Sara A. Hurvitz (Los Angeles, United States of America)
UCLA, Jonsson Comprehensive Cancer CenterAuthor Of 4 Presentations
How can we improve the first-line treatment of HER2+ mBC? (ID 361)
162O - Primary analysis from DS8201-A-U105: A 2-part, open label, phase 1b trial assessing trastuzumab deruxtecan (T-DXd) with nivolumab (nivo) in patients (pts) with HER2-expressing advanced breast cancer (ID 304)
- Erika P. Hamilton (Nashville, United States of America)
- Charles L. Shapiro (New York, United States of America)
- Valentina Boni (Madrid, Spain)
- Miguel Martin Jimenez (Madrid, Spain)
- Gianluca Del Conte (Milan, Italy)
- Javier Cortes (Madrid and Barcelona, Spain)
- LAILA Agrawal (Louisville, United States of America)
- Hendrik-Tobias Arkenau (London, United Kingdom)
- Antoinette R. Tan (Charlotte, United States of America)
- Philip R. Debruyne (Cambridge, United Kingdom)
- Anna R. Minchom (London, United Kingdom)
- Annemie Rutten (Wilrijk, Belgium)
- Frances Valdes-Albini (Miami, United States of America)
- Evan Yu (Seattle, United States of America)
- Fumitaka Suto (Basking Ridge, United States of America)
- Fu-Chih Cheng (Basking Ridge, United States of America)
- Bincy Augustine (Basking Ridge, United States of America)
- Ben Cheng (Basking Ridge, United States of America)
- Daniel Barrios (Basking Ridge, United States of America)
- Sara A. Hurvitz (Los Angeles, United States of America)
Abstract
Background
In DESTINY-Breast01 (NCT03248492), T-DXd showed efficacy and safety in pts with HER2+ metastatic breast cancer (MBC) with prior T-DM1. Preclinical models showed that T-DXd combined with an anti–PD-1 antibody had greater efficacy vs either agent alone (Iwata Mol Cancer Ther 2018). This was a 2-part, open-label, multicenter, phase 1b study of T-DXd with nivo in pts with HER2-expressing MBC or advanced urothelial cancer (NCT03523572). Primary results from part 2 for MBC pts are reported.
Methods
Pts were immunotherapy naive with centrally confirmed HER2+ (IHC 3+ or IHC 2+/ISH+) MBC after T-DM1 or HER2 low (IHC 1+ or IHC 2+/ISH-) MBC after standard-of-care. Pts received the recommended dose for expansion T-DXd 5.4 mg/kg and nivo 360 mg IV Q3W. The primary endpoint was confirmed ORR (cORR) assessed by independent central review (ICR) per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), duration of response (DOR), and safety.
Results
At the primary analysis data cutoff (July 22, 2021), 48 pts (HER2+, n = 32; HER2 low, n = 16) received T-DXd and nivo. Median follow-up duration was 18.7 mo for HER2+ pts and 12.7 mo for HER2-low pts. The cORR by ICR was 65.6% (95% CI, 46.8-81.4) and 50% (95% CI, 24.7-75.3); median PFS was 11.6 mo (95% CI, 6.9-NE) and 7.0 mo (95% CI, 2.3-10.8); and median DOR was NE (95% CI, 7.9-NE) and 5.5 mo (95% CI, 2.8-8.0) for HER2+ and HER2 low pts, respectively. Overall, median treatment duration was 7.9 mo for T-DXd and 5.8 mo for nivo. In parts 1 and 2 (T-DXd 5.4 mg/kg, nivo 360 mg; n = 48), TEAEs grade ≥3 occurred in 50.0% of pts; nausea (56.3%) was the most common any-grade TEAE; and 7 (14.6%) HER2+ pts had adjudicated drug-related interstitial lung disease (6 grade 2; 1 grade 5).
