Cases from the Community: Investigators Discuss the Optimal Management of EGFR-Mutated Non-Small Cell Lung Cancer

Faculty

Faculty

Sarah B Goldberg

MD, MPH

Yale Cancer Center New Haven, Connecticut

Professor of Medicine (Medical Oncology) Chief of Thoracic Oncology

Faculty

Jonathan Goldman

MD

UCLA Hematology and Oncology, Santa Monica, California

Professor of Medicine

UCLA Health, Santa Monica, California

Director of Clinical Trials in Thoracic Oncology, Associate Director of Drug Development

Faculty

Joel W Neal

MD, PhD

Stanford University School of Medicine, Stanford, California

Professor of Medicine, Division of Oncology

Stanford Cancer Institute, Stanford, California

Medical Director, Cancer Clinical Trials Office

Stanford Medicine Cancer Center, Stanford, California

Medical Director, Informatics Technology

Faculty

Antonio Passaro

MD, PhD

Division of Thoracic Oncology European Institute of Oncology Milan, Italy

Director

Moderator

Jacob Sands

MD

Dana-Farber Cancer Institute, Boston, Massachusetts

Associate Chief, Thoracic Oncology

Harvard Medical School, Boston, Massachusetts

Assistant Professor

Program Schedule — Central Time
6:00 PM – 6:30 PM — Registration and Dinner
6:30 PM – 8:30 PM — Educational Meeting

MODULE 1: Evolving First-Line Treatment for Metastatic EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC)

• Long-term outcomes observed with up-front osimertinib monotherapy for patients with metastatic EGFR-mutated NSCLC
• Major efficacy and safety findings, including outcomes from the final overall survival (OS) analysis, from the Phase III FLAURA2 trial of osimertinib combined with chemotherapy versus osimertinib alone as first-line treatment for EGFR-mutant NSCLC
• Extended follow-up, including published OS findings, from the Phase III MARIPOSA trial of up-front treatment with amivantamab/lazertinib or lazertinib alone versus osimertinib for patients with metastatic EGFR-mutant NSCLC
• Documented CNS activity of osimertinib/chemotherapy and amivantamab/lazertinib in EGFR-mutated advanced NSCLC
• Optimal selection of patients with newly diagnosed EGFR-mutated NSCLC to receive osimertinib/chemotherapy and amivantamab/lazertinib

MODULE 2: EGFR-Targeted Therapeutic Strategies for Relapsed EGFR-Mutant NSCLC

• Key data from the Phase III MARIPOSA-2 study supporting the FDA approval of amivantamab in combination with platinum-based chemotherapy for patients with progressive EGFR-mutated advanced NSCLC
• Optimal incorporation of amivantamab/chemotherapy into current management algorithms
• Efficacy and safety outcomes documented with a subcutaneous formulation of amivantamab in combination with lazertinib in refractory and treatment-naïve EGFR-mutated advanced NSCLC
• Early data with and ongoing studies combining osimertinib with other systemic therapies in order to overcome common mechanisms of resistance
• Preliminary data with and ongoing evaluation of other EGFR-targeted agents/strategies (eg, next-generation EGFR tyrosine kinase inhibitors [TKIs], izalontamab brengitecan [iza-bren]) for relapsed EGFR-mutant NSCLC

MODULE 3: Utility of TROP2-Targeted Antibody-Drug Conjugates (ADCs) in the Management of EGFR-Mutant NSCLC

• Mechanism of antitumor activity of datopotamab deruxtecan (Dato-DXd) and rationale for its investigation in pretreated EGFR-mutant NSCLC
• Antitumor activity observed with Dato-DXd in patients with previously treated EGFR-mutated NSCLC in a pooled analysis of the TROPION-Lung05 and TROPION-Lung01 trials
• Recent FDA approval of Dato-DXd for EGFR-mutated NSCLC after prior EGFR-directed therapy and platinum-based chemotherapy; current role of this strategy in treatment
• Intracranial activity of Dato-DXd in patients with NSCLC and brain metastases; implications for its utility in pretreated EGFR-mutant disease
• Published data with and ongoing evaluation of other TROP2-targeted ADCs (eg, sacituzumab tirumotecan) for EGFR TKI-resistant, EGFR-mutated advanced NSCLC

MODULE 4: Emerging Role of Bispecific Antibody-Based Approaches in the Treatment of EGFR-Mutated NSCLC

• Available data with and current role, if any, of immune checkpoint inhibitors in therapy for patients with NSCLC and EGFR mutations
• Mechanism of antitumor activity of the PD-1 x VEGF bispecific antibody ivonescimab; rationale for its investigation in pretreated EGFR-mutant NSCLC
• Design, eligibility criteria, and efficacy and safety findings from the Phase III HARMONi trial evaluating ivonescimab in combination with carboplatin and pemetrexed for patients with EGFR-mutated NSCLC after disease progression on a third-generation TKI
• Recent acceptance of a biologics license application for ivonescimab/chemotherapy for pretreated EGFR-mutated NSCLC; potential role in clinical practice
• Structural components and mechanism of action of the first-in-class bispecific ADC iza-bren
• Available research data (eg, BL-B01D1-101, BL-B01D1-203, BL-B01D1-LUNG-101) with and ongoing evaluation of iza-bren for patients with NSCLC harboring EGFR mutations

MODULE 5: Tolerability Considerations with Available and Emerging Therapies for NSCLC with EGFR Mutations

