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DRUG:

Lazcluze (lazertinib)

i
Other names: GNS-1480, YH25448, GNS 1480, YH-25448, YH 25448, JNJ-73841937, GNS1480, JNJ73841937, JNJ 73841937, JNJ-1937, JNJ1937, JNJ 1937
Company:
J&J, Oscotec, Yuhan Corp
Drug class:
EGFR inhibitor
Related drugs:
14d
New P2 trial • Combination therapy • Metastases
|
carboplatin • pemetrexed • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib) • amivantamab SC (Ami-LC)
17d
Lazertinib for NSCLC Harboring Activating EGFR Mutations in TKI naïve Patients (clinicaltrials.gov)
P2, N=150, Active, not recruiting, Myung-Ju Ahn | Recruiting --> Active, not recruiting
Enrollment closed
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EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion
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Lazcluze (lazertinib)
18d
Enrollment change • Adverse events • Metastases
|
EGFR (Epidermal growth factor receptor)
|
EGFR L858R • EGFR exon 19 deletion
|
Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib) • minocycline
22d
CHRYSALIS-2: A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov)
P1, N=701, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting | N=460 --> 701
Enrollment closed • Enrollment change
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR expression • MET expression • EGFR exon 20 mutation • EGFR expression + MET expression
|
Tagrisso (osimertinib) • carboplatin • pemetrexed • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
1m
Trial completion date
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M
|
Tagrisso (osimertinib) • Lazcluze (lazertinib) • amivantamab SC (Ami-LC)
1m
Updated overall survival and ctDNA analysis in patients with EGFR T790M-positive advanced non-small cell lung cancer treated with lazertinib in the phase 1/2 LASER201 study. (PubMed, BMC Med)
Lazertinib is a promising treatment option for patients with EGFR T790M-positive NSCLC following disease progression on prior EGFR-directed TKIs. Patients in LASER201 experienced prolonged OS, regardless of their EGFR mutation, brain metastases, or prior brain radiation status. Clearance of plasma EGFR mutations after lazertinib was associated with patient outcomes.
P1/2 data • Journal • Circulating tumor DNA • Metastases
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR T790M • EGFR positive
|
Lazcluze (lazertinib)
3ms
Lazertinib in EGFR-Variant Non-Small Cell Lung Cancer With CNS Failure to Prior EGFR Tyrosine Kinase Inhibitors: A Nonrandomized Controlled Trial. (PubMed, JAMA Oncol)
These results suggest that using lazertinib instead of brain local treatment could be a potential strategy in patients with EGFR-variant NSCLC whose CNS metastases progressed after prior EGFR TKI treatment. ClinicalTrials.gov Identifier: NCT05326425.
Journal
|
EGFR (Epidermal growth factor receptor)
|
Lazcluze (lazertinib)
3ms
Journal
|
EGFR (Epidermal growth factor receptor)
|
Lazcluze (lazertinib)
3ms
Trial completion date • Combination therapy • Metastases
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
Tagrisso (osimertinib) • carboplatin • pemetrexed • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
3ms
Trial completion date • Combination therapy • Metastases
|
EGFR (Epidermal growth factor receptor)
|
Tagrisso (osimertinib) • carboplatin • pemetrexed • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
3ms
Premedication to Reduce Amivantamab Associated Infusion Related Reactions (clinicaltrials.gov)
P2, N=74, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Aug 2026 --> Oct 2025
Trial completion date
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • dexamethasone • Lazcluze (lazertinib)
3ms
Trial completion date • Metastases
|
gefitinib • Lazcluze (lazertinib)
4ms
Potential Utility of a 4th-Generation EGFR-TKI and Exploration of Resistance Mechanisms-An In Vitro Study. (PubMed, Biomedicines)
Ba/F3 cells with an osimertinib-resistant secondary mutation were refractory to all 3G TKIs tested (alflutinib, lazertinib, rezivertinib, almonertinib, and befotertinib)...HCC827BIR cells had MET gene amplification and were sensitive to a combination of capmatinib (MET-TKI) and BI4020...This study suggests that erlotinib may be more suitable than 4G TKIs to overcome secondary mutations after front-line osimertinib. We found that off-target mechanisms that cause resistance to earlier-generation TKIs will also cause resistance to 4G TKIs.
