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

NCT05164848 | Unknown Phase 1

• 1 other identifier: JMT101-CSP-004
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Esophageal Squamous Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-related Adverse Events，afety and Tolerability

  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Throughout the study period, with an average of 2 years

Secondary Outcomes (11)

• Objective Response Rate (ORR)

  Up to approximately 2 years

• Duration of response (DOR)

  Up to approximately 2 years

• Disease control rate (DCR)

  Up to approximately 2 years

• Progression free survival (PFS)

  Up to approximately 2 years

• Overall survival (OS)

  Up to approximately 2 years

Other Outcomes (1)

• The correlation of biomarkers with efficacy

  Up to approximately 2 years

Study Arms (2)

Cohort A

EXPERIMENTAL

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).

Drug: JMT101; Drug: Afatinib

Dose Expansion Cohort

EXPERIMENTAL

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.

Drug: JMT101; Drug: Afatinib

Interventions

JMT101 DRUG

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

Cohort A; Dose Expansion Cohort

Afatinib DRUG

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

Cohort A; Dose Expansion Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Peking University: lead

Study Sites (5)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

RECRUITING

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

RECRUITING

Anhui Provincial Hospital

Hefei, Hefei, China

RECRUITING

Henan Cancer Hospital

Henan, Henan, China

RECRUITING

Xinxiang Central Hospital of Henan Province

Xingxiang, Xingxiang, China

RECRUITING

MeSH Terms

Interventions

Afatinib

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Lin Shen

CONTACT

+86-10-88196561; linshenpku@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: December 21, 2021
• Study Start: December 25, 2021
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: December 21, 2021

Record last verified: 2021-12

Locations

CN (5)