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ePoster Display

259P - Weekly ladiratuzumab vedotin monotherapy for metastatic triple-negative breast cancer

Date

16 Sep 2021

Session

ePoster Display

Presenters

Michaela Tsai

Citation

Annals of Oncology (2021) 32 (suppl_5): S457-S515. 10.1016/annonc/annonc689

Authors

M. Tsai1, H.S. Han2, A.J. Montero3, K.H. Tkaczuk4, H. Assad5, L. Pusztai6, S.A. Hurvitz7, S.T. Wilks8, J.M. Specht9, R. Nanda10, M. Mita11, J. O'Shaughnessy12, I.E. Krop13, D. Medgyesy14, J. Abraham3, S. Modi15, H. Li16, S. Wu17, P.M. Garfin18, H.A. Burris III19

Author affiliations

  • 1 Oncology, Virginia Piper Cancer Institute, Allina Health, 55407 - Minneapolis/US
  • 2 Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa/US
  • 3 Oncology, Case Western Reserve University, University Hospitals/Seidman Cancer Center, Cleveland/US
  • 4 Oncology, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical System, Baltimore/US
  • 5 Oncology, Karmanos Cancer Center, Wayne State University, Detroit/US
  • 6 Oncology, Yale Cancer Center, New Haven/US
  • 7 Oncology And Hematology, University of California, Los Angeles; Jonsson Comprehensive Cancer Center, Los Angeles/US
  • 8 Oncology, Texas Oncology, San Antonio/US
  • 9 Oncology, Seattle Cancer Care Alliance, University of Washington, Seattle/US
  • 10 Oncology And Hematology, University of Chicago Medicine, Chicago/US
  • 11 Oncology, Cedars-Sinai Medical Center, Los Angeles/US
  • 12 Oncology And Hematology, Baylor University Medical Center, Texas Oncology, US Oncology, 75246 - Dallas/US
  • 13 Oncology, Dana Farber Cancer Institute, Boston/US
  • 14 Oncology And Hematology, UCHealth Poudre Valley Hospital, University of Colorado, Fort Collins/US
  • 15 Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 16 Clinical Pharmacology, Seagen Inc., Seattle/US
  • 17 Biostatistics, Seagen Inc., Seattle/US
  • 18 Late Stage Development, Seagen Inc., Seattle/US
  • 19 Oncology, Sarah Cannon Research Institute, Nashville/US
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Abstract 259P

Background

LIV-1 is highly expressed in breast cancer. Ladiratuzumab vedotin (LV) is an investigational anti-LIV-1 antibody-drug conjugate with a protease-cleavable linker conjugated to monomethyl auristatin E (MMAE). LV 2.5 mg/kg given every 3 weeks (q3w) was generally well tolerated and has demonstrated encouraging efficacy in patients with pre-treated metastatic triple-negative breast cancer (mTNBC). Here, we evaluated the efficacy and tolerability of weekly LV dosing (q1w).

Methods

SGNLVA-001 (NCT01969643) is an ongoing, multi-part, open label study investigating the safety and efficacy of LV in patients with metastatic breast cancer (mBC). Part E evaluated LV q1w in escalation and expansion starting at LV 1.0 mg/kg q1w. Patients with first (1L) or second line (2L) endocrine therapy refractory hormone receptor-positive (HR+)/HER2-negative (HER2-) mBC or 2L mTNBC were enrolled. Tumor assessments occurred every 6 weeks per RECIST v1.1.

Results

As of March 19, 2021, 81 patients were treated in Part E (median age 55 years, female 100%, ECOG-0 62%, subtype: mTNBC 49%, HR+/HER2- 51%). No dose limiting toxicities occurred with either LV 1.0, 1.25, or 1.5 mg/kg q1w. At LV 1.5 mg/kg, neutropenia was reported in 6 of 9 patients (66%; 1 Grade 1, 1 Grade 2, 1 Grade 3, and 3 Grade 4). Subsequent enrollment continued only in the LV 1.25 mg/kg cohort. The most common treatment emergent adverse events (TEAEs) observed with LV 1.25 mg/kg q1w (n=52) were nausea (60%), fatigue (58%), peripheral sensory neuropathy (54%), decreased appetite (44%), and constipation (39%). The most common ≥ Grade 3 TEAEs were neutropenia (21%), fatigue (14%), and hyperglycemia, hypokalemia, and hypophosphatemia (12% each). The most common serious adverse events were pneumonia (6%) and abdominal pain (4%). In the 29 patients with 2L mTNBC who received LV 1.25 mg/kg, the confirmed objective response rate was 28% (95% CI: 13, 47). Pharmacokinetic analyses indicate q1w dosing reduced peak-trough fluctuations, lowered Cmax while maintaining a higher Ctrough compared to q3w dosing.

Conclusions

LV 1.25 mg/kg q1w is associated with a manageable safety profile and favorable preliminary efficacy data in patients with 2L mTNBC. Further studies of LV q1w in patients with breast cancer and other tumors are underway.

Clinical trial identification

NCT01969643.

Editorial acknowledgement

Medical writing assistance was funded by Seagen Inc., and provided by Sandra Hackelberg of MMS Holdings, Inc.

Legal entity responsible for the study

Seagen Inc.

Funding

Seagen Inc.

