Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)Phase 2NCT07452224
ILKN421H Plus Pembrolizumab in Advanced Non-Small Cell Lung Cancer
A Phase 2 study testing ILKN421H and Pembrolizumab in people with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC), run by iLeukon Therapeutics, Inc. at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
- What is being tested?
- ILKN421H and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 2 sitesUnited States
- Study dates
- 29 Jun 2026to Oct 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- To be included in this study, participants must not meet any of the following exclusion criteria:
- Known allergy to any component of the investigational drug formulation or IL-2.
- Participation in any therapeutic clinical study and receiving treatment within 28 days prior to the first dose, excluding observational studies or survival follow-up stages of interventional studies.
- Use of immunomodulatory drugs within 14 days or 5 half-life (whichever is longer) before the first dose, including but not limited to thymosin, IL-2, IL-15, interferon, etc.
- Received chimeric antigen receptor T-cell (CAR-T) immunotherapy within 3 months prior to the first dose; chemotherapy (≥6 weeks for nitrosoureas and mitomycin C, ≥14 days for oral fluoropyrimidines), endocrine therapy, targeted therapy (with a washout period of 14 days or 5 half-lives, whichever is longer), immunotherapy (see exclusion criterion 3 for immunomodulatory drugs), tumor embolization, etc., within 28 days prior to the first dose; radiotherapy within 14 days before the first dose, except for palliative radiotherapy, which must be completed at least 7 days prior to the first dose; Exceptions may be allowed if, based on investigator assessment, the subject is still eligible for enrollment.
- Major surgery within 28 days prior to the first dose or minor surgery within 7 days prior to the first dose, or having unhealed wounds, ulcers, or fractures, or requiring elective surgery during the study (except for diagnostic biopsy or insertion of vascular access devices).
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- Vaccination with live attenuated vaccines within 28 days prior to the first dose or planned during the study.
- Use of systemic immunosuppressive agents within 28 days prior to the first dose, except for:
- Intranasal or localized corticosteroids (e.g., intra-articular injection);
- Systemic corticosteroids ≤ 10 mg/day prednisone or equivalent dose;
- Corticosteroids for preventing allergic reactions (e.g., pre-chemotherapy);
- Corticosteroids for preventing infusion reactions;
- Known or confirmed central nervous system (CNS) metastases or carcinomatous meningitis during screening.
- Uncontrolled third-space fluid accumulation requiring repeated drainage, such as pleural effusion, ascites, pericardial effusion, etc. (participants without the need for drainage or who have not had significant accumulation after ceasing drainage for 3 days can be included), or blood-tinged third-space fluid confirmed by diagnostic aspiration.
- History of any other malignant tumors within 5 years prior to the first dose, except for cured early-stage malignancies (e.g., carcinoma in situ or stage I tumors), such as adequately treated basal or squamous cell carcinoma of the skin, surgically resected carcinoma in situ of the cervix or breast, early-stage papillary thyroid carcinoma, or prostate cancer with a Gleason score ≤ 6.
- Active autoimmune diseases or inflammatory diseases [including inflammatory bowel disease (e.g., ulcerative colitis or Crohn's disease), diverticulitis (excluding diverticular disease), celiac disease, systemic lupus erythematosus, sarcoidosis, Wegener's granulomatosis, Graves' disease, rheumatoid arthritis, pituitary inflammation, uveitis, etc.], or a history of such diseases within the past 2 years (participants with conditions such as vitiligo, psoriasis, alopecia, or controlled hypothyroidism or type 1 diabetes requiring only thyroid hormone replacement or insulin therapy are allowed).
- Active or uncontrolled HBV (HBsAg positive and/or HBcAb positive with positive HBV DNA), HCV (HCV-Ab positive with positive HCV RNA), or HIV positive.
- Active bacterial, viral, or fungal infection within 72 hours prior to the first dose (defined by persistent signs/symptoms of infection despite appropriate treatment) or requiring intravenous (i.v.) antibiotics therapy.
