New Directions and Approaches in the Management of HER2-Altered Non-Small Cell Lung Cancer — Issue 1

Faculty

Faculty

Mark Jeng

MD, PhD

Memorial Sloan Kettering Cancer Center, New York, New York

Medical Oncology Fellow

Faculty

Joshua K Sabari

MD

NYU Langone Health, Perlmutter Cancer Center, New York, New York

Attending Physician, Thoracic Medical Oncology, Assistant Professor of Medicine

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

• Appreciate the incidence and clinical relevance of human epidermal growth factor receptor 2 (HER2) mutations and protein overexpression in non-small cell lung cancer (NSCLC), and consider the implications for biomarker assessment and current clinical management.
• Evaluate published research findings along with patient clinicopathologic variables to individualize the selection and sequencing of therapy for patients with HER2-mutant NSCLC.
• Recognize the spectrum, frequency, and severity of toxicities associated with HER2-targeted tyrosine kinase inhibitors and antibody-drug conjugates with established activity in lung cancer in order to facilitate the safe and effective use of these agents.

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 enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of this CME activity, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 0.75 Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, this program has been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
Successful completion of this CME activity, which includes participation in the evaluation component and a post-test, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, this program has been specifically designed for the following ABS practice area: complex general surgical oncology.

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.

HOW TO USE THIS CME ACTIVITY
To receive credit for this activity, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better, and fill out the evaluation.

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 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 — Dr Jeng has no relevant financial relationships to disclose. The following faculty reported relevant financial relationships with ineligible entities:

Dr Sabari — Advisory Committees and Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, EMD Serono Inc, Genentech, a member of the Roche Group, Janssen Biotech Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Mirati Therapeutics Inc, Pfizer Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines Inc, Sanofi, Takeda Pharmaceuticals USA Inc; Contracted Research: Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Janssen Biotech Inc, Johnson & Johnson, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Mirati Therapeutics Inc, Regeneron Pharmaceuticals Inc.

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, Catalyst Pharmaceuticals Inc, 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, Tesaro, A GSK Company, and Verastem Inc.

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.

This educational activity contains 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 publisher or grantor.

This activity is supported by an educational grant from Boehringer Ingelheim Pharmaceuticals Inc.

Release date: July 2026
Expiration date: July 2027

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Heymach J et al. Circulating tumor DNA (ctDNA) analysis following zongertinib treatment (tx) in patients (pts) with human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC): Phase Ia/Ib Beamion LUNG-1 study. ESMO 2025;Abstract 2020P.

Heymach JV et al. Zongertinib in previously treated HER2 mutant non-small cell lung cancer. N Engl J Med 2025;392(23):2321-33. Abstract

Jänne PA et al. Final analysis results and patient-reported outcomes from DESTINY Lung02 — A dose-blinded, randomized, phase 2 study of trastuzumab deruxtecan in patients with HER2-mutant metastatic NSCLC. J Thorac Oncol 2025;20(12):1814-28. Abstract

Jänne PA et al. Trastuzumab deruxtecan for ERBB2-mutant metastatic NSCLC with or without brain metastases. JAMA Netw Open 2025;8(11). Abstract

Johnson ML et al. Beamion LUNG-2: A Phase III randomized controlled trial of zongertinib (BI 1810631) versus standard of care in patients with locally advanced/metastatic non-squamous non-small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain (TKD) mutations. ASCO 2024;Abstract TPS8654.

Le X et al. Sevabertinib in advanced HER2 mutant non-small cell lung cancer. N Engl J Med 2025;393(18):1819-32. Abstract

Le X et al. SOHO-02: Phase III trial of BAY 2927088 in patients with locally advanced or metastatic NSCLC with HER2-activating mutations. ASCO 2025;Abstract TPS8648.

Li BT et al. Open-label, randomized, multicenter, phase 3 study evaluating trastuzumab deruxtecan (T-DXd) as first-line treatment in patients with unresectable, locally advanced, or metastatic non–small cell lung cancer (NSCLC) harboring HER2 exon 19 or 20 mutations (DESTINY-Lung04). ASCO 2022;Abstract TPS9137.

Popat S et al. Zongertinib as first-line treatment in patients with advanced HER2-mutant NSCLC: Beamion LUNG 1. ESMO 2025;Abstract LBA74.

Schram AM et al. Beamion PANTUMOR-1: Rationale and design of a phase II trial of zongertinib in HER2-overexpressed/amplified or HER2-mutant solid tumors. Future Oncol 2026;22(7):795-803. Abstract