Abstract 690TiP
Background
Human epidermal growth factor receptor 3 (HER3) is a member of the HER/EGFR family of receptor tyrosine kinases and is expressed in numerous solid tumors; higher HER3 expression in some tumor types is associated with poor clinical outcomes. HERTHENA-PanTumor01 (NCT06172478) is a global, multicohort, phase 2 trial evaluating the efficacy and safety of HER3-DXd—a first-in-class, HER3-directed antibody-drug conjugate (ADC)—in previously treated patients (pts) with locally advanced or metastatic tumors.
Trial design
Each cohort will enroll 40 pts to explore HER3-DXd 5.6 mg/kg IV Q3W in tumor types beyond NSCLC and breast cancer. Three cohorts (melanoma, head and neck cancers, and gastric cancer) were previously introduced; 7 new cohorts—bladder, cervical, endometrial, esophageal, ovarian, pancreatic, and prostate cancer—are presented here (Table). Pts who received prior treatment with an anti-HER3 antibody and/or ADC that consists of an exatecan derivative are excluded. A fresh or archival biopsy performed after progression on the most recent cancer therapy is to be obtained, which can be waived in extenuating circumstances. Tumor assessments occur every 6 wk for the first 48 wk, then every 12 wk. Pts with clinically inactive or asymptomatic brain metastases are allowed if they have a stable neurologic status for ≥4 weeks prior to C1D1 and will undergo MRI scans during tumor assessments. For pts with prostate cancer, a bone scan will occur within 28 d before treatment and then during tumor assessments; prostate-specific antigen (PSA) will be assessed at every cycle. The primary endpoint is ORR by investigator per RECIST version 1.1 except for prostate cancer, which has a primary endpoint of PSA50 response rate. Intracranial response will be assessed by BICR per CNS-RECIST in the melanoma cohort. Other endpoints include safety, additional efficacy endpoints (DOR, CBR, DCR, TTR, PFS, OS), PK, and biomarkers. Study sites are in Asia, Australia, Europe, and the US. Table: 690TiP
| Tumor | Required previous treatments |
| Bladder cancer | 1-3 lines of therapy (LOT); anti–PD-(L)1 antibody and ≥1 line of chemotherapy or enfortumab vedotin |
| Cervical cancer | ≥1 LOT |
| Endometrial cancer | 1-3 LOTs; platinum-based chemotherapy (PBC) ± anti–PD-(L)1 antibody |
| Esophageal cancer | 2 LOTs; PBC ± anti–PD-1 antibody |
| Gastric cancer | ≥2 LOTs; PBC ± anti–PD-(L)1 antibody |
| Head and neck cancers | ≥1 to Clinical trial identificationNCT06172478. Editorial acknowledgementMedical writing support was provided by Erinn Gideons, PhD, CMPP (Nucleus Global, an Inizio company). Legal entity responsible for the studyDaiichi Sankyo Company, Limited and Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc. FundingDaiichi Sankyo Company, Limited and Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc. DisclosureT.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, 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 Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Other, honoraria: Gilead; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai; Financial Interests, Institutional, Other, Honoraria: Gilead. A.K. Bhatia: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Coherus, Regeneron, BMS; 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, Principal Investigator: Janssen. B. Burtness: Financial Interests, Personal, Advisory Board: GSK, Merck, Merck KgA, 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; Non-Financial Interests, Institutional, Proprietary Information: Merck; Non-Financial Interests, Institutional, Product Samples: Vitrac Pharmaceuticals. 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 Co., Ltd., MSD. C. Fountzilas: Financial Interests, Institutional, Research Grant: Pfizer Inc, Taiho Oncology, Merck Sharp & Dohme Corp.; Financial Interests, Institutional, Local PI: Seattle Genetics, Inc., TransThera Biosciences, AstraZeneca, Aravive, Inc., Merck Sharp & Dohme Corp., Kadmon, Astellas Pharma, Dragonfly Therapeutics, Rafael Pharmaceuticals, Ipsen, CG Pharmaceuticals, Biomea Fusion, Bellicum, Amgen Inc., Legend Biotech; Non-Financial Interests, Institutional, Other, Principal Investigator on clinical trial evaluating biomarker for treatment selection in pancreatic cancer: Valar Labs. M. Mckean: Financial