Conclusions
Results of T-DXd plus nivo show antitumor activity consistent with previously reported data for T-DXd monotherapy in HER2+ BC, with no discernable benefit with the addition of nivo in this late-line setting. Data from the small HER2-low cohort are insufficient to determine the effects of PD-1/PD-L1 combination therapy. The combination safety profile was similar to that of each study drug as monotherapy.
Clinical trial identification
NCT03523572.
Editorial acknowledgement
Under the guidance of authors, assistance in medical writing and editorial support was provided by Jill Seabrook, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.
Legal entity responsible for the study
Daiichi Sankyo, Inc. and AstraZeneca.
Funding
Daiichi Sankyo, Inc. and AstraZeneca.
Disclosure
E.P. Hamilton: Financial Interests, Institutional, Advisory Board: Arcus, Arvinas, Black Diamond, Boehringer Ingelheim, CytomX, Daiichi Sankyo, Dantari, Deciphera Pharmaceuticals, Eisai, H3 Biomedicine, iTeos, Janssen, Lilly, Loxo, Merck, Mersana, Novartis, Pfizer, Puma Biotechnology, Relay Therapeutics, Roche/Genentech; Financial Interests, Institutional, Research Grant: AbbVie, Acerta Pharma, ADC Therapeutics, AKESOBIO Australia, Amgen, Aravive, 3 ArQule, Arvinas, AstraZeneca, AtlasMedx, Black Diamond, Boehringer Ingelheim, Clovis, Compugen, Curis, CytomX, Daiichi Sankyo, Dana Farber Cancer Inst., Deciphera, eFFECTOR The. C.L. Shapiro: Financial Interests, Personal, Other, Honoraria: UF Breast Symposium; Financial Interests, Personal, Advisory Board: 2nd MD, Anthenum, Gilead; Financial Interests, Personal, Other, Royalties: UptoDate. V. Boni: Financial Interests, Personal, Other, Honoraria: Director of Clinical Cancer Research, NEXT Madrid, Universitary Hospital QuirónSalud Pozuelo; Financial Interests, Institutional, Other, Honoraria: AbbVie; ACEO; Adaptaimmune; Amcure; Amgen; AstraZeneca; BMS Cytomx; GSK; Genentech/Roche; H3; Incyte; Janssen; Kura; Lilly; Loxo; Nektar; Macrogenics; Menarini; Merck; Merus; Nanobiotix; Novartis; Pfizer; PharmaMar; Principia; Puma; Sanofi; Taiho; Tesaro; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Ideaya Biosciences; Loxo Therapeutics, CytomX Therapeutics; Guidepoint; Oncoart; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly. M. Martin Jimenez: Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Daiichi Sankyo, Seagen, AstraZeneca, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: Roche, Novartis, Daiichi Sankyo, Seagen, AstraZeneca, Pfizer, Lilly; Financial Interests, Institutional, Research Grant: Roche, Puma, Novartis. G. Del Conte: Financial Interests, Personal, Advisory Board: Novartis, BMS; Financial Interests, Personal, Other, Travel Expenses: Janssen, Astellas, Pfizer. J. Cortés: Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymework; Financial Interests, Personal, Stocks/Shares: MedSIR; Financial Interests, Institutional, Research Grant: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman- La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca. L. Agrawal: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Immunomedics, Breast Cancer Index; Financial Interests, Personal, Speaker’s Bureau: Lilly. H. Arkenau: Financial Interests, Personal, Advisory Board: Roche, LabGenius, Cell Centric, Daiichi Sankyo, Bicycle Therapeutics; Guardant Health, BioNTech, Bayer, Beigene, Servier; Financial Interests, Personal, Other, Honoraria: Bicycle Therapeutics, BioNTech, Bayer, Beigene, Servier, Roche and Guardant Health; Financial Interests, Personal, Other, Travel Expenses: