Hendrik-Tobias Arkenau (London, United Kingdom)
Sarah Cannon Research Institute UKAuthor Of 2 Presentations
161O - VIOLETTE: Randomised Phase 2 Study of Olaparib (ola) + Ceralasertib (cer) or Adavosertib (ada) vs Ola Alone in Patients (pts) With Metastatic Triple-Negative Breast Cancer (mTNBC) (ID 278)
- Andrew Tutt (London, United Kingdom)
- Zbigniew Nowecki (Warsaw, Poland)
- Renata Szoszkiewicz (Skorzewo, Poland)
- Seock-Ah Im (Seoul, Korea, Republic of)
- Hendrik-Tobias Arkenau (London, United Kingdom)
- Anne Armstrong (Manchester, United Kingdom)
- William Jacot (Montpellier, France)
- Jee Hyun Kim (Seongnam, Korea, Republic of)
- Marc Webster (Calgary, Canada)
- Judith Balmaña (Barcelona, Spain)
- Suzette Delaloge (Villejuif, France)
- Natasha Lukashchuk (Cambridge, United Kingdom)
- Ronny Odegbami (Cambridge, United Kingdom)
- Ed Casson (Cambridge, United Kingdom)
- Arsene B. Loembe (Oss, Netherlands)
- Moritz W. Drachsler (Cambridge, United Kingdom)
- Emma J. Dean (Cambridge, United Kingdom)
- Kevin Punie (Leuven, Belgium)
Abstract
Background
Combining DNA damage response (DDR) inhibitors to inhibit multiple DDR pathways may enhance tumour cell death. Preclinical models show synergistic antitumour effects of ola (PARP1 inhibitor) + cer (ATR inhibitor) or ada (WEE1 inhibitor). VIOLETTE (NCT03330847), a phase 2 open-label study, evaluated ola ± cer or ada as 2nd–3rd line in pts with mTNBC.
Methods
Randomisation was stratified within each arm by mutation status (BRCAm, non-BRCAm homologous recombination repair pathway mutations [HRRm], or no HRRm [non-HRRm]) based on a prospective central tumour test and prior platinum therapy. Pts received ola 300 mg BID, 28-d cycle; cer 160 mg d 1–7 + ola 300 mg BID (cer+ola), 28-d cycle; or ada 150 mg BID d 1–3, 8–10 + ola 200 mg BID (ada+ola), 21-d cycle. Primary study endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), safety, and tolerability. Ada+ola was discontinued early due to higher than expected grade ≥3 haematologic toxicity, which limited its interpretation. We focus on cer+ola vs ola. The sponsor stopped VIOLETTE after reviewing BRCAm stratum efficacy data.
Results
Of 273 pts (450 planned; median age: 53 y), 114 received ola, 112 cer+ola, and 47 ada+ola. Primary analyses showed no statistically significant difference in PFS for cer+ola vs ola (BRCAm: n=83; HR 1.02 [90% CI 0.63–1.66, P=0.94], HRRm: n=40; 0.54 [0.28–1.03, 0.13], non-HRRm: n=103; 0.76 [0.50–1.14, 0.30]). No statistically significant difference in ORR was seen for cer+ola vs ola in BRCAm (50% vs 44%) or HRRm (20% vs 15%). ORR was higher in non-HRRm for cer+ola (15%, n=8) vs ola (4%, n=2) (odds ratio 4.45; 90% CI 1.30–21.20, P=0.04). In all pts, nausea and anaemia were the most common adverse events (AEs). Grade ≥3 AEs: 36% ola, 47% cer+ola, 78% ada+ola. Details of exploratory and subgroup analyses will be presented.
Conclusions
Cer+ola did not improve PFS vs ola as 2nd–3rd line for mTNBC. Clinical significance of higher ORR with cer+ola in non-HRRm pts is unclear. Cer+ola had a manageable safety profile consistent with known profiles of each. Further analyses may identify pts likely to benefit from each treatment.
Clinical trial identification
NCT03330847.
