Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication LAZCLUZE, in combination with amivantamab, is indicated for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test [see Dosage and Administration (2.1) ] . FDA label
Also known as JNJ-73841937, YH25448
Lazertinib · 4 trials · 2 indications
Ctrough was the observed serum concentration of Amivantamab at steady state immediately prior to the next drug administration.
Ctrough was the observed serum concentration of Amivantamab immediately prior to the next drug administration.
AUC (Day 1-15) defined as area under the concentration time curve from Cycle 2 Day 1 to Day 15 were reported.
PFS is defined as the time from randomization until the date of objective disease progression or death, whichever came first, as assessed by BICR according to RECIST version 1.1. Progressed disease: Sum of diameters increased by greater than or equal to (\>=)20 percent (%) and \>=5 millimeter (mm) from nadir (including baseline if it was smallest sum).
Follow-up for the extension cohort is still ongoing and thus results from the analysis that includes the extension cohort will be reported up on study completion.
An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were defined as AEs that started on or after the first dose of study medication and prior to 28-day follow-up period. All TEAEs including serious and non-serious events are reported in this outcome measure.
Number of participants with clinically significant abnormalities in vital signs were reported. Vital signs included pulse rate, systolic blood pressure, diastolic blood pressure, body temperature, height, weight, and body mass index (BMI). Baseline was defined as last non-missing measurement taken prior to reference start date.
Number of participants with clinically significant abnormalities in physical examination were reported. Physical examination included general appearance, skin, head and neck (including ears, eyes, nose and throat), respiratory, cardiovascular, abdomen, lymph nodes, thyroid, muscular-skeletal (including spine and extremities) and neurological systems. Baseline was defined as last non-missing measurement taken prior to reference start date.
Safety laboratory assessments included clinical chemistry, hematology and urinalysis. Grading was done as per NCI CTCAE version 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. Baseline was defined as last non-missing measurement taken prior to reference start date.
Number of participants with clinically significant abnormalities in electrocardiogram (ECG) tests were reported. ECG variables included heart rate, PR interval, RR interval, QRS interval, QT interval and Fridericia-corrected QT interval (QTcF). Baseline was defined as last non-missing measurement taken prior to reference start date.
AUC(0-last) was defined as area under the plasma concentration-time curve from time zero to time of last quantifiable concentration. AUC(0-last) for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method.
AUC(0-infinity) was defined as area under the plasma concentration time curve from time zero to infinite time. AUC(0-infinity) for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
AUC(0-24) was defined as area under the plasma concentration time curve from time zero to 24 hours. AUC(0-24) for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Cmax was defined as maximum observed plasma concentration. Cmax for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Tmax was defined as time to reach the maximum observed plasma concentration. Tmax for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
T1/2 was defined the time measured for the plasma concentration of a drug to decrease by half of its initial concentration. T1/2 for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Lambda(z) was defined as terminal elimination rate constant. Lambda(z) for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
CL/F was defined as apparent plasma clearance. CL/F for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Vd/F was defined as apparent volume of distribution. Vd/F for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
AUCss(0-last) was defined as area under the plasma concentration time curve from time zero to end of dosing interval at steady state. AUCss(0-last) for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Cmax,ss was defined as maximum observed plasma concentration at steady state. Cmax,ss for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Tmax,ss was defined as time to reach maximum observed plasma concentration at steady state. Tmax,ss for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Accumulation ratio was calculated as AUCss(0-last) divided by AUC(0-24), where AUCss(0-last) was defined as area under the plasma concentration time curve from time zero to end of dosing interval at steady state and AUC(0-24) was defined area under the plasma concentration time curve from time zero to 24 hours time. Rac for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
CLss/F was defined as apparent plasma clearance at steady state. CLss/F for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 1 was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 8 was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 15 was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.
DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.
ORR is defined as the percentage of participants who achieve either a complete (CR) or partial response (PR) as determined by the investigator using RECIST 1.1 criteria.
Adverse events (AEs) defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Criteria Version 5.0 in participants treated at the RP2CD regimen of Lazertinib and Amivantamab combination therapy. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
DLTs are defined as certain non-hematologic and hematologic toxicities of Grade 3 or higher.
AEs defined by the NCI-CTCAE criteria version 5.0 in participants treated with LACP combination regimen. An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
ORR is defined as the percentage of participants who achieve either a complete (CR) or partial response (PR) as determined by the investigator using RECIST 1.1 criteria with Next Generation Sequencing (NGS) Analysis of Circulating Tumor Deoxyribonucleic Acid (ctDNA), Immunohistochemical (IHC) Analysis of Tumor Epidermal Growth Factor Receptor (EGFR) and MET Expression (Phase 1b Expansion Cohort D).