Preclinical • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
Tagrisso (osimertinib) • erlotinib • Ameile (aumolertinib) • Tabrecta (capmatinib) • Ivesa (firmonertinib) • Lazcluze (lazertinib) • BI-4020 • Semena (befotertinib) • Rui Bi Da (rezivertinib)
4ms
Initial AXL and MCL-1 inhibition contributes to abolishing lazertinib tolerance in EGFR-mutant lung cancer cells. (PubMed, Cancer Sci)
Triple therapy with an MCL-1 or YAP inhibitor in combination with lazertinib and an AXL inhibitor significantly reduced cell viability and increased the apoptosis rate. These results demonstrate that AXL and YAP/MCL-1 signals contribute to adaptive lazertinib resistance in EGFR-mutant lung cancer cells, suggesting that the initial dual inhibition of AXL and YAP/MCL-1 might be a highly effective strategy in eliminating lazertinib-resistant cells.
Journal
|
EGFR (Epidermal growth factor receptor) • AXL (AXL Receptor Tyrosine Kinase)
|
Lazcluze (lazertinib)
4ms
MARIPOSA: A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov)
P3, N=1074, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Apr 2024 --> Aug 2023
Trial primary completion date • Combination therapy • Metastases
|
EGFR (Epidermal growth factor receptor)
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
4ms
Mechanisms of acquired resistance to first-line amivantamab plus lazertinib versus osimertinib in patients with EGFR-mutant advanced non-small cell lung cancer: An early analysis from the phase III MARIPOSA study (ESMO 2024)
Ami+laz had significantly lower rates of EGFR and MET resistance alterations with trends for lower rates of TP53 resistance mutations and RB1 loss compared with osi. These initial findings suggest that first-line ami+laz is changing the biology of acquired resistance and demonstrate clear proof of mechanism with potent inhibition of resistance via the EGFR and MET pathways.
Late-breaking abstract • P3 data • Preclinical • Clinical • Metastases
|
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • RB1 (RB Transcriptional Corepressor 1)
|
TP53 mutation • EGFR mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR C797S • RB1 mutation
|
Guardant360® CDx
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
5ms
Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA. (PubMed)
Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.
Journal • Metastases
|
Guardant360® CDx
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
5ms
Lazertinib versus Platinum-Based Chemotherapy with Epidermal Growth Factor Receptor (EGFR)-Positive Non-Small-Cell Lung Cancer after Failing EGFR-Tyrosine Kinase Inhibitor: A Real-World External Comparator Study. (PubMed, Cancers (Basel))
Based on this retrospective, external control study, lazertinib has demonstrated significantly better efficacy compared with platinum-based chemotherapy. The external controls provide important context to evaluate efficacy in single-arm studies.
Journal • Real-world evidence • Real-world
|
EGFR (Epidermal growth factor receptor)
|
Lazcluze (lazertinib)
5ms
Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC. (PubMed, N Engl J Med)
Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).
Journal • Metastases
|
EGFR (Epidermal growth factor receptor)
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
5ms
Comparative effectiveness of lazertinib in patients with EGFR T790M-positive non-small-cell lung cancer using a real-world external control. (PubMed, Sci Rep)
The median overall survival with lazertinib was not reached and that with osimertinib was 29.8 months (HR 0.44; 95% CI 0.25-0.77, p = 0.005). Our study suggests that lazertinib has an ORR and PFS comparable to those of osimertinib and has the potential for superior survival benefits.
Clinical • Journal • HEOR • Real-world evidence • Real-world
|
EGFR (Epidermal growth factor receptor)
|
Tagrisso (osimertinib) • Lazcluze (lazertinib)
5ms
Subcutaneous versus Intravenous Amivantamab, both in Combination with Lazertinib, in Refractory EGFR-mutated NSCLC: Primary Results from the Phase 3 PALOMA-3 Study. (PubMed, J Clin Oncol)
Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced infusion-related reactions, increased convenience, and prolonged survival.
