Clinical Investigators Provide Perspectives on the Current and Future Clinical Care of Patients with EGFR Mutation-Positive Non-Small Cell Lung Cancer — Symposium Video Proceedings

Faculty

TARGET AUDIENCE
This program is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of lung cancer.

LEARNING OBJECTIVES

• Acknowledge available clinical trial findings with EGFR tyrosine kinase inhibitors for nonmetastatic EGFR mutation-positive non-small cell lung cancer (NSCLC), and identify patients for whom treatment with this novel approach would be warranted.
• Counsel patients with newly diagnosed metastatic EGFR mutation-positive NSCLC regarding available therapies, 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 mutation-positive NSCLC, and understand recently presented data establishing the benefit of this strategy.
• Evaluate the documented efficacy of chemotherapy combined with EGFR-targeted therapy for patients with EGFR mutation-positive metastatic NSCLC, and consider the current role of available approaches in both the front-line and relapsed/refractory settings.
• Consider the scientific justification for targeting HER3 in patients with EGFR mutation-positive NSCLC, and review the structural components, mechanism of action and available research with novel HER3-directed antibody-drug conjugates (ADCs).
• Review published research findings with TROP2-directed ADCs for EGFR mutation-positive metastatic NSCLC, and consider the potential clinical role of this strategy.
• Understand the biology of EGFR exon 20 insertion mutations, and evaluate how currently available therapies should be used in the care of patients with these alterations.
• Recall the biological rationale for and the design of ongoing clinical trials evaluating novel therapeutic approaches for patients with EGFR mutation-positive NSCLC.

ACCREDITATION STATEMENT
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CREDIT DESIGNATION STATEMENT
Video Program: Research To Practice designates this enduring material for a maximum of 2.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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Successful completion of these CME activities, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 2.25 (video) 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 each 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, these programs have been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINOUS CERTIFICATION (CC)
Successful completion of these CME activities, 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, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

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HOW TO USE THIS CME ACTIVITY
Video Program: This CME activity consists of a video component. To receive credit, 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 located at ResearchToPractice.com/ASCO2025/EGFRNSCLC/Video/CME.

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 — The following faculty reported relevant financial relationships with ineligible entities:

Nicolas Girard, MD, PhD
Head of Medical Oncology, Institut Curie
Full Professor
UVSQ, Paris-Saclay University
Paris, France

Advisory Committees: AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Baxter International Inc, Bristol Myers Squibb, Daiichi Sankyo Inc, Gilead Sciences Inc, Janssen Biotech Inc, LEO Pharma, Lilly, MSD, Pfizer Inc, Pierre Fabre, Sanofi, Suven Pharma, Takeda Pharmaceutical Company Limited; Contracted Research (Through Institution): AstraZeneca Pharmaceuticals LP, MSD; Data and Safety Monitoring Boards/Committees: Roche Laboratories Inc; Speakers Bureaus: AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Daiichi Sankyo Inc, Janssen Biotech Inc, MSD, Sanofi; Nonrelevant Financial Relationships: Clinical Care Options, PeerVoice.

Jonathan Goldman, MD
Professor of Medicine, UCLA Hematology and Oncology
Director of Clinical Trials in Thoracic Oncology
Associate Director of Drug Development
UCLA Health
Santa Monica, California

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 Inc, Summit Therapeutics, Tango Therapeutics.

Pasi A Jänne, MD, PhD, FASCO
Senior Vice President for Translational Medicine
Lowe Center for Thoracic Oncology
Professor of Medicine
Harvard Medical School
David M Livingston, MD, Chair
Director, Robert and Renée Belfer Center for Applied Cancer Science
Director, Chen-Huang Center for EGFR-Mutant Lung Cancers
Dana-Farber Cancer Institute
Boston, Massachusetts

Advisory Committees: AbbVie Inc, Accutar Biotechnology Inc, Allorion Therapeutics, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Biocartis, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Chugai Pharmaceutical Co Ltd, Daiichi Sankyo Inc, Dizal Pharma, Duality Biologics, Eisai Inc, Frontier Medicines, Genentech, a member of the Roche Group, GSK, Hongyun Biotechnology, Lilly, Merus, Mirati Therapeutics Inc, Monte Rosa Therapeutics, Myris Therapeutics, Novartis, Nuvalent, Pfizer Inc, Roivant, Sanofi, Scorpion Therapeutics, SFJ Pharmaceuticals, Syndax Pharmaceuticals, Takeda Pharmaceuticals USA Inc, TOLREMO, Transcenta, Voronoi; Contracted Research (All to Institution): AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals Inc, Daiichi Sankyo Inc, Lilly, Puma Biotechnology Inc, Revolution Medicines, Takeda Pharmaceuticals USA Inc; Royalties: Postmarketing royalties from Dana-Farber Cancer Institute-owned intellectual property on EGFR mutations licensed to Labcorp; Stock Options — Private Company: Frontier Medicines.