Amgen; Financial Interests, Personal, Full or part-time Employment: Sarah Cannon. A.R. Tan: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Research Grant: Daiichi Sankyo. P.R. Debruyne: Financial Interests, Personal, Other, Honoraria: BMS, Merck/Pfizer, MSD, Roche, Bayer; Financial Interests, Personal, Stocks/Shares: Alkermes; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen. A.R. Minchom: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceuticals, Novartis Oncology, Faron Pharmaceuticals, Bayer Pharmaceuticals; Financial Interests, Personal, Advisory Board: Janssen Pharmaceuticals, Merck Pharmaceuticals, Takeda Pharmaceuticals and Genmab Pharmaceuticals; Financial Interests, Personal, Other, Travel Expenses: Amgen Pharmaceuticals and LOXO Oncology. E. Yu: Financial Interests, Personal, Advisory Board: Advanced Accelerator Applications, Bayer, Janssen, Merck, Exelus, Clovis, AbbVie, Sanofi; Financial Interests, Invited Speaker: Daiichi Sankyo, Dendreon, Taiho, Merck, Seagen, Blue Earth, Bayer, Lantheus. F. Suto, F. Cheng, B. Augustine, B. Cheng, D. Barrios: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc. S.A. Hurvitz: Financial Interests, Institutional, Research Grant: Ambrx, Amgen, AstraZeneca, Arvinas, Bayer, Cytomx, Daiichi Sankyo, Dignitana, Genentech/Roche, Gilead, GSK, Immunomedics, Eli Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Orinove, Pieris, Puma, Radius, Sanofi, Seattle Genetics/Seagen, Zymeworks, Pho; Financial Interests, Personal, Principal Investigator: Novartis, Daiichi Sankyo, Seagen, GNE/Roche; Financial Interests, Personal, Advisory Board: Novartis, Lilly, Daiichi Sankyo/AZ, GNE/Roche, Sanofi; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Lilly; Non-Financial Interests, Personal, Other, Uncompensated consulting/ad boards: 4DPharma, Ambrx, Amgen, Artios, Arvinas, Daiichi Sankyo, Dantari, Genentech/Roche, Immunomedics, Macrogenics, Eli Lilly, Novartis, NK Max, Pieris, Pyxis, Seagen, Biotheranostics. All other authors have declared no conflicts of interest.
168P - Sacituzumab govitecan (SG) efficacy in patients with metastatic triple-negative breast cancer (mTNBC) by HER2 immunohistochemistry (IHC) status: Findings from the Phase 3 ASCENT study (ID 176)
- Sara A. Hurvitz (Los Angeles, United States of America)
- Aditya Bardia (Boston, United States of America)
- Kevin Punie (Leuven, Belgium)
- Kevin Kalinsky (Atlanta, United States of America)
- Javier Cortes (Madrid and Barcelona, Spain)
- Joyce O'Shaughnessy (Dallas, United States of America)
- Lisa A. Carey (Chapel Hill, United States of America)
- Hope S. Rugo (San Francisco, United States of America)
- Oh Kyu Yoon (Foster City, United States of America)
- Yang Pan (Foster City, United States of America)
- Rosemary J. Delaney (Foster City, United States of America)
- Scott Hofsess (Foster City, United States of America)
- Paul Hodgkins (Foster City, United States of America)
- See-Chun Phan (Foster City, United States of America)
- Veronique Dieras (Rennes, France)
Abstract
Background
HER2 IHC1+ or IHC2+ and in situ hybridization (ISH)-negative results are sometimes referred to as HER2-Low. SG is a novel antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to SN-38 via a proprietary, hydrolyzable linker. SG is approved in mTNBC for the second line (2L) onwards. In the ASCENT study, SG had significant progression-free survival (PFS) and overall survival (OS) benefit vs chemotherapy of physician’s choice (TPC). This ASCENT post hoc subgroup analysis evaluates SG efficacy in HER2 IHC0 and HER2-Low mTNBC.
