 months;
8. 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.
9. 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;
10. Patients fully understand and voluntarily participate in this study and sign informed consent.

Exclusion Criteria

1. Previously treated with EGFR antibody;
2. 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;
3. 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;
4. Received other investigational product within 4 weeks before the first administration of the study drug;
5. Received major organ surgery (excluding needle biopsy) or suffered significant trauma within 4 weeks before the first administration of the study drug;
6. Received strong inducers and strong inhibitors of P-gp within 2 weeks before the first administration of the study drug;
7. Uncontrolled cancer pain; not at a stable dose of anesthetic analgesics at the time of enrollment.
8. 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);
9. Central nervous system metastasis or meningeal metastasis;
10. 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;
11. Active hepatitis B, active hepatitis C, or positive for treponema pallidum antibodies;
12. History of severe cardiovascular disease;
13. 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.
14. Patients with any severe or uncontrollable disease are unsuitable to participate in this clinical trial according to the investigator's judgement;
15. Known hypersensitivity or intolerance to any component of the study drug or its excipients;
16. Past or present interstitial pneumonia/pulmonary disease;
17. Pregnant or lactating women;
18. 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking University

OTHER

Sponsor Role lead

Responsible Party

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Shen Lin

Clinical Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

Site Status RECRUITING

Anhui Provincial Hospital

Hefei, Hefei, China

Site Status RECRUITING

Henan Cancer Hospital

Henan, Henan, China

Site Status RECRUITING

Xinxiang Central Hospital of Henan Province

Xingxiang, Xingxiang, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Lin Shen

Role: CONTACT

Phone: +86-10-88196561

Email: [email protected]

Facility Contacts

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Lin Shen

Role: primary

Yongsheng Li

Role: primary

Dong Qian

Role: primary

Suxia Luo

Role: primary

Chunqing Li

Role: primary

Other Identifiers

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JMT101-CSP-004

Identifier Type: -

Identifier Source: org_study_id