An Open-Label Phase II Study of ILKN421H in Combination With Pembrolizumab in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
This is a multicenter, open-label, phase II study to evaluate the safety, tolerability, clinical activity, and pharmacokinetics of ILKN421H in combination with pembrolizumab in participants with locally advanced or metastatic NSCLC. The study consists of 4 cohorts in participants with locally advanced or metastatic NSCLC ( squamous \[sq\] or non-squamous \[non-sq\]) without functional genomic alterations including EGFR, ALK and Ros-1, who failed systemic PD-1/L1 inhibitor treatment either alone or in combination with standard chemotherapy (post-IO) (Cohort 1 and 2), or without any prior systemic anti-cancer therapy (1L) with PDL-1 TPS ≥1% (Cohort 3 and 4). Participants will be dosed either with 1.6 mg of ILKN421H (Cohort 1 and Cohort 3) or 2.4 mg of ILKN421H (Cohort 2 and Cohort 4) in combination with 200 mg pembrolizumab. Both treatments will be administered through intravenous (i.v.) infusion every 3 weeks (Q3W) on Day 1 of each cycle with 21-day as one cycle, while ILKN421H will be dosed 4 hours after pembrolizumab. All 4 cohorts will have 3 study periods: * Screening Period: ≤ 28 days prior to first dose of study treatment; * Treatment period: 21-day cycles until unacceptable toxicity, lost to follow-up, disease progression, withdrawal of consent, death, or the sponsor closes the study, whichever occurs first; * Follow-up Period: 30-day safety follow-up and a Long-Term follow-up every 6-month for survival information.
• To be enrolled in this study, participants must meet all the following inclusion criteria:
• Provide written informed consent after full understanding of the study.
• Adults at least 18 years of age.
• ECOG performance status of 0 or 1.
• Life expectancy ≥12 weeks.
• At least one measurable lesion per iRECIST/RECIST 1.1 criteria, defined as:
• Lymph node lesion with short axis ≥1.5 cm or non-lymph node lesion with longest diameter ≥1 cm on CT/MRI; If the only lesion has undergone prior local treatment (radiotherapy, ablation, vascular intervention, etc.), there must be clear imaging evidence of disease progression in this lesion after local treatment.
• Participants must have locally advanced or metastatic NSCLC, confirmed by available pathology records or current biopsy, that is advanced (non-resectable), or recurrent, for which no alternative, curative standard therapy exists. For Cohort 1 and Cohort 2, pathologically or cytologically confirmed advanced malignant locally advanced or metastatic NSCLC participants who have failed standard PD-1/L1 inhibitor alone or in combination with standard chemotherapy treatment regardless of PD-L1 expression. For Cohort 3 and Cohort 4, participants with pathologically or cytologically confirmed advanced, non-resectable locally advanced or metastatic NSCLC, who have previously untreated with any anticancer drugs expressing PD-L1 (TPS≥ 1%) as determined by an FDA-approved test.
• Adequate organ and marrow function within 7 days before first dose, as defined below:
∙ Absolute neutrophil count (ANC) ≥1.5×10⁹/L
‣ Platelets (PLT) ≥100×10⁹/L
‣ Hemoglobin (HGB) ≥90 g/L
‣ Alanine aminotransferase (ALT) ≤2.5×ULN (≤5×ULN if known liver involvement)
‣ Aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN if known liver involvement)
‣ Total bilirubin (TBIL) ≤1.5×ULN (≤3.0×ULN if diagnosed with Gilbert's syndrome)
‣ Serum creatinine ≤1.5×ULN or estimated glomerular filtration rate (eGFR, calculated by Cockcroft-Gault formula or 24-hour urine measurement) ≥40 mL/min
‣ International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5×ULN No component blood transfusion within 14 days prior to the above testing, and no supportive treatments (e.g., G-CSF, TPO, TPO receptor agonists, IL-11, EPO) within 7 days of above testing.
• For Cohort 1 and Cohort 2, prior anti-tumor treatment-related toxicities resolved to ≤ Grade 1 (excluding Grade 2 neurotoxicity, Grade 2 hypothyroidism, any grade alopecia and pigmentation, and Grade 2 AEs that cannot resolve to ≤Grade 1 but remain stable long-term as judged by the investigator based on clinical practice; laboratory parameters refer to Inclusion Criteria 7).
• Willing and able to comply with study schedules and all protocol requirements.
⁃ Women must meet one of the following criteria: postmenopausal for at least 24 consecutive months; surgically incapable of bearing children (i.e., have had a hysterectomy or bilateral oophorectomy); or utilizing a reliable form of contraception (either medication \[oral, implant, or injection\] or a barrier method). In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the participant to use a reliable form of contraceptive during the study Treatment Period and for at least 70 days following the last dose of study drug (Appendix IV). Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product; and Men must agree to the use of contraception during the study Treatment Period and for at least 180 days after the last dose of study drug.