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. 2025 Oct;21(25):3283-3292.
doi: 10.1080/14796694.2025.2561539. Epub 2025 Oct 14.

HERTHENA-PanTumor01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated advanced solid tumors

Thomas Powles  1 , Aarti Bhatia  2 , Barbara Burtness  2 , Takahiro Kogawa  3 , Tomohiro Nishina  4 , Izuma Nakayama  5 , Christos Fountzilas  6 , Dani R Castillo  7 , Meredith McKean  8 , Funda Meric-Bernstam  9 , Nicoletta Colombo  10 , James W Smithy  11 , Jérome Fayette  12 , Sunandana Chandra  13 , David W Sternberg  14 , Fan Jin  15 , Kendall Sullivan  16 , Sue Yueh  17 , Graham Clinthorne  18 , Ariel E Aguilo  19 , Ragini Kudchadkar  17 , Hidetoshi Hayashi  20
Affiliations

HERTHENA-PanTumor01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated advanced solid tumors

Thomas Powles et al. Future Oncol. 2025 Oct.

Abstract

Human epidermal growth factor receptor 3 (HER3) is a receptor tyrosine kinase that is expressed in numerous solid tumors. Higher levels of HER3 expression in multiple tumor types are associated with adverse clinical outcomes, such as reduced survival. However, there is currently no HER3-directed antibody-drug conjugate approved for the treatment of any cancer. Improved treatment options are needed, in particular for patients who progress on standard therapies. HER3-DXd is an investigational HER3-directed antibody-drug conjugate composed of an anti-HER3 monoclonal antibody linked to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. In previous clinical trials, HER3-DXd demonstrated a manageable safety profile and durable efficacy in previously treated, advanced EGFR-mutated NSCLC and advanced breast cancer across a range of baseline tumor HER3 expression levels. HER3-DXd has also shown preclinical antitumor efficacy in HER3-expressing cancers including cutaneous melanoma, gastric cancer, and prostate cancer, among others. The aim of this global phase II HERTHENA-PanTumor01 multicohort study is to assess the efficacy and safety of HER3-DXd in patients with relapsed or refractory locally advanced or metastatic solid tumors including melanoma, head and neck squamous cell, gastric/gastroesophageal junction, ovarian, cervical, endometrial, bladder, esophageal squamous cell, pancreatic, and prostate cancers.Clinical trial registration: NCT06172478 (ClinicalTrials.gov); 2023-507641-29-00 (EudraCT); jRCT2031230575 (Japan Registry of Clinical Trials).

Keywords: ADC; Gastric cancer; HER3; HER3-DXd; bladder cancer; esophageal cancer; gynecologic cancers; head and neck carcinoma; melanoma; pancreatic cancer; prostate cancer.

Plain language summary

Effective and tolerable treatment options are needed for patients with advanced cancer that stops responding to standard therapy. Human epidermal growth factor receptor 3, or HER3, is a protein that is found on the surface of tumor cells in many types of cancer. However, there is currently no approved treatment that targets only HER3. Patritumab deruxtecan (also called HER3‑DXd) is a type of targeted cancer drug called an antibody-drug conjugate, or ADC. It consists of a specially designed antibody (patritumab) linked to a chemotherapy drug (deruxtecan). The antibody in HER3-DXd attaches to HER3 on the surface of a tumor cell and then moves inside the cancer cell, where the chemotherapy is released, killing the cell. This article describes a clinical study called HERTHENA-PanTumor01 that is evaluating HER3-DXd in patients with cancer that stopped responding to standard therapy. All participants will have cancer that cannot be removed by surgery (unresectable), and in some cases has spread (metastatic). The study will enroll patients with different types of cancer, including skin, head and neck, stomach, ovarian, cervical, endometrial, bladder, esophageal, pancreatic, and prostate cancer. HERTHENA-PanTumor01 is an open-label study, meaning the doctor and the participant will know what treatment is being given. All study participants will receive HER3-DXd every 3 weeks through an IV infusion. HERTHENA-PanTumor01 will help doctors know more about how well HER3-DXd can shrink a patient’s tumor, and the side effects patients have while being treated. Currently, HER3-DXd is an investigational treatment, and doctors are not able to prescribe it.

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Conflict of interest statement

T. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seagen, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for The Uromigos podcast: Mashup Ltd; Financial Interests, Institutional, Other, Honoraria: Gilead; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Ipsen, Merck, MSD, Seagen, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai; Financial Interests, Institutional, Other, Honoraria: Gilead.

A. Bhatia: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Coherus, Regeneron, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Merck, PeerView, Medscape; Financial Interests, Personal, Writing Engagement: Clinical Care Options; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Personal and Institutional, Coordinating PI: Boehringer Ingelheim, Genentech; Non-Financial Interests, PI: Janssen.

