SMET12 and Toripalimab Combined Chemotherapy in Patients With EGFR Positive Advanced Non-small Cell Lung Cancer (NSCLC)

Early Phase 1

Not yet recruiting

Brief Summary: 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.

Recruitment & Eligibility

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).
3. 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.
2. 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.
3. Fertile individuals unable to maintain effective contraception during the trial.
4. 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.
5. Individuals deemed unsuitable for participation in this clinical trial by the investigator for various reasons .

Arm && Interventions

Group	Intervention	Description
Treatment-naïve subjects with EGFR positive advanced Lung Adenocarcinoma	SMET12	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	SMET12	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	SMET12	toripalimab：3mg/kg， Q2W； SMET12：60μg，Q2W； Docetaxel 60-75 mg/m2 d1Q3W，administered for 2\~4 cycles

Primary Outcome Measures

Name	Time	Method
incidence of adverse events	1 year	Adverse events incidence refers to the frequency of adverse events
rate of adverse events	1 year	All adverse events will also be rated based on the NCI CTCAE version 5.0.
Laboratory aberrations	1 year	Laboratory outliers refer to measurement results that significantly deviate from the normal reference range in laboratory testing.

Secondary Outcome Measures

Name	Time	Method
disease control rate	1 year	Disease control rate: DCR
Progression-free survival	1 year	Progression-free survival (PFS) as assessed by the investigators according to RECIST 1.1 criteria
DOR（ Duration of Response）	1 year	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.

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