Methods
Patients (pts) with mTNBC refractory/relapsing after ≥2 prior chemotherapies (≥1 in the metastatic setting) were randomized 1:1 to receive SG (10 mg/kg IV on d 1 and 8, every 21 d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until unacceptable toxicity/progression. Primary endpoint was PFS per RECIST 1.1 by central review. Pts with known HER2-positive disease were ineligible, but HER2 status was not assessed centrally in ASCENT. Local HER2 IHC results were analyzed retrospectively.
Results
In the intent-to-treat (ITT) population (SG vs TPC), 149 vs 144, 63 vs 60, and 55 vs 58 pts had HER2 IHC0, HER2-Low, and missing HER2 IHC results, respectively; 79% of the ITT population was HER2-evaluable. Baseline characteristics between HER2 IHC0 vs HER2-Low were comparable and similar to the ITT population. Median PFS and OS were significantly improved, and objective response rate was numerically higher with SG vs TPC in the HER2 IHC0 and HER2-Low groups (Table). HER2-Low had numerically better outcomes vs HER2 ICH0 in both the SG and TPC arms.
Conclusions
Clinical benefit with SG in HER2 IHC0 and HER2-Low mTNBC was consistent with that of the ASCENT ITT population, regardless of HER2 status. SG should be considered an effective treatment option for pts with mTNBC eligible for 2L or later therapy. ISH, in situ hybridization; HR, hazard ratio; IHC, immunohistochemistry; mPFS, median progression-free survival; mOS, median overall survival, ORR, objective response rate; SG, sacituzumab govitecan; TPC, treatment of physician’s choice ∗HER2-Low defined as IHC1+ or ICH2+ and ISH-neg
HER2 IHC0 HER2-Low∗ SG (n=149) TPC (n=144) SG (n=63) TPC (n=60) mPFS, mo 4.3 1.6 6.2 2.9 HR (95% CI) 0.38 (0.28-0.50) 0.44 (0.27-0.72) mOS, mo 11.3 5.9 14.0 8.7 HR (95% CI) 0.51 (0.39-0.66) 0.43 (0.28-0.67) ORR, n (%) 46 (31) 5 (3) 20 (32) 5 (8)
Clinical trial identification
NCT02574455.
Editorial acknowledgement
Editorial support was provided by Yao Bian, PhD, of Team 9 Science and funded by Gilead Sciences, Inc.
Legal entity responsible for the study
Gilead Sciences, Inc.
Funding
Gilead Sciences, Inc.
Disclosure
S.A. Hurvitz: Financial Interests, Personal, Invited Speaker: Clinical Care Options; Financial Interests, Personal, Invited Speaker: aptitude health; Financial Interests, Personal, Invited Speaker: axis medical; Financial Interests, Personal, Invited Speaker: cancer expert now; Financial Interests, Personal, Invited Speaker: ICHE; Financial Interests, Personal, Invited Speaker: MJH Associates; Financial Interests, Personal, Invited Speaker: PER; Financial Interests, Personal, Invited Speaker: Primo; Financial Interests, Personal, Invited Speaker: Projects in Knowledge; Financial Interests, Personal, Invited Speaker: Prova Education; Financial Interests, Personal, Invited Speaker: Research to Practice; Financial Interests, Personal, Invited Speaker: Ultimate Medical Academy; Financial Interests, Personal, Invited Speaker: Vaniam; Financial Interests, Personal, Invited Speaker: WebMD; Financial Interests, Personal, Invited Speaker: Rockpointe; Financial Interests, Personal, Invited Speaker: OBR; Financial Interests, Personal, Invited Speaker: Peer Education; Financial Interests, Personal, Invited Speaker: Spire Learning; Financial Interests, Personal, Invited Speaker: PrecisCA; Financial Interests, Personal, Stocks/Shares, stock options: NK Max; Financial Interests, Personal, Stocks/Shares, spouse owns: ROM Tech; Financial Interests, Personal, Ownership Interest, spouse: Ideal Implant; Financial Interests, Personal, Royalties, author medical book: McGraw; Financial Interests, Personal, Royalties: Elsevier; Financial Interests, Personal, Royalties: Springer; Financial Interests, Personal, Royalties: Sage; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Royalties: Wiley; Financial Interests, Institutional, Invited Speaker: Ambrx; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Arvinas; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Genentech/Roche; Financial Interests, Institutional, Invited Speaker: Gilead; Financial Interests, Institutional, Invited