- Severe or uncontrolled cardiovascular or cerebrovascular diseases requiring treatment, including but not limited to:
- New York Heart Association (NYHA) Class > 2 heart failure (Appendix II);
- Unstable angina uncontrolled by medication;
- Myocardial infarction within 6 months prior to the first dose;
- History of myocarditis;
- Pericardial tamponade;
- Uncontrolled arrhythmia (e.g., ventricular tachycardia during antiarrhythmic treatment-participants with grade I atrioventricular block or asymptomatic left bundle branch block/right bundle branch block are not excluded);
- QTcF > 470 msec on 12-lead ECG;
- Left ventricular ejection fraction (LVEF) < 50%;
- Uncontrolled hypertension (defined as blood pressure not at targeted level despite ≥1 month of treatment with at least two reasonable and tolerated antihypertensive medications following lifestyle modifications, or blood pressure that can only be effectively controlled with four or more antihypertensive medications) or hypotension;
- Stroke, cerebrovascular accident, or transient ischemic attack within 6 months prior to the first dose.
- Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of the predicted normal value. Suspected COPD participants must undergo FEV1 testing; those with FEV1 < 50% predicted normal value must be excluded.
- Known moderate or severe persistent asthma, a history of asthma within the past 2 years, or currently uncontrolled asthma (note: participants with intermittent asthma or mild persistent asthma under control are eligible).
- History of interstitial lung disease (including drug-induced), pneumoconiosis, pulmonary fibrosis, or severe pulmonary dysfunction; active tuberculosis, currently receiving anti-tuberculosis treatment, or having received anti-tuberculosis treatment within the past year.
- Significant clinical bleeding symptoms within 3 months before the first dose, including hemoptysis of any significant amount (≥ 2.5 mL per episode) within 28 days prior to the first dose.
- History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to the first dose.
- History of deep vein thrombosis, pulmonary embolism, or other severe thromboembolic events within 3 months prior to the first dose (excluding thrombosis caused by vascular access devices or superficial venous thrombosis).
- Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Class B or worse cirrhosis.
- Known history of primary immunodeficiency.
- Known history of organ transplantation or allogeneic hematopoietic stem cell transplantation (corneal transplantation excluded).
- Pregnant or breastfeeding women.
- Any active severe psychiatric disorder, medical disease, or other condition that may interfere with treatment, compliance, or the ability to provide informed consent, as determined by the investigator.
- A history of allergy to pembrolizumab.
- A history of permanent discontinuation of pembrolizumab or similar drugs due to drug-related adverse events (AEs).
- Potential participants may be excluded if, in the judgment of the Principal Investigator (PI), their participation would pose an unacceptable risk to their safety or significantly compromise the integrity or interpretability of the study's efficacy endpoints.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Start Ccbd, Llc
Fort Worth, Texas, 76104
- Recruiting
Valkyrie Clinical Trials, Inc
Los Angeles, California, 90067
About this study
Official title: 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.
- Being tested
- ILKN421H, Pembrolizumab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ILKN421HDrug
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.
PembrolizumabDrug
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 group | Role | What they receive |
|---|---|---|
| 1.6 mg ILKN421H + 200 mg pembrolizumab,2L/2L+ Post-IO NSCLC with all PD-L1 level | Experimental | 1.6 mg of ILKN421H in combination of 200 mg pembrolizumab with i.v. infusion Q3W in participants with 2L/2L+, post-IO NSCLC regardless of PD-L1 level Receives: Drug: ILKN421H; Drug: Pembrolizumab |
| 2.4 mg ILKN421H + 200 mg pembrolizumab,2L/2L+ Post-IO NSCLC with all PD-L1 level | Experimental | 2.4 mg of ILKN421H in combination of 200 mg pembrolizumab with i.v. infusion Q3W in participants with 2L/2L+, post-IO NSCLC regardless of PD-L1 level Receives: Drug: ILKN421H; Drug: Pembrolizumab |
| 1.6 mg ILKN421H + 200 mg pembrolizumab,1L NSCLC with PD-L1 TPS ≥1% | Experimental | 1.6 mg of ILKN421H in combination with 200 mg pembrolizumab in 1L NSCLC with PD-L1 TPS ≥1% Receives: Drug: ILKN421H; Drug: Pembrolizumab |
| 2.4 mg ILKN421H + 200 mg pembrolizumab,1L NSCLC with PD-L1 TPS ≥1% | Experimental | 2.4 mg of ILKN421H in combination with 200 mg pembrolizumab in 1L NSCLC with PD-L1 TPS ≥1% Receives: Drug: ILKN421H; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
Assessing the incidence of adverse events (AEs) using the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0)
Measured: Up to 3 years.
