ILKN421H Plus Pembrolizumab in Advanced Non-Small Cell Lung Cancer

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)

Status

Recruiting

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07452224

Enrollment

Registered

2026-03-05

Start date

2026-06-29

Completion date

2029-10-01

Last updated

2026-07-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Brief summary

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.

Interventions

DRUGILKN421H

Participants will receive ILKN421H in combination with pembrolizumab once every 3 weeks (Q3W). ILKN421H will be administered via i.v. infusion, starting at a rate of 75 mL/h for the first 20 minutes. If no infusion-related reactions are observed, the infusion rate can be increased to 150 mL/h for the remainder of the infusion.

DRUGPembrolizumab

Pembrolizumab will be administered intravenously first. After the infusion ends, at least 4 hours must pass before the intravenous infusion of ILKN421H can begin. Each infusion will last for 1 hour, and the infusion rate will follow the same guidelines

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

To be enrolled in this study, participants must meet all the following inclusion criteria: 1. Provide written informed consent after full understanding of the study. 2. Adults at least 18 years of age. 3. ECOG performance status of 0 or 1. 4. Life expectancy ≥12 weeks. 5. 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. 6. 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. 7. Adequate organ and marrow function within 7 days before first dose, as defined below: 1. Absolute neutrophil count (ANC) ≥1.5×10⁹/L 2. Platelets (PLT) ≥100×10⁹/L 3. Hemoglobin (HGB) ≥90 g/L 4. Alanine aminotransferase (ALT) ≤2.5×ULN (≤5×ULN if known liver involvement) 5. Aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN if known liver involvement) 6. Total bilirubin (TBIL) ≤1.5×ULN (≤3.0×ULN if diagnosed with Gilbert's syndrome) 7. Serum creatinine ≤1.5×ULN or estimated glomerular filtration rate (eGFR, calculated by Cockcroft-Gault formula or 24-hour urine measurement) ≥40 mL/min 8. 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. 8. 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). 9. Willing and able to comply with study schedules and all protocol requirements. 10. 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.

Exclusion criteria

To be included in this study, participants must not meet any of the following

Design outcomes

Primary

Measure	Time frame	Description
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.	Up to 3 years.	Assessing the incidence of adverse events (AEs) using the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0)
To assess the ORR(Objective response rate) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer	up to 3 years	Defined as the proportion of subjects with Confirmed ORR according to iRECIST.

Secondary

Measure	Time frame	Description
To assess the AUC of HSA-IL2v protein(Human serum albumin interleukin 2 fusion protein) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: AUC.
To assess the Cmax of HSA-IL2v protein(Human serum albumin interleukin 2 fusion protein) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Cmax.
To assess the Ctrough of HSA-IL2v protein(Human serum albumin interleukin 2 fusion protein) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Ctrough
To assess the CL of HSA-IL2v protein(Human serum albumin interleukin 2 fusion protein) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: CL
To assess the Vss of HSA-IL2v protein(Human serum albumin interleukin 2 fusion protein) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Vss.
To assess the Tmax of HSA-IL2v protein(Human serum albumin interleukin 2 fusion protein) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Tmax
To assess the T1/2 of HSA-IL2v protein(Human serum albumin interleukin 2 fusion protein) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: T1/2
To assess the AUC of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: AUC.
To assess the Cmax of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage participants. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Cmax.
To assess the Ctrough of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Ctrough
To assess the CL of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: CL.
To assess the Vss of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Vss.
To assess the Tmax of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Tmax.
To assess the T1/2 of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: T1/2
To assess the AUC of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: AUC
To assess the Cmax of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Cmax
To assess the Ctrough of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Ctrough.
To assess the CL of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: CL
To assess the Vss of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Vss.
To assess the Tmax of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Tmax.
To assess the T1/2 of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.	Cycle1，Cycle 3， Cycle5 and Cycle 7 for participants with safety run-in stage， and Cycle 1 Day 2 for participants without safety run-in stage. Each cycle is 21 days.	To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: T1/2.
To assess the DOR in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer	Through study completion, an average of 3 years.	Defined as the time from the first documentation of iCR or iPR until the first documentation of iCPD or death due to any cause, whichever occurs first.
To assess the DCR in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer	Through study completion, an average of 3 years.	Defined as the proportion of participants with a confirmed response of iCR, iPR, or immune Stable Disease (iSD), as assessed by iRECIST.
To assess the PFS in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer	Through study completion, an average of 3 years.	Defined as the time from the first dose of study treatment to the first documentation of iCPD or death due to any cause, whichever occurs first.
To assess the OS in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer	Through study completion, an average of 3 years.	Defined as the time from the first dose of study treatment to death due to any cause.

Countries

United States

Contacts

CONTACTHaining Huang

HHuang@Cytimm.com858-209-6722

STUDY_DIRECTORHaining Huang

iLeukon

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Jul 11, 2026