B. Burtness: Financial Interests, Personal, Advisory Board: GSK, Merck, Merck KGaA, ALX Oncology, IO Biotech, Cue Biopharma, Seagen, Coherus, Janssen, Arnold and Porter, Rakuten, AstraZeneca, Merus; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Personal and Institutional, Coordinating PI: IO Biotech, GSK; Financial Interests, Personal and Institutional, Local PI: Merck, Cue Biopharma, Seagen; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo; Non-Financial Interests, Institutional, Proprietary Information: Merck; Non-Financial Interests, Institutional, Product Samples: VITRAC Therapeutics.

T. Kogawa: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Pfizer; Financial Interests, Institutional, Research Grant: Eli Lilly, Daiichi Sankyo.

T. Nishina: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, Ono Pharmaceutical, Bristol Myers Squibb, Astellas.

I. Nakayama: Financial Interests, Institutional, Local PI: Chugai Pharmaceutical, Daiichi Sankyo, MSD.

C. Fountzilas: Financial Interests, Institutional, Research Grant: Pfizer, Taiho Oncology, MSD; Financial Interests, Institutional, Local PI: Seagen, TransThera Sciences, AstraZeneca, Aravive, MSD, Kadmon, Astellas, Dragonfly Therapeutics, Rafael Pharmaceuticals, Ipsen, CG Pharmaceuticals, Biomea Fusion, Bellicum, Amgen, Legend Biotech; Non-Financial Interests, Institutional, Other, PI on clinical trial evaluating biomarker for treatment selection in pancreatic cancer: Valar Labs.

D.R. Castillo: Nothing to disclose.

M. McKean: Financial Interests, Institutional, Other, Consulting: Pfizer, Castle Biosciences, IQVIA, Merck, Moderna; Financial Interests, Institutional, Research Grant: Ascentage Pharma Group, Bicycle Therapeutics, Dragonfly Therapeutics, Epizyme, Exelixis, Genentech, GSK, Ideaya Biosciences, Ikena Oncology, Infinity Pharmaceuticals, Jacobio Pharmaceuticals, Moderna, NBE Therapeutics, Novartis, Oncorus, Plexxikon, Prelude Therapeutics, Regeneron, Sapience Therapeutics, Seagen, Tizona Therapeutics, Tmunity Therapeutics, TopAlliance Biosciences, Aadi Biosciences, Alpine Immune Sciences, Arcus Biosciences, Arvinas, American Society of Clinical Oncology (ASCO), Astellas, Bayer, BioMed Valley Discoveries, BioNTech, C4 Therapeutics, EMD Serono, Erasca, Foghorn Therapeutics, G1 Therapeutics, Gilead Sciences, ImmVira Pharma, Shanghai Kechow Pharma, Kezar Life Sciences, Kinnate Biopharma, MedImmune, Mereo BioPharma, Metabomed, Nektar, OncoC4, PACT Pharma, Pfizer, Poseida, Pyramid Biosciences, Scholar Rock, Synthrox, Takeda Pharmaceutical, Teneobio, Tempest Therapeutics, Xilio, Aulos Bioscience, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, IconOVir, Jazz Pharmaceuticals, Krystal Biotech, NucMito Pharmaceuticals, OnKure, Remix Therapeutics.

F. Meric-Bernstam: Financial Interests, Personal, Other, Consultant: AstraZeneca, OnCusp Therapeutics, Zymeworks; Financial Interests, Personal, Other, Consulting: Calibr, EcoR1, Exelixis, GT Aperion, Infinity Pharmaceuticals, Loxo Oncology, LegoChem Bio, Lengo Therapeutics, Tallac Therapeutics, Becton Dickinson, eFFECTOR Therapeutics, Jazz Pharmaceuticals; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Incyte, Karyopharm, Protai, TheraTechnologies, Zentalis, Parabilis Medicines, Harbinger Health, Mersana Therapeutics, Sanofi Pharmaceuticals; Financial Interests, Personal, Other, Consulting: Menarini Group; Financial Interests, Personal, Advisory Board/Consultant: Seagen; Financial Interests, Personal, Invited Speaker: Dava Oncology; Financial Interests, Institutional, Other, Local PI/Research Grant: Aileron Therapeutics, Bayer Healthcare, CytomX Therapeutics, Daiichi Sankyo, eFFECTOR Therapeutics, Taiho Pharmaceutical; Financial Interests, Institutional, Other, Local PI/Research Grant/Coordinating PI: AstraZeneca; Financial Interests, Institutional, Local PI: Calithera Biosciences, Curis Inc, Debiopharm International, Guardant Health, KLUS Pharma, Novartis, Jazz Pharmaceuticals, Zymeworks; Financial Interests, Institutional, Other, Local PI/Steering Committee Member: Genentech; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical, Puma Biotechnology, Repare; Other, Travel Support: European Organisation for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO); Other, Travel Support: Cholangiocarcinoma Foundation, Dava Oncology.