Editorial acknowledgement
Medical writing assistance, funded by AstraZeneca, was provided by Anna Frangou, PhD, and Stephan Lindsey, PhD, of Peloton Advantage, LLC, an OPEN Health company, under the direction of the authors.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
A. Tutt: Financial Interests, Personal, Advisory Board, Personal fees /Advisory Board related to targeted therapies in DNA repair deficient: Pfizer; Financial Interests, Personal, Advisory Board, Personal fees from /Advisory Board related to targeted therapies in DNA repair deficient: Vertex; Financial Interests, Personal, Advisory Board, Personal fees/Advisory Board related to targeted therapies in DNA repair deficient: Artios; Financial Interests, Personal, Advisory Board, Personal fees/Advisory Board related to targeted therapies in DNA repair deficient: prIME Oncology; Financial Interests, Personal, Advisory Board, Personal Fees/Moon Shot Breast Cancer Scientific Advisory Board Honoraria: MD Anderson; Financial Interests, Personal, Advisory Board, Personal fees/Scientific Ad Board function and stock options: Inbiomotion; Financial Interests, Personal, Invited Speaker, Speaking role at mini symposium: SABCS 2020; Financial Interests, Personal, Advisory Board, Personal fees relating to advisory board: Gilead 21.05.21; Financial Interests, Institutional, Expert Testimony, CRUK expert panel monies going to my research account at the Institute of Cancer Research/Honoraria associated with Deputy Chair also going into research account: CRUK; Financial Interests, Institutional, Invited Speaker, Paid into research account at the Institute of Cancer Research: AZ Symposium ESMO 2021; Financial Interests, Personal, Advisory Board, Personal fees from Advisory Boards: MERCK Serano; Financial Interests, Institutional, Expert Testimony, Paid into research institute account: GE Healthcare 17.06.21; Financial Interests, Personal, Expert Testimony, Personal fees paid for expert testimony: EM Partners 16.06.21; Financial Interests, Institutional, Invited Speaker, Speaker at round table and monies went into research account: VJ Oncology 11.06.21; Financial Interests, Personal, Expert Testimony, Personal fees for an educational video: Medscape Education; Financial Interests, Personal, Advisory Board, Personal and institution fees for Ad Board: Gilead; Financial Interests, Personal, Full or part-time Employment, Head of Division for Breast Research, Director Breast Cancer Now Research Centre, Honorary Consultant Clinical Oncologist, Royal Marsden Hospital, joint leadership appointment with KCL that is processed through ICR payroll: Institute of Cancer Research; Financial Interests, Personal, Full or part-time Employment, Director of Breast Cancer Now Research Unit, King's College London, Honorary Consultant Clinical Oncologist, Breast Unit, Guy’s and St Thomas’ NHS Foundation Trust, joint leadership appointment with ICR that is processed through ICR payroll: King's College London; Financial Interests, Personal, Stocks/Shares: Inbiomotion; Financial Interests, Personal, Royalties, AstraZeneca with royalties paid to The Institute of Cancer Research (ICr) for the use of PARP inhibitors in DNA deficient cancers, licensee - AstraZeneca. ICR rewards to inventor's payments paid to Andrew Tutt's research accounts at The Institute of Cancer Research and to personal accounts: AstraZeneca; Financial Interests, Institutional, Research Grant, Received research support for TNT trial: Myriad genetics; Financial Interests, Personal and Institutional, Invited Speaker, Financial support to my academic and hospital institutions for costs associated with global academic study chair and local site costs for OlympiA trial/Travel expenses related to any trial related travel. Payments through Breast International Group for trial conduct in Olympic trial and through CRO's for commercial PARP inhibitor trial: AstraZeneca; Financial Interests, Institutional, Research Grant, Local site trial associated with clinical trial DNA: MERCK KGAA; Financial Interests, Institutional, Research Grant, Financial support for research at ICR: Medivation; Non-Financial Interests, Other, Member of Strategy Group: NCRI Strategy Group; Non-Financial Interests, Other, Member of the Committee: ESMO Guidelines Committee; Non-Financial Interests, Officer, Committee Member: ESMO 2023 Scientific Committee; Non-Financial Interests, Institutional, Product Samples, Responsible for care of patients receiving Olaparib on named patient programme in Breast Cancer @ Guy's London: Guy's Hospital; Other, Grant funded to study homologous recombination deficient breast and other cancers, BCN receive payments through AstraZeneca related to PARP inhibitor patents: Breast Cancer Now; Other, Grant funded to study homologous recombination deficient breast and other cancers, CRUK receive payments through AstraZeneca related to PARP inhibitor