• Comparative tolerability profiles of osimertinib/chemotherapy and amivantamab/lazertinib; implications for the selection of first-line therapy for EGFR-mutant metastatic NSCLC
• Optimal approach to preventing infusion-related reactions with amivantamab; relevant findings from the Phase II SKIPPirr study
• Results from the Phase II COCOON study evaluating the impact of enhanced versus standard dermatologic management on the incidence of dermatologic adverse events (AEs) for patients with EGFR-mutated metastatic NSCLC who receive first-line amivantamab/lazertinib
• Spectrum, frequency and severity of toxicities reported with Dato-DXd for patients with EGFR-mutant advanced NSCLC
• Recommended algorithms for monitoring for, mitigating and managing common and more serious AEs documented with Dato-DXd
• Spectrum, frequency, severity and management of toxicities associated with sunvozertinib and zipalertinib
• Frequency, severity and management of toxicities associated with ivonescimab

Target Audience
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of lung cancer.

Learning Objectives
Upon completion of this activity, participants should be able to 

• Counsel patients with newly diagnosed metastatic EGFR-mutated non-small cell lung cancer (NSCLC) regarding available therapeutic considerations, explaining the relevance of mutation type, symptomatology, sites and extent of metastases, prior therapeutic exposure and other factors.
• Appreciate the biological rationale for dual inhibition of MET and EGFR in patients with EGFR-mutated NSCLC, and understand recently presented data establishing the benefit of this strategy.
• Evaluate the documented efficacy of chemotherapy combined with EGFR-targeted therapy, and consider the current role of available approaches in both the front-line and relapsed/refractory settings for patients with metastatic NSCLC and EGFR mutations.
• Review published research findings with TROP2-directed antibody-drug conjugates for patients with metastatic NSCLC and EGFR mutations, and optimally incorporate these agents into treatment algorithms.
• Understand the biology of EGFR exon 20 insertion mutations, and evaluate how available therapies should be administered to patients with these abnormalities.
• Appraise the scientific rationale for the development of bispecific antibodies directed at PD-1 x VEGF, and reflect on the potential role of these agents in the management of EGFR-mutated NSCLC.
• Recall the biological rationale for the evaluation of various novel therapeutic approaches for patients with NSCLC and EGFR mutations.

CME Credit Form
A CME credit link will be given to each participant as part of the meeting course materials.

Accreditation Statement
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation Statement
Research To Practice designates this live activity for a maximum of 2 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Privacy Policy
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

Unlabeled/Unapproved Uses Notice
This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the provider or grantors.

Content Validation and Disclosures
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships will have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations. 

FACULTY — Prof Passaro has no relevant financial relationships to disclose. The following faculty reported relevant financial relationships with ineligible entities:

Dr Goldberg — Advisory Committees: AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BlossomHill Therapeutics, Daiichi Sankyo Inc, Johnson & Johnson, Lilly, Merck, Regeneron Pharmaceuticals Inc, Summit Therapeutics, Synthekine, Tubulis; Contracted Research: Adela, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals Inc, Mirati Therapeutics Inc; Data and Safety Monitoring Boards/Committees: Daiichi Sankyo Inc. Dr Goldman — Consulting Agreements: AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Genentech, a member of the Roche Group, Janssen Biotech Inc, Lilly, Pfizer Inc, Summit Therapeutics; Contracted Research: AbbVie Inc, Agenus Inc, Amgen Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Genentech, a member of the Roche Group, GSK , Janssen Biotech Inc, Lilly, Merck, Pfizer Inc, Puma Biotechnology Inc, RayzeBio, Summit Therapeutics, Tango Therapeutics. Dr Neal — Advisory Committees (Consulting or Advisory Roles): AbbVie Inc, Amgen Inc, Anheart Therapeutics, AstraZeneca Pharmaceuticals LP, Blueprint Medicines, Bristol Myers Squibb, D2G Oncology Inc, Daiichi Sankyo Inc, Exelixis Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Iovance Biotherapeutics, Janssen Biotech Inc, Lilly, Mirati Therapeutics Inc, Natera Inc, Novartis, Novocure Inc, Nuvation Bio Inc, Regeneron Pharmaceuticals Inc, Sanofi, Summit Therapeutics, Surface Oncology, Takeda Pharmaceuticals USA Inc, Turning Point Therapeutics Inc; Contracted Research: Adaptimmune, Boehringer Ingelheim Pharmaceuticals Inc, Exelixis Inc, Genentech, a member of the Roche Group, GSK, Janssen Biotech Inc, Merck, Nektar Therapeutics, Novartis, Nuvalent, Revolution Medicines, Takeda Pharmaceuticals USA Inc.

MODERATOR
Dr Sands — Consulting Agreements: AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Catalyst Pharmaceuticals Inc, Daiichi Sankyo Inc, Fosun Pharma, Genentech, a member of the Roche Group, Gilead Sciences Inc, GSK, Lilly, Merck, Novartis, Pfizer Inc, PharmaMar, Sanofi; Contracted Research: Amgen Inc, Novartis.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Nuvation Bio Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Summit Therapeutics, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS
Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

Supporters
This activity is supported by educational grants from AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, and Johnson & Johnson.

Hilton Chicago
720 South Michigan Avenue
Chicago, IL 60605
Phone: (312) 922-4400

Meeting Room
Continental Room A (Lobby Level)

Directions
The Hilton Chicago hotel is located just 5 minutes (2.5 miles) north of the McCormick Place convention center, where the ASCO Annual Meeting is taking place.