Suresh S Ramalingam, MD
Executive Director, Winship Cancer Institute
Roberto C Goizueta Chair for Cancer Research
Emory University School of Medicine
Atlanta, Georgia

Contracted Research (Research Support to Institution): Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Merck, Pfizer Inc; Data and Safety Monitoring Boards/Committees: Gilead Sciences Inc, Johnson & Johnson (no honorarium received).

Joshua K Sabari, MD
Attending Physician
Thoracic Medical Oncology
Assistant Professor of Medicine
NYU Langone Health
Perlmutter Cancer Center
New York, New York

Advisory Committees and Consulting Agreements (Advisory Boards/Consultant, Personal Fees): AbbVie Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, EMD Serono Inc, Genentech, a member of the Roche Group, Janssen Biotech Inc, Jazz Pharmaceuticals Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Mirati Therapeutics Inc, Pfizer Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines, Sanofi, Takeda Pharmaceuticals USA Inc; Contracted Research (Institutional): Bristol Myers Squibb, Janssen Biotech Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Mirati Therapeutics Inc, Regeneron Pharmaceuticals Inc.

MODERATOR
Helena Yu, MD
Medical Oncologist
Associate Attending
Memorial Sloan Kettering Cancer Center
New York, New York

Consulting Agreements: AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Black Diamond Therapeutics Inc, Bristol Myers Squibb, Cullinan Therapeutics, Daiichi Sankyo Inc, Ipsen Biopharmaceuticals Inc, Janssen Biotech Inc, Pfizer Inc, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc; Contracted Research (To Institution): AstraZeneca Pharmaceuticals LP, Black Diamond Therapeutics Inc, Cullinan Therapeutics, Daiichi Sankyo Inc, Janssen Biotech Inc, Kumquat Biosciences, SystImmune Inc, Taiho Oncology Inc; Data and Safety Monitoring Boards/Committees: Janssen Biotech Inc, Mythic Therapeutics.

SURVEY PARTICIPANTS
Shirish M Gadgeel, MD — Advisory Committees: AbbVie Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Merck, Nuvation Bio, Pfizer Inc, Takeda Pharmaceuticals USA Inc; Data and Safety Monitoring Boards/Committees: AstraZeneca Pharmaceuticals LP. Alexander I Spira, MD, PhD — Advisory Committees: Amgen Inc, ArriVent Biopharma, AstraZeneca Pharmaceuticals LP, Black Diamond Therapeutics Inc, Blueprint Medicines, Bristol Myers Squibb, Daiichi Sankyo Inc, Gritstone bio, Incyte Corporation, Janssen Biotech Inc, Jazz Pharmaceuticals Inc, Lilly, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Novartis, Regeneron Pharmaceuticals Inc, Sanofi, Takeda Pharmaceuticals USA Inc; Contracted Research: AbbVie Inc, ADC Therapeutics, AI Therapeutics, Alkermes, Amgen Inc, ArriVent Biopharma, Astellas, Astex Pharmaceuticals, AstraZeneca Pharmaceuticals LP, Black Diamond Therapeutics Inc, Blueprint Medicines, BluPrint Oncology, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, CytomX Therapeutics, Daiichi Sankyo Inc, Gritstone bio, Ignyta Inc, Incyte Corporation, Janssen Biotech Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, MacroGenics Inc, Medikine, Mersana Therapeutics Inc, Nalo Therapeutics, Novartis, Plexxikon Inc, Prelude Therapeutics, Regeneron Pharmaceuticals Inc, Revolution Medicines, Roche Laboratories Inc, Rubius Therapeutics, Scorpion Therapeutics, Synthekine, Takeda Pharmaceuticals USA Inc; Honoraria: AbbVie Inc, Amgen Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, CytomX Therapeutics, Janssen Biotech Inc, Merck, Novartis, Prelude Therapeutics, Takeda Pharmaceuticals USA 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.

These educational activities 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 publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Johnson & Johnson, and Taiho Oncology Inc.

Release date: June 2025
Expiration date: June 2026

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

Dr Yu

Cho BC et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med 2024;391(16):1486-98. Abstract

Felip E et al. 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;Abstract 8504.