patents: CRUK. Z. Nowecki: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Sanofi Aventis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Other, Traveler Grant: Roche. R. Szoszkiewicz: Financial Interests, Personal, Principal Investigator: Centrum Medyczne Pratia Poznan. S. Im: Non-Financial Interests, Personal, Advisory Role: AstraZeneca; Non-Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Non-Financial Interests, Personal, Advisory Role: Eisai; Non-Financial Interests, Personal, Advisory Role: GSK; Non-Financial Interests, Personal, Advisory Role: Hanmi; Non-Financial Interests, Personal, Advisory Role: Idience; Non-Financial Interests, Personal, Advisory Role: Lilly; Non-Financial Interests, Personal, Advisory Role: MSD; Non-Financial Interests, Personal, Advisory Role: Pfizer; Non-Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Daewoong Pharm; Financial Interests, Institutional, Research Grant: Boryung Pharm; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Roche. H. Arkenau: Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: Guardant; Financial Interests, Personal, Advisory Board: iOnctura; Financial Interests, Personal, Advisory Board: Beigene; Financial Interests, Institutional, Invited Speaker: multiple small and large Pharma/Biotechs. A. Armstrong: Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Conference Fees: Gilead; Financial Interests, Personal, Other, Conference Fees: MSD; Financial Interests, Institutional, Other, Research Funding: AstraZeneca; Financial Interests, Personal, Other, Spousal Shares: AstraZeneca. W. Jacot: Financial Interests, Institutional, Other, Research Funding: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Other, Personal, Other, Congress Travel Support: AstraZeneca; Other, Personal, Other, Congress Travel Support: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly France; Other, Personal, Other, Congress Travel Support: Lilly France; Financial Interests, Personal, Advisory Board: Eisai; Other, Personal, Invited Speaker, Congress Travel Support: Eisai; Financial Interests, Personal, Advisory Board: BMS; Other, Personal, Other, Congress Travel Support: Chugai Pharma; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Other, Personal, Other, Congress Travel Support: Glaxo Smith Kline; Financial Interests, Personal, Advisory Board: Novartis; Other, Personal, Other, Congress Travel Support: Novartis; Financial Interests, Personal, Advisory Board: MSD; Other, Personal, Other, Congress Travel Support: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Other, Personal, Other, Congress Travel Support: Roche; Financial Interests, Personal, Advisory Board: Rain Pharmaceuticals; Other, Personal, Other, Congress Travel Support: Sanofi Aventis; Financial Interests, Personal, Advisory Board: Seagen. J.H. Kim: Financial Interests, Institutional, Other, Research Funding: Ono Pharma Korea Co., Ltd. M. Webster: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Knight; Financial Interests, Personal, Advisory Role: Gilead; Financial Interests, Personal, Advisory Role: Genomic Health. J. Balmana: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Pfizer. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pierre fabre; Financial Interests, Institutional, Advisory Board: Orion; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Rappta; Financial Interests, Institutional, Advisory Board: Cellectis; Financial Interests, Institutional, Advisory Board: Isis/servier; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker: Roche Genentech; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Orion; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. N. Lukashchuk: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. R. Odegbami, A.B. Loembe, M.W. Drachsler: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. E. Casson: Financial Interests, Personal, Full or part-time Employment, Independent contractor: AstraZeneca. E.J. Dean: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. K. Punie: Financial Interests, Personal, Other, Travel Support: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Advisory Board: Gilead Sciences; Financial Interests, Institutional, Invited Speaker: Medscape; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Institutional, Invited Speaker: MundiPharma; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Personal, Other, Travel Support: Pfizer; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Advisory Role: Pierre Fabre; Financial Interests, Personal, Other, Travel Support: Roche; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Institutional, Advisory Role: Roche; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Advisory Role: Teva; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Advisory Role: Vifor Pharma; Financial Interests, Personal, Other, Travel Support: PharmaMar.
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.