Speaker: GSK; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: OBI Pharma; Financial Interests, Institutional, Invited Speaker: Pieris; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Institutional, Invited Speaker: Radius; Financial Interests, Institutional, Invited Speaker: sanofi; Financial Interests, Institutional, Invited Speaker: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Dignitana; Financial Interests, Institutional, Invited Speaker: Zymeworks; Financial Interests, Institutional, Invited Speaker: Phoenix Molecular Designs, Ltd.; Financial Interests, Institutional, Research Grant: Samumed; Financial Interests, Institutional, Research Grant: Ambrx; Non-Financial Interests, Advisory Role: Daiichi Sankyo; Non-Financial Interests, Principal Investigator: Daiichi Sankyo; Non-Financial Interests, Advisory Role: Novartis; Non-Financial Interests, Principal Investigator: Genentech; Non-Financial Interests, Principal Investigator: Seattle Genetics; Non-Financial Interests, Advisory Role: Ambrx; Non-Financial Interests, Advisory Role: 4DPharma; Non-Financial Interests, Advisory Role: Dantari; Non-Financial Interests, Advisory Role: Macrogenics; Non-Financial Interests, Advisory Role: Lilly; Non-Financial Interests, Advisory Role: Artios; Non-Financial Interests, Advisory Role: Roche; Non-Financial Interests, Advisory Role: Pyxis; Non-Financial Interests, Advisory Role: Amgen; Non-Financial Interests, Advisory Role: Pieris; Non-Financial Interests, Advisory Role: Arvinas; Non-Financial Interests, Advisory Role: Immunomedics/Gilead; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: AACR; Non-Financial Interests, Other, speaker: National Breast Cancer Coalition; Non-Financial Interests, Member, site representative for breast cancer guidelines: National Comprehensive Cancer Network. A. Bardia: Financial Interests, Institutional, Financial Interests, grants: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health/Menarini, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly; Financial Interests, Personal, Financial Interests, consulting fees: Pfizer, Novartis, Genentech, Merck, Radius Health/Menarini, Immunomedics/Gilead, Sanofi, Daiichi Pharma/AstraZeneca, Phillips, Eli Lilly, Foundation Medicine. K. Punie: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board: Vifor Pharma; Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Mundi Pharma; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Advisory Board: McCann Health; Financial Interests, Institutional, Advisory Board: Roularta; Financial Interests, Institutional, Advisory Board: Teva; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: Gilead Sciences; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Other, Consultancy: Roche; Financial Interests, Institutional, Funding: Sanofi; Non-Financial Interests, Principal Investigator: EORTC 1745-ETF-BCG trial; Non-Financial Interests, Other, Committee member: ESMO Young Oncologists Committee; Non-Financial Interests, Invited Speaker: BSMO; Non-Financial Interests, Other, Committee Member: ESMO Resilience Task Force; Non-Financial Interests, Advisory Role: Commission personalized medecine Federal Government Belgium. K. Kalinsky: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Cyclacel; Financial Interests, Personal, Advisory Board: Oncosec; Financial Interests, Personal, Advisory Board: 4D Pharma; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Stocks/Shares, Employment + Stock = spouse: Grail; Financial Interests, Institutional, Invited Speaker: Incyte; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Genentech; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Calithera; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Acetylon; Financial Interests, Institutional, Invited Speaker: Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Zentalis; Financial Interests, Institutional, Invited Speaker: CytomX Therapeutics; Other, Support for attending meetings and/or travel: Eli Lilly; Other, Support for attending meetings and/or travel: AstraZeneca; Other, Support for attending meetings