N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, AstraZeneca, MSD/Merck, Clovis Oncology, GSK, Immunogen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory Role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: OncXerna; Financial Interests, Personal, Invited Speaker: MSD/Merck; Financial Interests, Personal, Invited Speaker, Speaker: GSK; Financial Interests, Personal, Advisory Board: Novocure, BioNTech; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, GSK; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO (Alleanza contro il Tumore Ovarico).

J.W. Smithy: Financial Interests, Institutional, Coordinating PI: IO Biotech.

J. Fayette:Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Innate Pharma, Merck Serono, Roche, Pfizer, Hookipa; Non-Financial Interests, PI: AstraZeneca, MSD, Pfizer, Meru, Calliditas, ISA Pharmaceuticals.

S. Chandra: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, Pfizer, Regeneron; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Novartis, Regeneron, Pfizer, Merck; Financial Interests, Personal and Institutional, Steering Committee Member: Bristol Myers Squibb; Financial Interests, Other, Data Monitoring Committee Member: Alkermes.

D.W. Sternberg: Financial Interests, Personal, Full- or Part-Time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks or Ownership: Daiichi Sankyo.

F. Jin: Financial Interests, Personal, Full- or Part-Time Employment: Merck; Financial Interests, Personal, Stocks or Ownership: Merck.

K. Sullivan: Financial Interests, Personal, Full- or Part-Time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks or Ownership: Daiichi Sankyo.

S. Yueh: Financial Interests, Personal, Full- or Part-Time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks or Ownership: Daiichi Sankyo.

G. Clinthorne: Financial Interests, Personal, Full- or Part-Time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks or Ownership: Daiichi Sankyo.

A.E. Aguilo: Financial Interests, Personal, Full- or Part-Time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks or Ownership: Daiichi Sankyo.

R. Kudchadkar: Financial Interests, Personal, Full- or Part-Time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks or Ownership: Daiichi Sankyo.

H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bristol Myers Squibb, AstraZeneca K.K., Boehringer Ingelheim Japan, Chugai Pharmaceutical, Daiichi Sankyo K.K., Eli Lilly Japan K.K., Merck Biopharma, MSD K.K., Novartis Pharmaceuticals K.K., Pfizer, Takeda Pharmaceutical; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Eli Lilly Japan K.K., Pfizer, AstraZeneca K.K., Daiichi Sankyo; Financial Interests, Personal, Royalties: Sysmex; Financial Interests, Personal, Steering Committee Member: Janssen Pharmaceutical K.K., GSK, Daiichi Sankyo; Financial Interests, Institutional, Local PI: IQVIA Services Japan K.K., Syneos Health Clinical K.K., EPS Corporation, Nippon Kayaku, Takeda Pharmaceutical, MSD K.K., Amgen, Taiho Pharmaceutical, Bristol Myers Squibb, Janssen Pharmaceutical K.K., CMIC, Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Kobayashi Pharmaceutical, Pfizer Japan, AbbVie, A2 Healthcare, Eli Lilly Japan K.K., Medpace Japan K.K., EPS International, Covance Japan, EP-CRSU, GSK K.K., Sanofi K.K., Chugai Pharmaceutical, Nippon Boehringer Ingelheim, PRA Health Sciences, Astellas, Ascent Development Services, AstraZeneca K.K., Daiichi Sankyo, Novartis Pharma K.K., Merck Biopharma, Mochida Pharmaceutical, Japan Clinical Research Operations; Financial Interests, Institutional, Research Grant: Japanese Gastric Cancer Association, Clinical Research Support Center Kyushu, Japan Clinical Cancer Research Organization, Ono Pharmaceutical, Medical Research Support, Eisai, Shionogi & Co, Otsuka Pharmaceutical, Chugai Pharmaceutical, Nippon Boehringer Ingelheim, Bayer Yakuhin, Kyowa Kirin; Financial Interests, Institutional, Funding: SRL Medisearch, Eisai, Thoracic Oncology Research Group (TORG), West Japan Oncology Group (WJOG), Comprehensive Support Project for Oncological Research of Breast Cancer (CSPOR-BC), Mebix; Non-Financial Interests, Member: WJOG, Japanese Society of Medical Oncology.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing and editorial support was provided by Erinn Gideons, PhD, CMPP (Nucleus Global, an Inizio company), and was funded by the Daiichi Sankyo Company, Limited and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Editorial support was provided in accordance with Good Publication Practice guidelines (ismpp.org/gpp-2022).

Figures

Infographic:
Infographic:
A PDF version of this infographic is available as supplemental material.
Figure 1.
Figure 1.
HERTHENA-PanTumor01 study design.
See this image and copyright information in PMC

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