This is a single-arm clinical study evaluating the safety, tolerability, and preliminary efficacy of JS212 in combination with JS111 as first-line treatment in participants with epidermal growth factor receptor (EGFR)-mutant locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not received prior systemic therapy for advanced disease.
The study consists of a safety lead-in stage followed by a clinical expansion stage. Approximately 20 participants are planned to be enrolled across the two stages. Participants will receive JS212 by intravenous infusion on Day 1 of each 21-day cycle and JS111 at 160 mg orally once daily until treatment discontinuation criteria are met.
During the safety lead-in stage, up to 10 participants will be enrolled and monitored for significant toxicities during the first 21 days after initial administration. The Safety Monitoring Committee (SMC) will review available safety, tolerability, and efficacy data and determine the JS212 dose to be further evaluated, whether an additional higher or lower dose should be explored, and whether the study may proceed to the clinical expansion stage.
Inclusion Criteria:
Participants must meet all of the following criteria to be eligible for enrollment in this study:
Exclusion Criteria:
Participants meeting any of the following criteria will be excluded from the study:
1. Any of the following disease-related conditions:
2. Receipt of any of the following treatments:
3. Toxicities from prior antitumor therapy that have not recovered to Grade 1 or lower according to CTCAE.
4. Known allergy or hypersensitivity to any study treatment or any of its excipients.
5. Any of the following cardiac findings:
1. Fridericia-corrected QT interval (QTcF) at rest of ≥450 milliseconds in male participants or ≥470 milliseconds in female participants, based on the mean of 3 QTcF measurements obtained during screening; 2. Clinically significant arrhythmia, including but not limited to complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, or PR interval >250 milliseconds; 3. Risk factors for torsades de pointes, such as clinically significant hypokalemia as judged by the investigator, a family history of long QT syndrome, or a family history of arrhythmia, such as pre-excitation syndrome; 4. Left ventricular ejection fraction (LVEF) <50%. 6. Any condition that may affect the absorption, distribution, metabolism, or elimination of oral medication, including inability to swallow medication, frequent vomiting, persistent uncontrolled diarrhea, extensive gastrointestinal resection, Crohn's disease, or ulcerative colitis.
7. Confirmed or suspected interstitial lung disease, drug-induced pneumonitis, a history of idiopathic pneumonitis or idiopathic pulmonary fibrosis, or another moderate or severe pulmonary disease that substantially impairs lung function, except for Grade 1 or lower radiation pneumonitis.
8. Any severe or uncontrolled ocular disorder, particularly severe dry eye syndrome, keratoconjunctivitis sicca, severe exposure keratitis, or another condition that may increase the risk of epithelial injury, as judged by the physician; or an ocular abnormality requiring surgery or expected to require surgery during the study, except for cataracts not requiring urgent surgery.
9. Severe infection of CTCAE Grade 3 or higher within 4 weeks before the first dose of study treatmen.
10. A history of immunodeficiency, including a positive human immunodeficiency virus test, another acquired or congenital immunodeficiency disorder, a history of organ transplantation or allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation.
11. Active tuberculosis infection identified by medical history or computed tomography, a history of active tuberculosis infection within 1 year before enrollment, or a history of active tuberculosis infection more than 1 year before enrollment without adequate standard treatment.
12. Active hepatitis B, defined as hepatitis B surface antigen (HBsAg) positivity with hepatitis B e antibody (HBeAb) or hepatitis B core antibody (HBcAb) positivity and HBV DNA ≥1000 copies/mL or ≥200 IU/mL; or active hepatitis C, defined as hepatitis C virus antibody positivity with HCV RNA above the lower limit of detection of the assay.
13. Any other malignancy diagnosed within 5 years before the first dose that required treatment, except for malignancies with a low risk of metastasis and a 5-year survival rate greater than 90%, such as adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, adequately treated localized prostate cancer, or adequately treated papillary thyroid carcinoma.
14. Female participants who are pregnant, breastfeeding, or planning to become pregnant during the study.
15. Uncontrolled concomitant disease, including but not limited to symptomatic congestive heart failure within 6 months before the first dose of study treatment, uncontrolled hypertension, unstable angina pectoris, uncontrolled arrhythmia.
16. Any other factor that, in the investigator's judgment, may cause the participant to discontinue the study prematurely, including a current or prior medical condition, including psychiatric illness, requiring concomitant treatment; a clinically significant laboratory abnormality; or family or social circumstances that may affect participant safety or the collection of study data.
kui_zhang@junshipharma.com+8618168028925
JS212:JS212 will be administered by intravenous infusion on Day 1 of each 21-day cycle. JS111:160 mg once daily (QD)
503091240@qq.com086 13965082087
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