A Phase II Study of JS212 in Combination With JS111 in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC)
This is a Phase II study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of JS212 in combination with JS111 in patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR-sensitizing mutations who have progressed after prior EGFR-TKI therapy. The study consists of two parts: a dose-escalation phase followed by an expansion phase. Approximately 30 participants will be enrolled. The dose-escalation phase will explore the safety and tolerability of escalating doses of JS212 in combination with a fixed dose of JS111, using a Bayesian optimal interval (BOIN) design. Based on safety and tolerability data, a recommended Phase III dose (RP3D) will be determined. The expansion phase will further evaluate safety and preliminary anti-tumor activity at the selected dose level.
• Participants must meet all of the following criteria to be eligible for this study:
• Age between 18 and 75 years (inclusive) at the time of signing the informed consent form (ICF), regardless of sex;
• Histologically or cytologically confirmed recurrent or metastatic non-squamous NSCLC that is unresectable and not amenable to curative chemoradiotherapy;
• Confirmed EGFR-sensitizing mutation, including:
• Exon 19 deletion or L858R mutation,Either alone or in combination with other EGFR mutations, Including those with concurrent T790M mutation positivity.Local laboratory reports are acceptable, provided that the test method is well-validated, or has passed external quality assessment (EQA), or is conducted by a certified molecular pathology/genetic testing laboratory, or is approved by NMPA;
• Prior treatment with:
• EGFR-TKIs, and If applicable, ≤1 line of platinum-based doublet chemotherapy, with radiologically confirmed disease progression per RECIST v1.1;
• At least one measurable lesion per RECIST v1.1;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Estimated life expectancy of ≥12 weeks;
• Adequate organ function meeting the following criteria (Note: No blood transfusion or hematopoietic growth factors are allowed within 14 days prior to screening assessments):
∙ Absolute neutrophil count ≥1.5 × 10⁹/L;
‣ Platelet count ≥100 × 10⁹/L;
‣ Hemoglobin ≥90 g/L (≥9 g/dL);
‣ ALT and AST ≤2.5 × ULN (≤5 × ULN in case of liver metastases);
‣ Total bilirubin ≤1.5 × ULN;
‣ Creatinine clearance ≥50 mL/min (calculated by Cockcroft-Gault formula);
‣ Activated partial thromboplastin time (APTT) ≤1.5 × ULN and international normalized ratio (INR) ≤1.5(patients on stable anticoagulant therapy such as low molecular weight heparin or warfarin are allowed if INR is within the therapeutic range);
• Female participants of childbearing potential (WOCBP) who are sexually active with non-sterilized male partners must:
• Have a negative serum pregnancy test within 7 days prior to first dose, and Agree to highly effective contraception and have no plans for pregnancy from signing the ICF until: 7 months after the last dose of JS212, and 2 months after the last dose of JS111, whichever period is longer (definition of WOCBP is provided in Section 10.3);
⁃ Non-sterilized male participants who are sexually active with women of childbearing potential must: Agree to use effective contraception as described in Section 10.3.2 from signing the ICF until 4 months after the last dose of JS212 or JS111, and Refrain from sperm donation during this period;
⁃ Participants must voluntarily participate in this study and provide written informed consent.