Phase 2
Completed N=29
A Study of Lazertinib in Participants With Epidermal Growth Factor Receptor (EGFR) Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
Source: ClinicalTrials.gov NCT04075396 ↗Enrolled (actual)
29
Serious AEs
57.1%
Results posted
Feb 2024
Primary outcomePrimary: Part D: Number of Participants With Treatment-emergent Adverse Events (TEAEs) — 15; 13 Participants
Summary
The main purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of Lazertinib when given orally to participants with epidermal growth factor receptor single activating mutation positive (EGFRm+) locally advanced or metastatic Non Small Cell Lung Cancer (NSCLC).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part D: Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
15; 13 | — |
| PRIMARY Part D: Number of Participants With Clinically Significant Abnormalities in Vital Signs |
0; 0 | — |
| PRIMARY Part D: Number of Participants With Clinically Significant Abnormalities in Physical Examination |
8; 2 | — |
| PRIMARY Part D: Number of Participants With Greater Than or Equal to (>=) Grade 4 Toxicity in Laboratory Tests Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v) 4.03 |
2; 0 | — |
| PRIMARY Part D: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Tests |
1; 1 | — |
| PRIMARY Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-last]) for Single Dose of Lazertinib |
5907.56; 7664.99 | — |
| PRIMARY Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) for Single Dose of Lazertinib |
6504.88; 8869.21 | — |
| PRIMARY Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) for Single Dose of Lazertinib |
3253.58; 4097.34 | — |
| PRIMARY Part D: Maximum Observed Plasma Concentration (Cmax) for Single Dose of Lazertinib |
441.04; 524.13 | — |
| PRIMARY Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Single Dose of Lazertinib |
2.00; 2.50 | — |
| PRIMARY Part D: Apparent Terminal Half-Life (t1/2) for Single Dose of Lazertinib |
51.12; 63.98 | — |
| PRIMARY Part D: Apparent Terminal Elimination Rate Constant (Lambda[z]) for Single Dose of Lazertinib |
0.02; 0.01 | — |
| PRIMARY Part D: Apparent Plasma Clearance (CL/F) for Single Dose of Lazertinib |
41.92; 39.38 | — |
| PRIMARY Part D: Apparent Volume of Distribution (Vd/F) for Single Dose of Lazertinib |
2990.36; 3822.19 | — |
| PRIMARY Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the End of Dosing Interval at Steady State (AUCss[0-last]) for Multiple Dose of Lazertinib |
7025.10; 9249.58 | — |
| PRIMARY Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Multiple Dose of Lazertinib |
509.92; 632.00 | — |
| PRIMARY Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) for Multiple Dose of Lazertinib |
3.15; 3.97 | — |
| PRIMARY Part D: Accumulation Ratio (Rac) for Multiple Dose of Lazertinib |
2.26; 2.36 | — |
| PRIMARY Part D: Apparent Plasma Clearance at Steady State (CLss/F) for Multiple Dose of Lazertinib |
44.25; 50.10 | — |
| PRIMARY Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 1 |
6.41; 10.91 | — |
| PRIMARY Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 8 |
154.62; 225.47 | — |
| PRIMARY Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 15 |
177.40; 263.74 | — |
| SECONDARY Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-last]) of Metabolite M7 After Single Dose of Lazertinib |
216.350; 208.908 | — |
| SECONDARY Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of Metabolite M7 After Single Dose of Lazertinib |
281.172; 263.373 | — |
| SECONDARY Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Metabolite M7 After Single Dose of Lazertinib |
86.692; 74.523 | — |
| SECONDARY Part D: Maximum Observed Plasma Concentration (Cmax) of Metabolite M7 After Single Dose of Lazertinib |
5.838; 4.774 | — |
| SECONDARY Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite M7 After Single Dose of Lazertinib |
4.020; 4.150 | — |
| SECONDARY Part D: Apparent Terminal Half-Life (t1/2) of Metabolite M7 After Single Dose of Lazertinib |
41.205; 50.019 | — |
| SECONDARY Part D: Apparent Terminal Elimination Rate Constant (Lambda [z]) of Metabolite M7 After Single Dose of Lazertinib |
0.017; 0.021 | — |
| SECONDARY Part D: Metabolic Ratio (MR) of Metabolite M7 and Lazertinib After Single Dose of Lazertinib |
0.042; 0.027 | — |
| SECONDARY Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the End of Dosing Interval at Steady State (AUCss[0-last]) of Metabolite M7 After Multiple Dose of Lazertinib |
148.335; 168.765 | — |
| SECONDARY Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib |
7.866; 8.319 | — |
| SECONDARY Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib |
6.330; 4.350 | — |
| SECONDARY Part D: Accumulation Ratio (Rac) of Metabolite M7 After Multiple Dose of Lazertinib |
1.976; 2.270 | — |
| SECONDARY Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8 and 15 of Cycle 1 |
0.257; 0.358; 4.928; 5.791; 5.356; 6.340 | — |
| SECONDARY Part D: Metabolic Ratio at Steady State (MRss) of Metabolite M7 and Lazertinib After Multiple Dose of Lazertinib |
0.021; 0.016 | — |
| SECONDARY Objective Response Rate (ORR) |
26.7; 7.7 | — |
| SECONDARY Duration of Response (DoR) |
NA; 2.8 | — |
| SECONDARY Disease Control Rate (DCR) |
60.0; 53.8 | — |
| SECONDARY Percentage Change From Baseline in Tumor Size |
-5.37; 9.56 | — |
| SECONDARY Progression Free Survival (PFS) |
3.1; 4.2 | — |
| SECONDARY Overall Survival (OS) |
9.1; 7.7 | — |
Eligibility Criteria
Inclusion Criteria
- Females should agree to use adequate contraceptive measure, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of following criteria at screening; Post-menopausal defined as aged more than 50 years and ameorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments; Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation; Women under 50 years old would be considered postmenopausal if they have been ameorrhoeic for at least 12 months following cessation of exogenous hormonal treatment, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in postmenopausal range for the institution
- Male participants who have not undergone a vasectomy must agree to use barrier contraception that is, condoms, and refrain from donating sperm until 3 months after last drug is taken
- During the study, and for 3 months after receiving the last dose of study drug, female participants must agree not to donate eggs (ova, oocytes) and male participants must agree not to donate sperm for the purposes of assisted reproduction
- In Part D: Participants outside Korea with histologically or cytologically (that is, using pleural effusion, ascites) confirmed Non-Small Cell Lung Cancer (NSCLC) with previously diagnosed epidermal growth factor receptor single activating mutation positive (EGFRm+), and who have had progressive disease on prior epidermal growth factor receptor- Tyrosine kinase inhibitor (EGFR-TKI) therapy
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 3 months
Exclusion Criteria
- An unapproved investigational product from another clinical study within 30 days of the first dose of study treatment
- Treatment with an EGFR TKIs (example: erlotinib or gefitinib) within 8 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment or other investigational products within approved indication of marketed product (if sufficient wash-out time has not occurred due to schedule or PK properties, an alternative appropriate wash-out time based on known duration of time to reversibility of drug related adverse events could be agreed upon by sponsor and the Investigator)
- Any cytotoxic chemotherapy or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen within 14 days of the first dose of study treatment
- Symptomatic spinal cord compression (if steroid treatment is not required within at least 2 weeks prior to the start of the study treatment then the participant may be enrolled)
- Brain metastases with symptomatic and/or requiring emergency treatment (example; Steroid for at least 2 weeks prior to start of study treatment)
Data sourced from ClinicalTrials.gov (NCT04075396). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.