ORR among participants with MET3+ staining on \>=25 % of tumor cells will be reported. ORR is defined as the percentage of participants who achieve either a CR or PR as determined by the investigator using RECIST 1.1 criteria.
DOR among participants with MET3+ staining on \>=25 % of tumor cells will be reported. DOR will be calculated as time from initial response of CR or PR to progressive disease (PD) or death due to any cause, whichever comes first, only for participants who achieve CR or PR as determined by the investigator using RECIST 1.1 criteria.
CBR among participants with MET3+ staining on \>=25% of tumor cells will be reported. CBR is defined as the percentage of participants achieving complete or partial response, or durable stable disease (duration of at least 11 weeks) as determined by the investigator using RECIST 1.1 criteria.
| Arm | Type | Description |
|---|---|---|
| Arm A: Lazertinib with Amivantamab SC-CF | EXPERIMENTAL | Lazertinib 240 milligrams (mg) will be administered orally once daily. Participants will receive amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), 1600 mg/ 2240 mg depending on the body weight by manual injection. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the long-term extension (LTE) Phase. |
| Arm B: Lazertinib with Amivantamab Intravenous (IV) Infusion | EXPERIMENTAL | Lazertinib 240 mg will be administered orally once. Participants will receive amivantamab, 1050 mg or 1400 mg depending on the body weight as an IV infusion. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the LTE Phase. |
| Arm A: LACP/ACP-L | EXPERIMENTAL | LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. |
| Arm B: CP (Carboplatin and Pemetrexed) | ACTIVE_COMPARATOR | Participants will receive Pemetrexed in combination with Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Pemetrexed as maintenance until disease progression. |
| Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed) | EXPERIMENTAL | Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression. |
| Arm A2 (Extension Cohort): ACP-L | EXPERIMENTAL | Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression. |
| Arm C2 (Extension Cohort): ACP | EXPERIMENTAL | Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression. |
| Part D: Outside of Korea | EXPERIMENTAL | Participants from outside of Korea with progressive disease and on prior epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) therapy will receive recommended phase 2 doses based on safety, tolerability, efficacy and pharmacokinetics (PK) of Lazertinib. |
| Phase 1 (monotherapy dose escalation): Lazertinib | EXPERIMENTAL | Participants will receive Lazertinib monotherapy orally once daily (QD) in 21-day cycles until documented evidence of disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first. The subsequent doses of Lazertinib will be assigned by the Study Evaluation Team (SET) according to the dose escalation strategy by Bayesian logistic regression model (BLRM). |
| Phase 1b (combination): Lazertinib and Amivantamab | EXPERIMENTAL | Participants will receive Lazertinib and Amivantamab, after the safety of RP2D of Lazertinib is confirmed in the Phase 1, in 28-day cycles until documented evidence of disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent, or the investigator decides to discontinue treatment, whichever comes first. This phase will start enrolling participants after the safety of Amivantamab is confirmed in Japanese participants in Study 61186372EDI1001 (NCT02609776). |
| Phase 1b (combination): Lazertinib, Amivantamab and Platinum-doublet Chemotherapy (LACP) | EXPERIMENTAL | Participants will receive Lazertinib starting dose administered orally once daily (QD) in combination with Amivantamab, and doses of platinum-based chemotherapy (carboplatin and pemetrexed) per standard of care according to local guidance in a 21-day cycle for 4 cycles followed by maintenance with Lazertinib, Amivantamab and pemetrexed until disease progression or unacceptable toxicities. |
| Phase 1b (expansion) Cohort A: Lazertinib and Amivantamab | EXPERIMENTAL | This cohort A will further characterize the safety, tolerability, and preliminary antitumor activity of Lazertinib and Amivantamab based combinations within specific NSCLC population "who have progressed after osimertinib and subsequent platinum-based chemotherapy, and platinum-based chemotherapy regimen as the last line of therapy prior to study enrollment. Prior use of first or second generation EGFR TKI is allowed if administered prior to osimertinib. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter. |