To assess the ORR(Objective response rate) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Defined as the proportion of subjects with Confirmed ORR according to iRECIST.
Measured: up to 3 years
Secondary outcomes (25)
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.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: AUC.
Measured: 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 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.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Cmax.
Measured: 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 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.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Ctrough
Measured: 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 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.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: CL
Measured: 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 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.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Vss.
Measured: 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 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.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Tmax
Measured: 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 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.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: T1/2
Measured: 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 AUC of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: AUC.
Measured: 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 Cmax of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Cmax.
Measured: 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 Ctrough of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Ctrough
Measured: 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 CL of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: CL.
Measured: 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 Vss of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Vss.
Measured: 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 Tmax of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Tmax.
Measured: 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 T1/2 of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: T1/2
Measured: 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 AUC of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: AUC
Measured: 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 Cmax of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Cmax
Measured: 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 Ctrough of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Ctrough.
Measured: 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 CL of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: CL
Measured: 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 Vss of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Vss.
Measured: 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 Tmax of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: Tmax.
Measured: 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 T1/2 of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
To assess the PK of HSA-IL2v protein by collecting serum at protocol-specified time points: T1/2.
Measured: 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 DOR in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer
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.
Measured: Through study completion, an average of 3 years.
To assess the DCR in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Defined as the proportion of participants with a confirmed response of iCR, iPR, or immune Stable Disease (iSD), as assessed by iRECIST.
Measured: Through study completion, an average of 3 years.
To assess the PFS in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer
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.
Measured: Through study completion, an average of 3 years.
To assess the OS in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Defined as the time from the first dose of study treatment to death due to any cause.
Measured: Through study completion, an average of 3 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2026
- Study start29 Jun 2026
- Primary completionJun 2029 (estimated)
- Study completionOct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- iLeukon Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Haining Huang, Study director, iLeukon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07452224
- Sponsor's protocol ID
- IL2V-AST-201US
- Status last verified
- Jul 2026
- First submitted
- 28 Feb 2026
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT07452224
- Acronym / sponsor ID
- IL2V-AST-201US
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- iLeukon Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 29 Jun 2026 (actual)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Oct 2029 (estimated)
- First posted
- 5 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1.6 mg ILKN421H + 200 mg pembrolizumab,2L/2L+ Post-IO NSCLC with all PD-L1 level | Experimental | Drug: ILKN421H, Drug: Pembrolizumab1.6 mg of ILKN421H in combination of 200 mg pembrolizumab with i.v. infusion Q3W in participants with 2L/2L+, post-IO NSCLC regardless of PD-L1 level |
| 2.4 mg ILKN421H + 200 mg pembrolizumab,2L/2L+ Post-IO NSCLC with all PD-L1 level | Experimental | Drug: ILKN421H, Drug: Pembrolizumab2.4 mg of ILKN421H in combination of 200 mg pembrolizumab with i.v. infusion Q3W in participants with 2L/2L+, post-IO NSCLC regardless of PD-L1 level |
| 1.6 mg ILKN421H + 200 mg pembrolizumab,1L NSCLC with PD-L1 TPS ≥1% | Experimental | Drug: ILKN421H, Drug: Pembrolizumab1.6 mg of ILKN421H in combination with 200 mg pembrolizumab in 1L NSCLC with PD-L1 TPS ≥1% |
| 2.4 mg ILKN421H + 200 mg pembrolizumab,1L NSCLC with PD-L1 TPS ≥1% | Experimental | Drug: ILKN421H, Drug: Pembrolizumab2.4 mg of ILKN421H in combination with 200 mg pembrolizumab in 1L NSCLC with PD-L1 TPS ≥1% |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (43 listed)
- To be included in this study, participants must not meet any of the following exclusion criteria:
- Known allergy to any component of the investigational drug formulation or IL-2.
- Participation in any therapeutic clinical study and receiving treatment within 28 days prior to the first dose, excluding observational studies or survival follow-up stages of interventional studies.
- Use of immunomodulatory drugs within 14 days or 5 half-life (whichever is longer) before the first dose, including but not limited to thymosin, IL-2, IL-15, interferon, etc.
- Received chimeric antigen receptor T-cell (CAR-T) immunotherapy within 3 months prior to the first dose; chemotherapy (≥6 weeks for nitrosoureas and mitomycin C, ≥14 days for oral fluoropyrimidines), endocrine therapy, targeted therapy (with a washout period of 14 days or 5 half-lives, whichever is longer), immunotherapy (see exclusion criterion 3 for immunomodulatory drugs), tumor embolization, etc., within 28 days prior to the first dose; radiotherapy within 14 days before the first dose, except for palliative radiotherapy, which must be completed at least 7 days prior to the first dose; Exceptions may be allowed if, based on investigator assessment, the subject is still eligible for enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ILKN421HParticipants 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. | Drug | 1.6 mg ILKN421H + 200 mg pembrolizumab,1L NSCLC with PD-L1 TPS ≥1%, 1.6 mg ILKN421H + 200 mg pembrolizumab,2L/2L+ Post-IO NSCLC with all PD-L1 level, 2.4 mg ILKN421H + 200 mg pembrolizumab,1L NSCLC with PD-L1 TPS ≥1%, 2.4 mg ILKN421H + 200 mg pembrolizumab,2L/2L+ Post-IO NSCLC with all PD-L1 level |
| PembrolizumabPembrolizumab 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 | Drug | 1.6 mg ILKN421H + 200 mg pembrolizumab,1L NSCLC with PD-L1 TPS ≥1%, 1.6 mg ILKN421H + 200 mg pembrolizumab,2L/2L+ Post-IO NSCLC with all PD-L1 level, 2.4 mg ILKN421H + 200 mg pembrolizumab,1L NSCLC with PD-L1 TPS ≥1%, 2.4 mg ILKN421H + 200 mg pembrolizumab,2L/2L+ Post-IO NSCLC with all PD-L1 level |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
Time frame: 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
Time frame: up to 3 years
Defined as the proportion of subjects with Confirmed ORR according to iRECIST.
25 secondary outcomes
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.
Time frame: 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 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.
Time frame: 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 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.
Time frame: 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 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.
Time frame: 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 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.
Time frame: 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 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.
Time frame: 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 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.
Time frame: 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 AUC of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 Cmax of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 Ctrough of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 CL of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Time frame: 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 Vss of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 Tmax of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 T1/2 of mRNA(messenger-ribonucleic acid) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 AUC of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 Cmax of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 Ctrough of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 CL of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 Vss of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 Tmax of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 T1/2 of KT-001(cationic lipids) in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer.
Time frame: 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 DOR in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Time frame: Through study completion, an average of 3 years.
To assess the DCR in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Time frame: Through study completion, an average of 3 years.
To assess the PFS in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Time frame: Through study completion, an average of 3 years.
To assess the OS in the treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Time frame: Through study completion, an average of 3 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Haining Huang study director
iLeukon
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ILKN421H and Pembrolizumab in people with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC), run by iLeukon Therapeutics, Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Haining Huang (858-209-6722, HHuang@Cytimm.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. (time frame: Up to 3 years.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.