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This is a single-arm, sequential study assessing the efficacy and safety of SMET12 and Toripalimab combined chemotherapy in patients with EGFR positive advanced non-small cell lung cancer (NSCLC) : first-line treatment or failed from first-line immune checkpoint inhibitor treatment.The primary objective is to evaluate the anti-tumor activity and safety of SMET12 and Toripalimab combined chemotherapy in patients with EGFR positive advanced NSCLC.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment-naïve subjects with EGFR positive advanced Lung Adenocarcinoma | Experimental | toripalimab:3mg/kg, Q2W; SMET12:60μg,Q2W; Pemetrexed Disodium 500mg/m2 d+Carboplatin AUV=5 d1 Q3W,administered for 2~4 cycles |
|
| Treatment-naïve subjects with EGFR positive advanced Lung Squamous Cell Carcinoma | Experimental | toripalimab:3mg/kg, Q2W; SMET12:60μg,Q2W; paclitaxel 100mg/m2 d1,d8,d15+cisplatin 75mg/m2 d1 Q3W, administered for 2~4 cycles |
|
| Subjects resistant to first-line treatment contain immune checkpoint inhibitors | Experimental | toripalimab:3mg/kg, Q2W; SMET12:60μg,Q2W; Docetaxel 60-75 mg/m2 d1Q3W,administered for 2~4 cycles |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SMET12 | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| incidence of adverse events | Adverse events incidence refers to the frequency of adverse events | 1 year |
| rate of adverse events | All adverse events will also be rated based on the NCI CTCAE version 5.0. | 1 year |
| Laboratory aberrations | Laboratory outliers refer to measurement results that significantly deviate from the normal reference range in laboratory testing. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| disease control rate | Disease control rate: DCR | 1 year |
| Progression-free survival | Progression-free survival (PFS) as assessed by the investigators according to RECIST 1.1 criteria |
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Inclusion Criteria:
1. Has fully understood and voluntarily signed an informed consent form for this study , willing and able to comply with study procedures.
2. Age ≥ 18 years. 3. Histologically confirmed EGFR positive (immunohistochemistry ≥ [+]) advanced NSCLC ,including: (1) Cohort A: Treatment-naïve subjects; (2) Cohort B: Subjects resistant to first-line treatment contain immune checkpoint inhibitors (stability period > 3 months).
4. At least one measurable lesion via RECIST v1.1 criteria 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 6. Expected survival ≥ 3 months. 7. Adequate organ function .
Exclusion Criteria:
1. Driver gene-positive (EGFR, ALK, ROS1) . 2. history of dual primary malignancies within the past 5 years. 3. active autoimmune diseases or a history of autoimmune disorders requiring systemic corticosteroid therapy.
4. systemic infections requiring systemic treatment. 5. known central nervous system metastases or other central nervous system diseases or abnormalities deemed unsuitable for inclusion in this study by the investigator.
6. Fertile individuals unable to maintain effective contraception during the trial.
7. Subjects in Cohort B who have received prior docetaxel treatment. 8. Subjects in Cohort B who experienced Grade 3 or higher immune-related adverse events during first-line treatment with immune checkpoint inhibitors.
9. Individuals deemed unsuitable for participation in this clinical trial by the investigator for various reasons .
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhiyong He | Contact | +86 138 0508 6391 | heyong1015@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fujian Cancer Hospital | Fuzhou | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41583476 | Derived | Lin J, Chen S, Li M, Weng L, Xu H, Wang Q, Zhang J, Lin D, Wang H, Liu Q, He Z. Efficacy and safety of SMET12 in combination with toripalimab and chemotherapy in advanced non-small-cell lung cancer patients tested positive for EGFR protein who are treatment-naive or harbor acquired resistance to standard therapy: a phase 2, multi-cohort clinical trial. Front Immunol. 2026 Jan 8;16:1706961. doi: 10.3389/fimmu.2025.1706961. eCollection 2025. |
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| ID | Term |
|---|---|
| C000656314 | toripalimab |
| D000068437 | Pemetrexed |
| D016190 | Carboplatin |
| D017239 | Paclitaxel |
| D002945 | Cisplatin |
| D000077143 | Docetaxel |
| ID | Term |
|---|---|
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 |
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|
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| SMET12 | Drug |
|
|
|
| SMET12 | Drug |
|
|
|
| 1 year |
| DOR( Duration of Response) | Duration of response (DoR) is defined as the time from first confirmed response (complete response or partial response) to the date of the initial objectively documented tumor progression as determined per investigator assessment using RECIST 1.1 criteria or death due to any cause, whichever occurs first. | 1 year |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000600 | Amino Acids, Dicarboxylic |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |