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Esophageal Squamous Cell Carcinoma

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Afatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

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Tyrosine

Afatinib is orally administered at 40mg Qd of each 21 day cycle.

Toripalimab is given by intravenous infusion at 200mg d1 of each 21 day cycle.

Toripalimab

Lin Shen, Professor

Zhihao Lu, Professor

This is a phase 2 trial investigating the effect and safety of afatinib plus toripalimab in previously treated recurrent or metastasic esophageal squamous cell carcinoma with EGFR overexpression or EGFR amplification.

Afatinib Plus Toripalimab in Previously Treated ESCC With EGFR Overexpression or EGFR Amplification

Phase 2 Study of Afatinib Plus Toripalimab in Previously Treated Recurrent or Metastasic Esophageal Squamous Cell Carcinoma With EGFR Overexpression or EGFR Amplification

Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST).

Measure of time from first response to disease progression or death

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).

Measure of time from study treatment to disease progression or death.

Measure of time from study treatment to patient's death or lost to follow-up.

Peking University

Clinical Professor

Enrolled patients in this arm will be administered TGFβR-KO CAR-EGFR T Cells in 3+3 based escalation manner.

Enrolled patients will be administered TGFβR-KO CAR-EGFR T Cells in 3+3 based escalation manner. The infused CAR+ T cell dose in phase IA will be started initially at 1-2×10\^5/kg, dose 2 will be 1×10\^6/kg，and dose 3 will be 1×10\^7/kg, if DLT occurs in dose level 3, the following dose will return to 5×10\^6/kg. In expansion period, the dose of infused CAR+ T cells will be determined by the recommended cell dose from phase IA.

TGFβR-KO CAR-EGFR T Cells

Weidong Han, PhD

Kaichao Feng, MD

Weidong Han, Prof.

kaichao Feng, Ph.D

Chimeric antigen receptor modified T (CART) cell therapy has been identified as a breakthrough therapy in hematologic malignancies. However, CART cell therapy yielded no satisfactory efficacy data in the study of solid tumors. One of major challenges is the complicated immunosuppressive tumor microenvironment (TME) in solid tumors. It has been reported that transforming growth factor-β (TGF-β) is one of the major regulatory factors in the TME. In this study, we construct CAR-EGFR-TGFβR-KO T cell by knocking out TGF-β receptor Ⅱ through CRISPR/Cas9 in order to study the anti-tumor activities and safety profiles of CAR-EGFR-TGFβR-KO T cell in previously treated advanced EGFR positive solid tumors.

Chimeric antigen receptor modified T (CART) cell therapy has been identified as a breakthrough therapy in hematologic malignancies. Different from the promising efficacy in leukemia, lymphoma and multiple myeloma, however, CART cell therapy yielded no satisfactory efficacy data in the study of solid tumors. One of major challenges is the complicated immunosuppressive tumor microenvironment (TME) in solid tumors. It has been reported that transforming growth factor-β (TGF-β) is one of the major regulatory factors in the TME, which plays a key role in promoting tumor initiation, metastasis, and suppressing anti-tumor immunity. In this phase Ⅰstudy, we plan to construct CAR-EGFR-TGFβR-KO T cell by knocking out TGF-β receptor Ⅱ through CRISPR/Cas9 in order to study the anti-tumor activities and safety profiles of CAR-EGFR-TGFβR-KO T cell in the treatment of previously treated advanced EGFR antigen overexpressing solid tumors.

TGFβR-KO CAR-EGFR T Cells will be administered to eligible patients in a 3+3 dose escalation manner.

TGFβR-KO CAR-EGFR T Cells in Previously Treated Advanced EGFR-positive Solid Tumors

Phase Ⅰ Study of EGFR Targeted TGFβR-KO CAR T Cells in the Treatment of Previously Treated Advanced EGFR-positive Solid Tumors

Determining the safety profile following the initiation of treatment and grading these toxicities by CTCAE v5.0

Overall response rate is defined as the sum of partial responses and complete responses

Progression free survival (PFS) is defined as the time from enrollment to documented disease progression or death. Progression will be defined clinically or on imaging as per immune related response evaluation criteria in solid tumors (irRECIST) definition.

Chinese PLA General Hospital

Director of Bio-therapeutic Department

Afatinib is orally administered at 40mg Qd of each 28 day cycle.

This is a phase 2 trial investigating the effect and safety of afatinib in previously treated recurrent or metastasic esophageal squamous cell carcinoma with EGFR overexpression or EGFR amplification.

Afatinib in Previously Treated ESCC With EGFR Overexpression or EGFR Amplification (ESCC-A01)

Phase 2 Study of Afatinib in Previously Treated Recurrent or Metastasic Esophageal Squamous Cell Carcinoma With EGFR Overexpression or EGFR Amplification (ESCC-A01)

Number of adverse events of afatinib in patients with ESCC.

Measure of time from study treatment to disease progression or death

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Afatinib Plus Toripalimab in Previously Treated ESCC With EGFR Overexpression or EGFR Amplification	NCT04880811	Esophageal Squa...	Afatinib Toripalimab	18 Years - 70 Years	Peking University
TGFβR-KO CAR-EGFR T Cells in Previously Treated Advanced EGFR-positive Solid Tumors	NCT04976218	Solid Tumor, Ad... EGFR Overexpres...	TGFβR-KO CAR-EG...	18 Years - 75 Years	Chinese PLA General Hospital
Afatinib in Previously Treated ESCC With EGFR Overexpression or EGFR Amplification (ESCC-A01)	NCT03940976	Esophageal Squa...	Afatinib	18 Years - 70 Years	Peking University

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