Garassino MC et al. Osimertinib long-term tolerability in patients with EGFRm NSCLC enrolled in the AURA program or FLAURA study. WCLC 2022;Abstract EP08.02-108.

Janne P et al. Osimertinib with/without platinum-based chemotherapy as first-line treatment in patients with EGFRm advanced NSCLC (FLAURA2). WCLC 2023;Abstract PL03.13.

Passaro A et al. Amivantamab plus chemotherapy (with or without lazertinib) vs chemotherapy in EGFR-mutated advanced NSCLC after progression on osimertinib: MARIPOSA-2, a phase III, global, randomized, controlled trial. ESMO 2023;Abstract LBA15.

Planchard D et al. LAURA2: Safety and CNS outcomes of first-line (1L) osimertinib (osi) ± chemotherapy (CTx) in EGFRm advanced NSCLC. ESMO 2023;Abstract LBA68.

Planchard D et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med 2023;389(21):1935-48. Abstract

Popat S et al. Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutated, advanced non-small cell lung cancer after disease progression on osimertinib: Second interim overall survival from MARIPOSA-2. ESMO 2024;Abstract LBA54.

Ramalingam SS et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med 2020;382(1):41-50. Abstract

Soria J-C et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 2018;378(2):113-25. Abstract

Valdiviezo N et al. FLAURA2: Impact of tumor burden on outcomes of 1L osimertinib ± chemotherapy in patients with EGFR-mutated advanced NSCLC. ELCC 2024;Abstract MA12.04.

Watanabe K et al. The whole picture of first-line osimertinib for EGFR mutation-positive advanced NSCLC: Real-world efficacy, safety, progression pattern, and posttreatment therapy (Reiwa Study). JTO Clin Res Rep 2024;5(11):100720. Abstract

Yang JC-H et al. Amivantamab plus lazertinib vs osimertinib in first-line (1L) EGFR-mutant (EGFRm) advanced NSCLC: Final overall survival (OS) from the phase III MARIPOSA study. ELCC 2025;Abstract 4O.

 

Dr Sabari

Basse C et al. Management of cutaneous toxicities under amivantamab (anti MET and anti EGFR bispecific antibody) in patients with metastatic non-small cell lung cancer harboring EGFR Exon20ins: Towards a proactive, multidisciplinary approach. Lung Cancer 2022;173:116-23. Abstract

Girard N et al. Preventing moderate to severe dermatologic adverse events in first-line EGFR-mutant advanced NSCLC treated with amivantamab plus lazertinib: Early success of the COCOON trial. ELCC 2025;Abstract 10MO.

Kim TM et al. Tepotinib + osimertinib in EGFR-mutant NSCLC with MET amplification following 1L osimertinib: INSIGHT 2 primary analysis. WCLC 2023;Abstract OA21.05.

Leighl NB et al. Subcutaneous versus intravenous amivantamab, both in combination with lazertinib, in refractory epidermal growth factor receptor-mutated non-small cell lung cancer: Primary results from the phase III PALOMA-3 study. J Clin Oncol 2024;42(30):3593-605. Abstract

Lopes G et al. Preventing infusion-related reactions with intravenous amivantamab: Primary results from SKIPPirr, a phase 2 study. WCLC 2024;Abstract MA12.08.

Passaro A et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: Primary results from the phase III MARIPOSA-2 study. Ann Oncol 2024;35(1):77-90. Abstract

Popat S et al. Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutated, advanced non-small cell lung cancer after disease progression on osimertinib: Second interim overall survival from MARIPOSA-2. ESMO 2024;Abstract LBA54.

Yu HA et al. Biomarker-directed phase II platform study in patients with EGFR sensitizing mutation-positive advanced/metastatic non-small cell lung cancer whose disease has progressed on first-line osimertinib therapy (ORCHARD). Clin Lung Cancer 2021;22(6):601-6. Abstract

 

Dr Ramalingam

Ahn M-J et al. Efficacy and safety of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously-treated EGFR-mutated advanced non-small cell lung cancer (NSCLC): A pooled analysis of TROPION-Lung01 and TROPION-Lung05. ESMO 2024;Abstract LBA7.

Kuo P et al. Trop-2 expression in non–small cell lung cancer. PLoS One 2025;20(4). Abstract

Le X et al. Osimertinib (osi) + datopotamab deruxtecan (Dato-DXd) in patients (pts) with EGFR-mutated (EGFRm) advanced NSCLC (aNSCLC) whose disease progressed on first-line (1L) osi: ORCHARD. ELCC 2025;Abstract 1O.

