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ASCO 2025 | HERTHENA-Lung02: patritumab deruxtecan in pretreated EGFRm-NSCLC
Tony Mok, MD, Chinese University of Hong Kong, Hong Kong, China, discusses the Phase III HERTHENA-Lung02 trial (NCT05338970) of patritumab deruxtecan (HER3-DXd) versus platinum-based chemotherapy in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) following progression on third-generation EGFR tyrosine kinase inhibitors. HER3-DXd significantly improved progression-free survival and showed intracranial activity in patients with brain metastases. The safety profile was consistent with previous studies, with hematologic and gastrointestinal events being most common. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
The HERTHENA-Lung02 study is a randomized Phase III study comparing a HER3-DXd which is an ADC against HER3 versus a standard chemotherapy for patients who had resistance to standard third-line, first-generation EGFR TKI after oral treatment. So there are two types, is either the patient who took the EGFR third generation as a first-line therapy, or it can be as a second-line therapy after they failed their first generation T790M positive and go on third generation...
The HERTHENA-Lung02 study is a randomized Phase III study comparing a HER3-DXd which is an ADC against HER3 versus a standard chemotherapy for patients who had resistance to standard third-line, first-generation EGFR TKI after oral treatment. So there are two types, is either the patient who took the EGFR third generation as a first-line therapy, or it can be as a second-line therapy after they failed their first generation T790M positive and go on third generation. Randomized head-to-head, total of 563 patients, and randomized with the primary endpoint of looking at the Burke progression-free survival, and for which we do have a positive outcome of a hazard ratio of 0.74. However, the median is actually very close, 5.6 versus 5.4 months. In the response rate, there is actually improved response rate by approximately 10%. However, the overall survival is negative. There is actually a hazard ratio of 0.94, no different in the overall survival. Toxicity-wise, there’s actually a slightly higher GI and hematological toxicity. So that has to be adjusted with some support, but it’s a manageable situation. So overall, we do have an improvement in response rate, improvement in progression-free survival, but no difference in overall survival.
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Disclosures
Employment – The Chinese University of Hong Kong
Leadership – AstraZeneca; Aurora Tele-Oncology Platform; HUTCHMED; Insighta Holdings Limited
Stock and Other Ownership Interests – Alentis Therapeutics; AstraZeneca; Aurora Tele-Oncology Platform; Biolidics; D3 Bio; HUTCHMED; Lunit; Prenetics
Honoraria – Abbvie; ACEA Pharmaceutical Research; Adagene; Alpha Biopharma; Amgen; Amoy Diagnostics; AnHeart Therapeutics; AstraZeneca; AVEO; BeiGene; Berry Oncology; Blueprint Medicines; Boehringer Ingelheim; Bristol-Myers Squibb; C4 Therapeutics; CStone Pharmaceuticals; Curio Science; D3; Da Volterra; Daiichi Sankyo/UCB Japan; Daz Group; Eisai; Fishawack Facilitate; Gilead Sciences; GLG’s Healthcare; Gritstone Bio; Guardant Health; Hengrui Therapeutics; Ignyta; Illumina; Incyte; Inivata; InMed; IQVIA; Janssen; Jiahui Holdings Co; Lakeshore Biotechnology; Lilly; Lucence; Lucence; MD Health Brazil,; Medscape; Merck; Merck Sharp & Dohme; MiRXES; Novartis; Novocure; Omega Therapeutics; Origimed; PeerVoice; Permanyer Publications; Pfizer; Physicans’ Education Resource; Prenetics; Prime Oncology; Qiming Development (HK) Ltd.; Regeneron; Research to Practice; Roche; Sanofi Aventis GmbH; SFJ Pharmaceutical Ltd; Shanghai BeBirds Translation & Consulting; Shanghai Promedican Pharmaceuticals Co., Ltd; Simcere of America Inc.; Summit Therapeutics Sub, Inc.; Suzhou Liangyihui Network Technology; Synergy Research; Taiho Pharmaceutical; Takeda; Tigermed; touchIME; Vertex; Virtus Medical Group; Xencor; Yuhan
Consulting or Advisory Role – Abbvie; ACEA Pharmaceutical Research; Adagene; Alpha Biopharma; Amgen; Amoy Diagnostics; AstraZeneca; Bayer HealthCare Pharmacuticals; BeiGene; BerGenBio; Berry Oncology; Blueprint Medicines; Boehringer Ingelheim; Bowtie Life Insurance Company; Bridgebio; Bristol-Myers Squibb; C4 Therapeutics; Cirina; Covidien/Medtronic; Covidien/Medtronic; CStone Pharmaceuticals; Curio Science; D3; Da Volterra; Daiichi Sankyo/UCB Japan; Eisai; Elevation Oncology; Fishawack Facilitate; G1 Therapeutics; geneDecode; Genentech; Gilead Sciences; Gritstone Bio; Guardant Health; Hengrui Therapeutics; HUTCHMED; Ignyta; Imagene AI Ltd.; Incyte; Inivata; IQvia; Janssen; Lakeshore Biotechnology; Lilly; Loxo; Lucence; Lunit; Medtronic; Merck Serono; Merck Sharp & Dohme; Mirati Therapeutics; MiRXES; Novartis; Omega Therapeutics; OrigiMed; OSE Immunotherapeutics; Pfizer; Prenetics; PrIME Oncology; Puma Biotechnology; Qiming Development (HK) Ltd.; Regeneron; Roche; SFJ Pharmaceuticals Group; Simcere; Summit Therapeutics; Synergy Research; Takeda; Tigermed; Vertex; Virtus Medical Group; Yuhan
Research Funding – AstraZeneca (Inst); Boehringer Ingelheim (Inst); Bristol-Myers Squibb (Inst); G1 Therapeutics (Inst); Merck Serono (Inst); Merck Sharp & Dohme (Inst); Novartis (Inst); Pfizer (Inst); Roche (Inst); SFJ Pharmaceuticals Group (Inst); Takeda (Inst); Xcovery (Inst)
Travel, Accommodations, Expenses – Abbvie; Astrazeneca; Daiichi Sankyo; Liangyihui; MiRXES; Novartis; Pfizer; Pfizer; Roche; Zai Lab