and/or travel: Pfizer; Other, Steering Committee: Immunomedics; Other, Steering Committee: AstraZeneca; Other, Steering Committee: Ambryx; Other, Steering Committee: Genentech. J. Cortés: Financial Interests, Personal, Financial Interests, stock: Leuko, MedSIR, Nektar; Financial Interests, Personal, Financial Interests, honoraria: Novartis, Eisai, Celgene, Pfizer, Roche, Samsung, Lilly, Merck Sharp & Dohme, Daachi Sankyo; Financial Interests, Personal, Financial Interests, consulting or advisory role: Celgene, Cellestia Biotech, AstraZeneca, Roche, Seattle Genetics, Daachi Sankyo, ERYTECH Pharma, Polyphor, Athenex, Lilly, Servier, Merck Sharp & Dohme, GlaxoSmithKline, Leuko, Clovis Oncology, Bioasis, Boehringer, Ingelheim, Ellipses Pharma, HiberCell; Financial Interests, Institutional, Financial Interests, research funding: Ariad, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer, Eisai Farmaceutica, Guardaanth Health, Merck Sharp & Dohme, Pfizer, Puma Co, Queen Mary University of London, Roche, Piqur; Financial Interests, Personal, Financial Interests, travel, accomodations, expenses: Roche, Pfizer, Eisai, Novartis, Daiichi Sankyo. J. O'Shaughnessy: Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Agendia; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Aptitude Health; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: G1 Therapeutics; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Ipsen Biopharmaceuticals; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Myriad; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Ondonate; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: prIME Oncology; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Syndax. H.S. Rugo: Financial Interests, Personal, Invited Speaker: Puma; Financial Interests, Personal, Advisory Board: samsung; Financial Interests, Personal, Invited Speaker: mylan; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: OBI Pharma; Financial Interests, Institutional, Invited Speaker: Immunomedics; Financial Interests, Institutional, Invited Speaker: Macrogenics; Financial Interests, Institutional, Invited Speaker: Daiichi; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Invited Speaker: Odonate; Financial Interests, Institutional, Invited Speaker: sermonix; Financial Interests, Institutional, Invited Speaker: seattle genetics; Financial Interests, Institutional, Invited Speaker: polyphor; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. O.K. Yoon: Financial Interests, Personal, Financial Interests, employee, stock options: Gilead. Y. Pan: Financial Interests, Personal, Financial Interests, employee: Gilead. R.J. Delaney: Financial Interests, Personal, Financial Interests, employee, stock or stock options: Gilead. S. Hofsess: Financial Interests, Personal, Financial Interests, employee, meeting attendance, stock options: Gilead; Non-Financial Interests, Personal, Non-Financial Interests, unpaid: Chair of the William Paterson University Professional Science Master’s External Advisory Board. P. Hodgkins: Financial Interests, Personal, Financial Interests, employee, stock options: Gilead Sciences. S. Phan: Financial Interests, Personal, Financial Interests, employee, grants or contracts, meeting attendance, stock or stock options, receipt of materials: Gilead. V. Dieras: Financial Interests, Personal, Financial Interests, consulting fees: Roche Genentech, Novartis, Pfizer, Lilly, AbbVie, Eisai, AstraZeneca, Daiichi Sankyo, Seagen, Gilead, MSD, Pierre Fabre Oncologie; Financial Interests, Personal, Financial Interests, honoraria: Novartis, Pfizer, Lilly, AstraZeneca, Seagen, Daiichi Sankyo, Gilead, MSD; Financial Interests, Personal, Financial Interests, meeting attendance and/or travel: Roche, Novartis, Pfizer, Seagen, Lilly, AstraZeneca, Daiichi Sankyo, Gilead; Financial Interests, Personal, Financial Interests, data safety monitoring board or advisory board: Roche Genentech, Novartis, Pfizer, Lilly, AbbVie, Eisai, AstraZeneca, Daiichi Sankyo, Seagen, Gilead, MSD, Pierre Fabre Oncologie. All other authors have declared no conflicts of interest.