P3 data • Journal • Combination therapy
|
EGFR (Epidermal growth factor receptor)
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib) • amivantamab SC (Ami-LC)
6ms
ATTLAS, IMpower151 and ORIENT-31: Dusting off IMpower150 for Post-Osimertinib in EGFR-Mutated NSCLC? (PubMed, Lung Cancer (Auckl))
The retrospective subgroup analysis of IMpower150 indicated that the quad regimen (carboplatin, paclitaxel, bevacizumab, atezolizumab) improved PFS and overall survival (OS) in patients with EGFR-mutant NSCLC who progressed on first-generation EGFR-TKIs...MARIPOSA-2 provided the first randomized trial post-osimertinib in EGFR-mutant NSCLC patients with another quad regimen (platinum, pemetrexed, lazertinib, amivantamab)...Here, we discuss how the results of IMpower151 and ATTLAS may rejuvenate interest in a non-EGFR containing quad regimen as a potential post-osimertinib monotherapy treatment. Randomized trials comparing the results of these studies, including the quad regimen of MARIPOSA-2 versus the quad regimen of IMpower151/Impower150/ATTLAS in post-osimertinib (or other 3G EGFR-TKI) progression, are urgently needed.
Journal • PD(L)-1 Biomarker
|
EGFR (Epidermal growth factor receptor)
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Avastin (bevacizumab) • Tagrisso (osimertinib) • Tecentriq (atezolizumab) • carboplatin • paclitaxel • pemetrexed • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
6ms
Trial primary completion date • Metastases
|
EGFR (Epidermal growth factor receptor)
|
Tagrisso (osimertinib) • carboplatin • pemetrexed • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib) • amivantamab SC (Ami-LC)
6ms
PALOMA: A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (clinicaltrials.gov)
P1, N=160, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting
Enrollment closed
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR exon 20 insertion • EGFR exon 20 mutation
|
Lazcluze (lazertinib) • amivantamab SC (Ami-LC)
7ms
Enrollment change • Adverse events • Metastases
|
EGFR (Epidermal growth factor receptor)
|
EGFR L858R • EGFR exon 19 deletion
|
Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib) • minocycline
7ms
Amivantamab plus lazertinib in atypical EGFR-mutated advanced non-small cell lung cancer (NSCLC): Results from CHRYSALIS-2. (ASCO 2024)
Research Funding: Janssen Global Services LLC. In the largest, single-cohort, prospective study of atypical EGFR-mutated advanced NSCLC, ami+laz demonstrated clinically meaningful and durable antitumor activity in pts who were treatment-naïve or had disease progression on afatinib.
Metastases
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation
|
Gilotrif (afatinib) • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
7ms
Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced non-small cell lung cancer (NSCLC) with biomarkers of high-risk disease: A secondary analysis from the phase 3 MARIPOSA study. (ASCO 2024)
Ami+laz demonstrated significantly improved mPFS vs osi in pts with biomarkers of high-risk disease. Given these features can occur in up to 85% of pts, ami+laz represents an important new standard of care for treatment-naïve EGFR-mutant advanced NSCLC.
P3 data • Clinical • Metastases
|
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53)
|
EGFR mutation
|
Guardant360® CDx
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
7ms
Subcutaneous amivantamab vs intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results, including overall survival (OS), from the global, phase 3, randomized controlled PALOMA-3 trial. (ASCO 2024)
PALOMA-3 (NCT05388669) evaluated SC ami+laz vs IV ami+laz for pharmacokinetics (PK), efficacy, and safety among pts with EGFR Ex19del or L858R-mutated advanced NSCLC and disease progression on osimertinib and platinum-based chemotherapy. SC ami demonstrated noninferior PK and ORR compared to IV. Unexpectedly, DoR, PFS, and OS were longer in the SC arm vs IV, suggesting that the route of administration or formulation may affect outcomes. The safety profile was improved for SC ami, with lower IRR and VTE rates.
Combination therapy • Late-breaking abstract • P3 data • Clinical • Metastases
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib) • amivantamab SC (Ami-LC)
7ms
Premedication to Reduce Amivantamab Associated Infusion Related Reactions (clinicaltrials.gov)
P2, N=74, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting
Enrollment closed
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • dexamethasone • Lazcluze (lazertinib)
7ms
MARIPOSA: Can Amivantamab and Lazertinib Replace Osimertinib in the Front-Line Setting? (PubMed, Lung Cancer (Auckl))
The MARIPOSA trial was designed to study if the combination of amivantamab plus lazertinib in untreated epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients would provide improved progression-free survival. Here, we discuss the rationale for the study and the early results of MARIPOSA.
Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
8ms
A Real-World Study of Patient Characteristics and Clinical Outcomes in EGFR Mutated Lung Cancer Treated with First-Line Osimertinib: Expanding the FLAURA Trial Results into Routine Clinical Practice. (PubMed, Cancers (Basel))
Our data support the use of osimertinib in real-word settings and highlight the need for designing registration trials that are more inclusive of patient/disease characteristics seen in routine clinical practice. It is yet to be determined if the use of evolving first-line EGFR inhibitor combination strategies (either platinum-doublet chemotherapy plus osimertinib or amivantamab plus lazertinib) will similarly translate from clinical trials to real-word settings.
Clinical data • Journal • Real-world evidence • Real-world
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
8ms
PALOMA: A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (clinicaltrials.gov)
P1, N=166, Recruiting, Janssen Research & Development, LLC | Trial primary completion date: Jan 2024 --> Oct 2024
Trial primary completion date • Metastases
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR exon 20 insertion • EGFR exon 20 mutation
|
Lazcluze (lazertinib) • amivantamab SC (Ami-LC)
8ms
CHRYSALIS: Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov)
P1, N=751, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2024 --> Jun 2025
Trial completion date • Metastases
|
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR exon 20 insertion • EGFR wild-type • MET exon 14 mutation • EGFR C797S • MET mutation • MET expression • EGFR exon 20 mutation • EGFR positive
|
carboplatin • pemetrexed • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
9ms
Lazertinib as a frontline treatment in patients with EGFR-mutated advanced non-small cell lung cancer: Long-term follow-up results from LASER201. (PubMed, Lung Cancer)
This analysis demonstrated long-term clinical benefit with lazertinib 240 mg in patients with EGFR-mutated NSCLC who had not previously received EGFR TKIs. The safety profile for lazertinib was tolerable and consistent with that previously reported.
Journal • Metastases
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR G719X
|
Lazcluze (lazertinib)
9ms
Premedication to Reduce Amivantamab Associated Infusion Related Reactions (clinicaltrials.gov)
P2, N=67, Recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2025 --> Aug 2026
Trial completion date
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • dexamethasone • Lazcluze (lazertinib)
9ms
Enrollment open
|
EGFR (Epidermal growth factor receptor)
|
EGFR L858R • EGFR exon 19 deletion
|
Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib) • minocycline
9ms
New P2 trial
|
carboplatin • pemetrexed • Lazcluze (lazertinib)
9ms
PALOMA: A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (clinicaltrials.gov)
P1, N=166, Recruiting, Janssen Research & Development, LLC | Trial completion date: Feb 2025 --> Oct 2025
Trial completion date • Metastases
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR exon 20 insertion • EGFR exon 20 mutation
|
Lazcluze (lazertinib) • amivantamab SC (Ami-LC)
9ms
MARIPOSA-2: Is the treatment worse than the disease? (PubMed, Med)
Passaro et al.1 demonstrated in EGFR+ NSCLC post-1L osimertinib both "quad" (lazertinib [L] + amivantamab [A] + chemotherapy [CP]) and "triplet" (ACP) regimens achieved improved median progression-free survival over CP. Nonetheless, a high incidence of adverse events requiring dose modifications may limit adaptation of the triplet and quad MARIPOSA-2 regimens.
Journal
|
EGFR (Epidermal growth factor receptor)
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Lazcluze (lazertinib)
11ms
Enrollment change • Metastases
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR exon 20 insertion • EGFR exon 20 mutation
|
Lazcluze (lazertinib) • amivantamab SC (Ami-LC)
11ms
Premedication to Reduce Amivantamab Associated Infusion Related Reactions (clinicaltrials.gov)
P2, N=67, Recruiting, Janssen Research & Development, LLC | N=126 --> 67
Enrollment change
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion
|
Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • dexamethasone • Lazcluze (lazertinib)
11ms
Trial completion date • Metastases
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M
|
Tagrisso (osimertinib) • Lazcluze (lazertinib) • amivantamab SC (Ami-LC)