Lazcluze (lazertinib) / J&J 
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  • ||||||||||  Rybrevant (amivantamab-vmjw) / J&J, Lazcluze (lazertinib) / J&J
    Journal:  The potential of lazertinib and amivantamab combination therapy as a treatment strategy for uncommon EGFR-mutated NSCLC. (Pubmed Central) -  Feb 19, 2025   
    P1
    Different toxicity profiles and sequential strategies were considered, together with efficacy results, to reach common considerations for the front-line treatment strategies in EGFR mutant NSCLC, however clinical research should be prioritized to identify further selection features. Notably, the combination surpasses afatinib, a first-line treatment for uncommon EGFR mutations in NSCLC, in terms of in
  • ||||||||||  Review, Journal:  The User's Guide to Amivantamab. (Pubmed Central) -  Feb 4, 2025   
    This work reviews the mechanism of action, pharmacology, clinical trial data, and covers management of toxicities. This guide is designed as a practical reference tool for clinicians, pharmacists, and basic science researchers.
  • ||||||||||  Rybrevant (amivantamab-vmjw) / J&J, Tagrisso (osimertinib) / AstraZeneca, Lazcluze (lazertinib) / J&J
    Decoding First-line strategies in EGFR-mutated NSCLC: A Computational Analysis of FLAURA2 vs. MARIPOSA (Grand Ballroom A-C) -  Jan 28, 2025 - Abstract #IASLCTTLC2025IASLC_TTLC_182;    
    As we await randomized studies to compare these strategies, here we demonstrate the potential of such computational analysis to aid in clinical decision making, especially in settings where multiple treatment options are currently approved. Figures: Not to be submitted with abstract, will include in poster.
  • ||||||||||  Rybrevant (amivantamab-vmjw) / J&J, Tagrisso (osimertinib) / AstraZeneca, Lazcluze (lazertinib) / J&J
    Exploring the Time Toxicity of frontline regimens for treatment of EGFR mutated NSCLC (Grand Ballroom A-C) -  Jan 28, 2025 - Abstract #IASLCTTLC2025IASLC_TTLC_171;    
    The estimated time toxicity across treatment regimens highlights a significant increase in healthcare burden with combination strategies compared to osimertinib monotherapy. These findings emphasize the need to consider time toxicity while aiming to balance the benefits of progression-free survival associated with each regimen.
  • ||||||||||  Rybrevant (amivantamab-vmjw) / J&J, Tagrisso (osimertinib) / AstraZeneca, Lazcluze (lazertinib) / J&J
    Time toxicity of front-line treatments for patients with EGFR-mutated NSCLC (Grand Ballroom D-G) -  Jan 28, 2025 - Abstract #IASLCTTLC2025IASLC_TTLC_152;    
    We observed increased time toxicity, both in days and as a proportion of survival, with the combination regimens compared to osimertinib monotherapy. While there are modest survival benefits with the combination regimens, these should be weighed against the increased time toxicity for patients.
  • ||||||||||  Lazcluze (lazertinib) / J&J
    Review, Journal:  Lazertinib: breaking the mold of third-generation EGFR inhibitors. (Pubmed Central) -  Jan 27, 2025   
    This review delves into the discovery and development of lazertinib underscoring the improvements in medicinal chemistry properties, especially in comparison with osimertinib...The structural basis for the selectivity against the T790M mutation is enabled by the substituted pyrazole moiety, which facilitates both van der Waals and H-bonding interactions with the EGFR kinase domain. Insights from this case study offer lessons that can inform the future design of kinase inhibitors with improved safety and efficacy profiles for cancer treatment and other diseases.
  • ||||||||||  Rybrevant (amivantamab-vmjw) / J&J
    Trial primary completion date:  SKIPPirr: Premedication to Reduce Amivantamab Associated Infusion Related Reactions (clinicaltrials.gov) -  Jan 10, 2025   
    P2,  N=73, Active, not recruiting, 
    However, the increased incidence of AEs necessitates careful consideration. Trial primary completion date: Dec 2024 --> Mar 2024
  • ||||||||||  Review, Journal, PD(L)-1 Biomarker, IO biomarker:  Emerging Therapies for Brain Metastases in NSCLC, Breast Cancer, and Melanoma: A Critical Review. (Pubmed Central) -  Dec 3, 2024   
    For melanoma, the combination of immune checkpoint inhibitors such as nivolumab and ipilimumab has proven effective in enhancing survival for patients with BM, both in BRAF-mutant and wild-type cases...Future research should optimise combination therapies, overcome resistance, and refine treatment sequencing. Continued emphasis on personalized, biomarker-driven approaches offers the potential to further improve outcomes, even for complex cases.
  • ||||||||||  Rybrevant (amivantamab-vmjw) / J&J, Tagrisso (osimertinib) / AstraZeneca, Lazcluze (lazertinib) / J&J
    Clinical, Retrospective data, Journal, Metastases:  EGFR-TKIs or EGFR-TKIs combination treatments for untreated advanced EGFR-mutated NSCLC: a network meta-analysis. (Pubmed Central) -  Nov 14, 2024   
    These results reveal that osimertinib plus chemotherapy and lazertinib plus amivantamab are superior first-line options for patients with advanced EGFR-mutated NSCLC. However, these combinations are associated with higher adverse event rates.
  • ||||||||||  Lazcluze (lazertinib) / J&J
    Enrollment closed:  Lazertinib for NSCLC Harboring Activating EGFR Mutations in TKI na (clinicaltrials.gov) -  Oct 29, 2024   
    P2,  N=150, Active, not recruiting, 
    However, these combinations are associated with higher adverse event rates. Recruiting --> Active, not recruiting
  • ||||||||||  Rybrevant (amivantamab-vmjw) / J&J, Lazcluze (lazertinib) / J&J
    Journal, Metastases:  Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC. (Pubmed Central) -  Oct 23, 2024   
    P3
    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.).