Interests, Institutional, Other, Consulting: Pfizer, Castle Biosciences, IQVIA, Merck, Moderna; Financial Interests, Institutional, Research Grant: Acentage Pharma Group, Bicycle Therapeutics, Dragonfly Therapeutics, Epizyme, Exelixis, Genentech, GSK, Ideaya Biosciences, Ikena Oncology, Infinity Pharmaceuticals, Jacobio Pharmaceuticals, Moderna, NBE Therapeutics, Novartis, Oncorus, Plexxicon, Prelude Therapeutics, Regeneron, Sapience Therapeutics, Seattle Genetics, Tizona Therpeutics, Tmunity Therapeutics, TopAlliance Biosciences, Aadi Biosciences, Alpine Immune Sciences, Arcs Biosciences, Arvinas, ASCO, Astellas, Bayer, BioMed Valley Discoveries, BioNTech, C4 Therapeutics, EMD Serono, Erasca, Foghorn Therapeutics, G1 Therapeutics, Gilead Sciences, ImmVira Pharma, Kechow Pharma, Kezar Life Sciences, Kinnate BioPharma, MedImmune, Mereo BioPharma, Metabomed, Nektar, OncoC4, PACT Pharma, Pfizer, Poseida, Pyramid Biosciences, Scholar Rock, Synthrox, Takeda Pharmaceuticals, Teneobio, Tempest Therapeutics, Xilio, Aulos Bioscienc, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, InconVir, Jazz Pharmaceutical, 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, FogPharma, 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 Inc., Daiichi Sankyo Co. Ltd., eFfector Therapeutics, Taiho Pharmaceutical Co.; Financial Interests, Institutional, Other, Local PI / Research Grant / Coordinating PI: AstraZeneca; Financial Interests, Institutional, Local PI: Calithera Biosciences, Curis Inc., Debiopharm International, Guardant Health Inc., Klus Pharma, Novartis, Jazz Pharmaceuticals, Zymeworks; Financial Interests, Institutional, Other, Local PI / Steering Committee Member: Genentech Inc.; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical Co., Puma Biotechnology Inc., 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: Onxerna; 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, Principal Investigator: AstraZeneca, MSD, pfizer, meru, calliditas, isa. 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, DMC: Alkermes. D.W. Sternberg, K.H. Sullivan, S. Yueh, G. Clinthorne, R. Kudchadkar: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc.; Financial Interests, Personal, Stocks or ownership: Daiichi Sankyo, Inc. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo K.K, Eli Lilly Japan K.K, Merck Biopharma Co. Ltd, MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb Co. Ltd, Eli Lilly Japan K.K, Pfizer, AstraZeneca K.K, Daiichi Sankyo Co.Ltd; Financial Interests, Personal, Royalties, Currently no provided: Sysmex; Financial Interests, Personal, Steering Committee Member: Janssen Pharmaceutical K.K., GSK plc., Daiichi Sankyo, Inc.; Financial Interests, Institutional, Local PI: IQVIA Services Japan K.K, Syneos Health Clinical K.K., EPS Corporation, Nippon Kayaku Co.,Ltd., Takeda Pharmaceutical Co.,Ltd., MSD K.K., Amgen Inc., Taiho Pharmaceutical Co.,Ltd., Bristol Myers Squibb Company, Janssen Pharmaceutical K.K., CMIC CO., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Kobayashi Pharmaceutical Co., Ltd., Pfizer Japan Inc., AbbVie Inc., A2 Healthcare Corp., Eli Lilly Japan K.K., Medpace Japan KK, EPS International Co.,Ltd,., Covance Japan Inc., EP-CRSU CO., Ltd., GSK K.K., Sanofi K.K., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., PRA Health Sciences Inc., Astellas Pharma Inc., Ascent Development Services, AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Novartis Pharma K.K., Merck Biopharma Co., Ltd, Mochida Pharmaceutical Co., Ltd., Japan Clinical Research Operations; Financial Interests, Institutional, Research Grant: Japanese Gastric Cancer Association, Clinical Research Support Center Kyushu, Japan Clinical Caner Research Organization, Ono Pharmaceutical Co.,Ltd., Medical Research Support, Eisai Co., Ltd, Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Bayer Yakuhin, Ltd, Kyowa Kirin Co.,Ltd.; Financial Interests, Institutional, Funding: SRL Medisearch Inc., Eisai Inc., Thoracic Oncology Research Group (TORG), West Japan Oncology Group (WJOG), Comprehensive Support Project for Oncological Research of Breast Cancer (CSPOR-BC), Mebix, Inc.; Non-Financial Interests, Member: West Japan Oncology Group, Japanese Society of Medical Oncology. All other authors have declared no conflicts of interest. 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