250TiP - HER2-positive and HER2-low Breast Cancer Patients in the ACE-Pan tumor-01 study: Phase 1 Study evaluating ARX788 as Monotherapy in Advanced Solid Tumors with HER2-expression or mutation (ID 217)
- Janice Lu (Los Angeles, United States of America)
- G. Thomas Budd (Cleveland, United States of America)
- Sophia Frentzas (Bentleigh East, Australia)
- Haeseong Park (St. Louis, United States of America)
- Cath Shannon (Brisbane, Australia)
- Hope S. Rugo (San Francisco, United States of America)
- Joyce O'Shaughnessy (Dallas, United States of America)
- Angela Demichele (Philadelphia, United States of America)
- Sara M. Tolaney (Boston, United States of America)
- Richard W. Eek (Wodonga, Australia)
- Amelia McCartney (Clayton, Australia)
- Katharine Cuff (Brisbane, Australia)
- Laura Esserman (San Francisco, United States of America)
- Alex Alika (La Jolla, United States of America)
- Dong Xu (La Jolla, United States of America)
- Matt Li (La Jolla, United States of America)
- Thuy Le (La Jolla, United States of America)
- Darryl Z. L'Heureux (La Jolla, United States of America)
- Joy Yan (La Jolla, United States of America)
- Sara A. Hurvitz (Los Angeles, United States of America)
Abstract
Background
HER2-targeted therapies have changed the treatment landscape for pts with HER2-positive (+) breast cancer (BC), but the clinical benefit of these first-generation HER2 targeted agents is just emerging for patients with HER2-low disease. HER2-low, defined as IHC 1-2+ without HER2 gene amplification, comprises between 40-65% of HER2-negative breast cancer. While HER2-positive BC comprises approximately 20% of newly diagnosed cases, a greater proportion of patients (∼50%) have BC categorized as HER2-low (IHC 1-2+ but ISH negative) and have a high unmet medical need. Even with the success of anti-HER2 treatments for HER2+ patients, many patients become resistant or are refractory to treatment. A new generation of anti-HER2 targeted agents has recently demonstrated both clinical activity and safety in HER2-low BC, including ARX788, an anti-HER2 antibody drug conjugate (ADC). ARX788 is a site-specific conjugated ADC that consists of a HER2 targeting monoclonal antibody (mAb) with payload AS269, a highly potent tubulin inhibitor. Site-specificity, high homogeneity, and stable covalent conjugation of ARX788 leads to its slow release and prolonged peak of serum pAF-AS269, which may contribute to the lower systemic toxicity and increased targeted delivery of payload to tumor cells at a lower effective dose compared to other HER2 ADCs.
Trial design
ACE-Pan tumor-01 (NCT03255070) is a global phase 1 study to assess efficacy and safety of ARX788 in patients with metastatic HER2+ BC, HER2-low BC, HER2+ GC (gastric cancer), or other advanced solid tumors with HER2 overexpression or activating mutations (including BC). Eligibily includes non-operable Stage III-IV disease, measurable lesions. HER2+ cohort must be resistant/refractory to T-DM1, and/or T-DXd, and/or tucatinib containing regimens, while HER2 low cohort must have no standard curative/palliative measures. Endpoints: ORR, DOR, TTR, BOR, DCR, PFS, and OS using RECIST1.1. Safety assessed by PE, AEs, VS, ECG, and lab tests PK, immunogenicity, biomarkers to be analyzed. Descriptive statistics will be used. As of Feb/2022, 28 patients with ongoing enrollment.
Clinical trial identification
NCT03255070.
Legal entity responsible for the study
Ambrx, Inc.
Funding
Ambrx, Inc.
Disclosure
D. Xu, M. Li, T. Le: Financial Interests, Personal, Full or part-time Employment: Ambrx. J. Yan: Financial Interests, Personal, Member of the Board of Directors: Ambrx. All other authors have declared no conflicts of interest.