Sands J et al. Datopotamab deruxtecan in advanced or metastatic non-small cell lung cancer with actionable genomic alterations: Results from the phase II TROPION-Lung05 study. J Clin Oncol 2025;43(10):1254-65. Abstract

Zhao S et al. Sacituzumab tirumotecan in advanced non-small-cell lung cancer with or without EGFR mutations: Phase 1/2 and phase 2 trials. Nat Med 2025;[Online ahead of print]. Abstract

 

Dr Goldman

Blakely CM et al. Neoadjuvant osimertinib for the treatment of stage I-IIIA epidermal growth factor receptor-mutated non-small cell lung cancer: A phase II multicenter study. J Clin Oncol 2024;42(26):3105-14. Abstract

Herbst RS et al. Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer. Nat Med 2025;[Online ahead of print]. Abstract

Herbst RS et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer: Updated results from the phase III randomized ADAURA trial. J Clin Oncol 2023;41(10):1830-40. Abstract

Kelly K et al. Adjuvant erlotinib versus placebo in patients with stage IB-IIIA non-small-cell lung cancer (RADIANT): A randomized, double-blind, phase III trial. J Clin Oncol 2015;33(34):4007-14. Abstract

Lu S et al. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med 2024;391(7):585-97. Abstract

Lv C et al. Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): A multicenter, single-arm, open-label phase 2b trial. Lung Cancer 2023;178:151-6. Abstract

Pennell NA et al. Economic impact of next-generation sequencing versus single-gene testing to detect genomic alterations in metastatic non-small-cell lung cancer using a decision analytic model. JCO Precis Oncol 2019;3:1-9. Abstract

Robinson CG et al. Phase 3 study of durvalumab with SBRT for unresected stage I/II, lymph-node negative NSCLC (PACIFIC-4/RTOG3515). ASCO 2023;Abstract TPS8607.

Tsuboi M et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med 2023;389(2):137-47. Abstract

Tsuboi M et al. Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA. Future Oncol 2021;17(31):4045-55. Abstract

Wu Y-L et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med 2020;383(18):1711-23. Abstract

Zhong W-Z et al. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC: Final overall survival analysis of CTONG1104 phase III trial. J Clin Oncol 2021;39(7):713-22. Abstract

 

Prof Girard

Doucet L et al. Efficacy and safety of sunvozertinib in prior platinum treated NSCLC patients with EGFR exon 20 insertion mutations: Primary analysis from the multinational WU-KONG1B pivotal study. ESMO 2024;Abstract 1260P.

Felip E et al. Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR exon 20 insertion-mutated advanced NSCLC: Analysis of post-progression endpoints from PAPILLON. ELCC 2024;Abstract 2MO.

Garrido Lopez P et al. Long-term efficacy, safety, and predictors of response to amivantamab among patients with post-platinum EGFR Ex20ins-mutated advanced NSCLC. ELCC 2023;Abstract 30.

Girard N et al. Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC): Primary results from PAPILLON, a randomized phase III global study. ESMO 2023;Abstract LBA5.

Han B et al. A phase 1b study of furmonertinib, an oral, brain penetrant, selective EGFR Inhibitor, in patients with advanced NSCLC with EGFR exon 20 insertions. WCLC 2023;Abstract OA03.04.

Park K et al. Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy: Initial results from the CHRYSALIS phase I study. J Clin Oncol 2021;39(30):3391-402. Abstract

Piotrowska Z et al. Safety, tolerability, and antitumor activity of zipalertinib among patients with non-small-cell lung cancer harboring epidermal growth factor receptor exon 20 insertions. J Clin Oncol 2023;41(26):4218-25. Abstract

 

Dr Jänne

Haikala HM et al. EGFR inhibition enhances the cellular uptake and antitumor-activity of the HER3 antibody-drug conjugate HER3-DXd. Cancer Res 2022;82(1):130-41. Abstract

Hayashi H et al. Patritumab deruxtecan (HER3-DXd) in previously treated patients (pts) with advanced EGFR-mutated (EGFRm) NSCLC: Updated safety results from HERTHENA-Lung01. ELCC 2024;Abstract 11P.

Jänne PA et al. Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor–resistant, EGFR-mutated non–small cell lung cancer. Cancer Discov 2022;12(1):74-89. Abstract

Yu HA et al. Patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC following EGFRTKI and platinum-based chemotherapy: HERTHENA-Lung01. WCLC 2023;Abstract OA05.03.

Zhang L et al. BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic solid tumor: Results from a first-in-human phase 1 study. ASCO 2023;Abstract 3001.