| Phase 1b (expansion) Cohort B: Lazertinib and Amivantamab | EXPERIMENTAL | This Cohort B will further characterize the safety, tolerability and preliminary antitumor activity of Lazertinib and JNJ-61186372 combination in participants previously treated with advanced or metastatic NSCLC with documented primary EGFR Exon 20ins activating mutation. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter. |
| Phase 1b (expansion) Cohort C: Lazertinib and Amivantamab | EXPERIMENTAL | This Cohort C will further characterize the safety, tolerability and preliminary antitumor activity of Lazertinib and JNJ-61186372 combination in participants with uncommon EGFR mutations. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter. |
| Phase 1b (expansion) Cohort D: Lazertinib and Amivantamab | EXPERIMENTAL | Cohort D will seek to validate one or both potential biomarker strategies (next generation sequencing \[NGS\] and Immunohistochemical \[IHC\]), previously identified in Cohort E of Study 61186372EDI1001, in participants with osimertinib-relapsed, but chemotherapy-naive, EGFR Exon19del or L858R mutated NSCLC. Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter. |
| Phase 1b (expansion) Cohort E: Lazertinib and Amivantamab | EXPERIMENTAL | Participants will receive at the RP2CD of Lazertinib orally QD and Amivantamab, every 7 days for the first 28 days cycle and every 2 weeks thereafter. Cohort E will seek to validate the immunohistochemical (IHC)-based biomarker strategy, by characterizing the activity of Amivantamab and Lazertinib combination in biomarker-positive participants with osimertinib-relapsed, but chemotherapy-naïve, EGFR Exon19del or L858R mutated NSCLC. In addition, Cohort E will seek to collect prospective data to confirm that prophylactic anticoagulation safely and effectively decreases the incidence of VTE events for patients treated with the combination of Amivantamab and Lazertinib, using Cohort F as reference. |
| Phase 1b (expansion) Cohort F: Amivantamab Monotherapy | EXPERIMENTAL | Participants will receive Amivantamab monotherapy once weekly (QW) for 4 weeks, then every 2 weeks thereafter. Cohort F will seek to validate the IHC-based biomarker strategy, previously identified in Cohort D, by characterizing the activity of JNJ-61186372 monotherapy (Cohort F) in biomarker-positive participants with osimertinib-relapsed, but chemotherapy-naïve, EGFR Exon19del or L858R mutated NSCLC. |
| Name | Type | Description |
|---|---|---|
| Lazertinib | DRUG | Lazertinib tablets will be administered orally. |
| Amivantamab Subcutaneous and Co-Formulated with Recombinant Human Hyaluronidase (SC CF) | DRUG | Amivantamab injection will be administered subcutaneously by manual injection. |
| Amivantamab Intravenous | DRUG | Amivantamab will be administered by IV infusion. |
| Amivantamab | DRUG | Amivantamab will be administered as an IV infusion. |
| Pemetrexed | DRUG | Pemetrexed will be administered as an IV infusion. |
| Carboplatin | DRUG | Carboplatin will be administered as an IV infusion. |
Inclusion Criteria: * Have histologically or cytologically confirmed, advanced or metastatic non-small cell lung cancer (NSCLC), characterized by either epidermal growth factor receptor (EGFR) Exon 19 deletion (Exon 19del) or Exon 21 leucine 858 to arginine substitution (Exon 21 L858R) mutation by ...
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Lazertinib is an investigational small molecule being studied for advanced or metastatic non-small cell lung cancer, including EGFR-mutated disease. It is being evaluated both as monotherapy and in combination with amivantamab, including after osimertinib failure. It is not yet approved and remains in clinical development.
Lazertinib targets EGFR, the epidermal growth factor receptor. It is an EGFR inhibitor, a small molecule designed to act on EGFR-mutated non-small cell lung cancer. The clinical program is biomarker selected, enrolling participants with EGFR-mutated advanced or metastatic disease.
Lazertinib is being developed by Johnson & Johnson, which trades under the ticker JNJ. The company is running the clinical program across multiple countries, including the United States, China, Japan, South Korea, and several European nations.
Lazertinib is in Phase 3 development. Two Phase 3 trials are active, alongside an active Phase 1 combination study and a completed Phase 1 monotherapy study. It is investigational and has not been approved; the program includes 1,506 enrolled participants across four trials.
Lazertinib is being studied in NCT05388669, a Phase 3 trial of subcutaneous versus intravenous amivantamab in EGFR-mutated advanced or metastatic NSCLC, and NCT04988295, a Phase 3 trial combining amivantamab and lazertinib with platinum chemotherapy after osimertinib failure. Earlier studies include NCT04077463 and NCT04075396.