  • ||||||||||  Lazcluze (lazertinib) / J&J
    Focusing on the Radiation Oncologist Perspective (CRYSTAL 3; 3F) -  Oct 21, 2024 - Abstract #KATRDIC2024KATRDIC_76;    
    Currently we have performed a Multicenter Two-arm, Phase II Trial Assessing the Safety and Efficacy of First-line Lazertinib and Locally Ablative Radiotherapy in Patients with Synchronous Oligo-metastatic EGFR-mutant Non- small Cell Lung Cancer (ABLATE, KCSG-LU21-11). I would like to share the clinical experience of performing the trial from a radiation oncologist
  • ||||||||||  Rybrevant (amivantamab-vmjw) / J&J, Lazcluze (lazertinib) / J&J
    INTERSTITIAL PNEUMONITIS IN NON-SMALL CELL LUNG CANCER PATIENTS TREATED WITH LAZERTINIB, AMIVANTAMAB AND MINOCYCLINE () -  Aug 27, 2024 - Abstract #MTS2024MTS_281;    
    He received intravenous methylprednisolone and broad-spectrum antibiotics but passed away on day 6 of hospitalization due to severe pneumonia with unresolved fast atrial fibrillation...In the MARIPOSA study, the incidence of pneumonitis did not differ between the Lazertinib- Amivantamab group and the Osimertinib group...It remains unknown at this point as to whether minocycline use alone and/or a 3-drug combination is responsible for severe pneumonitis in our patients. Further observation and studies are eagerly needed to ensure a better clinical outcome.
  • ||||||||||  Managing EGFR, ALK and ROS1 resistance post 3rd generation TKI (Hall 301, Level 3) -  Aug 27, 2024 - Abstract #MTS2024MTS_17;    
    In ROS1-rearranged NSCLC, G2032R is the most common on-target resistance mutations which confers resistance to not only crizotinib but also to entrectinib and lorlatinib. Promising preclinical activity (repotrectinib and taletrectinib) and clinical efficacy (repotrectinib) against G2032R have been observed with these next-generation ROS1/TRK/ALK-TKIs.
  • ||||||||||  Rybrevant (amivantamab-vmjw) / J&J
    Subcutaneous vs Intravenous Amivantamab: Patient Satisfaction and Resource Utilization Results from the PALOMA-3 Study (20D) -  Aug 11, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_2761;    
    P3
    Conclusions : Intravenous amivantamab has demonstrated superior efficacy across multiple patient populations. Subcutaneous amivantamab provides the additional advantages of lower resource utilization and significantly higher patient satisfaction, and offers a convenient mode of administration for patients and healthcare providers, improving overall treatment experience.
  • ||||||||||  Rybrevant (amivantamab-vmjw) / J&J, Tagrisso (osimertinib) / AstraZeneca, Lazcluze (lazertinib) / J&J
    Amivantamab Plus Lazertinib vs Osimertinib in First-line EGFR -mutant Advanced NSCLC: Longer Follow-up of the MARIPOSA Study (20D) -  Aug 11, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_2743;    
    P3
    At 24 months, 75% and 70% of patients were alive in the amivantamab-lazertinib and osimertinib arms, respectively; corresponding values at 36 months were 61% and 53%. Conclusions : Amivantamab-lazertinib continues to show a trend towards improved OS while also improving post-progression outcomes vs osimertinib, reaffirming amivantamab-lazertinib as a first-line standard-of-care for EGFR -mutated advanced NSCLC.
  • ||||||||||  Preclinical, Journal:  Potential Utility of a 4th-Generation EGFR-TKI and Exploration of Resistance Mechanisms-An In Vitro Study. (Pubmed Central) -  Jul 27, 2024   
    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.
  • ||||||||||  Rybrevant (amivantamab-vmjw) / J&J, Lazcluze (lazertinib) / J&J
    Enhanced vs Standard Dermatologic Management with Amivantamab-Lazertinib in Advanced NSCLC: Phase 2 COCOON Study (Exhibit Hall) -  Jul 24, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_2517;    
    P2
    Planned enrollment is 180 patients, which is estimated to provide a power of 90% with a 2-sided alpha of 0.05 to detect a treatment difference between arms A and B in the incidence of grade ?2 dermatologic AEs. Safety will be assessed throughout the study by AE frequency and severity.
  • ||||||||||  What is the Optimal First-Line Regimen for EGFR-Mutated Advanced Non-Small Cell Lung Cancer: A Network Meta-Analysis (Exhibit Hall) -  Jul 24, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_2118;    
    Compared with other interventions, combination therapies based on third-generation TKIs, especially osimertinib plus ramucirumab (OSI_RAM), showed the most favorable PFS prolongation in overall patients (Figure A)...In terms of overall survival, despite the combination regimens based on third-generation TKIs also showing relatively superior outcomes, erlotinib plus chemotherapy and gefitinib plus chemotherapy were ranked more favorably (Figure B)...Conclusions : Combination regimens based on third-generation TKIs, especially OSI_RAM, showed superior efficacy compared with third-generation TKIs monotherapy or other regimens as first-line therapy in EGFR-mutated advanced NSCLC, along with an acceptable safety profile. Our study concluded that combination regimens based on third-generation TKIs (OSI_RAM, OSI plus chemotherapy, OSI plus bevacizumab, amivantamab plus lazertinib and aumolertinib plus apatinib) could be the new and clinically preferable first-line, standard of care for EGFR-mutated advanced NSCLC.