Disclosure

H.S. Han: Financial Interests, Institutional, Sponsor/Funding: Arvinas; Financial Interests, Institutional, Sponsor/Funding: AbbVie; Financial Interests, Institutional, Sponsor/Funding: Bristol Myers Squibb; Financial Interests, Institutional, Sponsor/Funding: Daiichi Sankyo; Financial Interests, Institutional, Sponsor/Funding: G1 Therapeutics; Financial Interests, Institutional, Sponsor/Funding: GlaxoSmithKline; Financial Interests, Institutional, Sponsor/Funding: Horizon; Financial Interests, Institutional, Sponsor/Funding: Karyopharm; Financial Interests, Institutional, Sponsor/Funding: Marker Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Novartis; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: Prescient; Financial Interests, Institutional, Sponsor/Funding: Seagen; Financial Interests, Institutional, Sponsor/Funding: Zymeworks; Financial Interests, Personal, Speaker’s Bureau: Lilly. A.J. Montero: Financial Interests, Personal, Advisory Role: Welwaze; Financial Interests, Personal, Advisory Board: Oncosec; Financial Interests, Personal, Advisory Role: New Century Health; Financial Interests, Institutional, Sponsor/Funding: Roche; Financial Interests, Institutional, Sponsor/Funding: Genmab; Financial Interests, Institutional, Sponsor/Funding: Seagen; Non-Financial Interests, Personal, Advisory Role: FDA-ODAC. L. Pusztai: Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: Pieris; Financial Interests, Personal, Advisory Role: Syndex; Financial Interests, Personal, Advisory Role: Almac; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: Merck; Financial Interests, Institutional, Sponsor/Funding: Seagen; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: Bristol Myers Squibb; Non-Financial Interests, Personal, Principal Investigator: Merck; Non-Financial Interests, Personal, Other, Chair: SWOG Clinical Trial Network; Non-Financial Interests, Personal, Member: ASCO Breast Cancer Guideline Advisory Group; Non-Financial Interests, Personal, Member: ASCO Breast Cancer Biomarkers Guideline Panel; Non-Financial Interests, Personal, Member: ASCO Conquer Cancer Foundation Award Committee; Non-Financial Interests, Personal, Advisory Role: SABCS; Non-Financial Interests, Personal, Advisory Role: AACR; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Member: AACR; Non-Financial Interests, Personal, Member: American College of Physicians; Non-Financial Interests, Personal, Advisory Role: Susan Komen Foundation; Non-Financial Interests, Personal, Advisory Board: Breast Cancer Research Foundation; Non-Financial Interests, Personal, Member of the Board of Directors: HOPE Foundation. S.A. Hurvitz: Financial Interests, Personal, Stocks/Shares: NK Max; Financial Interests, Institutional, Research Grant: Ambrx; Financial Interests, Institutional, Sponsor/Funding: Ambrx; Financial Interests, Institutional, Sponsor/Funding: Arvinas; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: Bayer; Financial Interests, Institutional, Sponsor/Funding: Daiichi Sankyo; Financial Interests, Institutional, Sponsor/Funding: Dignitana; Financial Interests, Institutional, Sponsor/Funding: Genentech/Roche; Financial Interests, Institutional, Sponsor/Funding: Gilead; Financial Interests, Institutional, Sponsor/Funding: GSK; Financial Interests, Institutional, Sponsor/Funding: Immunomedics; Financial Interests, Institutional, Sponsor/Funding: Lilly; Financial Interests, Institutional, Sponsor/Funding: Macrogenics; Financial Interests, Institutional, Sponsor/Funding: Novartis; Financial Interests, Institutional, Sponsor/Funding: OBI Pharma; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: Phoenix Molecular Designs; Financial Interests, Institutional, Sponsor/Funding: Pieris; Financial Interests, Institutional, Sponsor/Funding: PUMA; Financial Interests, Institutional, Sponsor/Funding: Radius; Financial Interests, Institutional, Research Grant: Samumed; Financial Interests, Institutional, Sponsor/Funding: Sanofi; Financial Interests, Institutional, Sponsor/Funding: Seagen; Financial Interests, Institutional, Sponsor/Funding: Zymeworks. J.M. Specht: Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Advisory Board: Nektar; Financial Interests, Institutional, Sponsor/Funding: Merck; Financial Interests, Institutional, Sponsor/Funding: Genentech; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: Nektar; Financial Interests, Institutional, Sponsor/Funding: Xencor; Financial Interests, Institutional, Sponsor/Funding: Cascadian Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Myriad Pharmaceuticals; Financial Interests, Institutional, Sponsor/Funding: Novartis; Financial Interests, Institutional, Sponsor/Funding: Minerva Biotechnologies; Financial Interests, Institutional, Sponsor/Funding: Seagen; Non-Financial Interests, Personal, Principal Investigator: Translational Breast Cancer Research Consortium. R. Nanda: Financial Interests, Personal, Advisory Board: Aduro; Financial Interests, Personal, Advisory Board: Cardinal Health; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: Fujifilm; Financial Interests, Personal, Advisory Board: G1 Therapeutics; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Immunomedics/Gilead; Financial Interests, Personal, Advisory Board: Ionis; Financial Interests, Personal, Advisory Board: iTeos; Financial Interests, Personal, Advisory Board: MacroGenics; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Oncosec; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Role: G1 Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Arvinas; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: Celgene; Financial Interests, Institutional, Sponsor/Funding: Corcept Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Genentech/Roche; Financial Interests, Institutional, Sponsor/Funding: Immunomedics; Financial Interests, Institutional, Sponsor/Funding: Merck; Financial Interests, Institutional, Sponsor/Funding: OBI Pharma; Financial Interests, Institutional, Sponsor/Funding: Odonate Therapeutics; Financial Interests, Institutional, Sponsor/Funding: OncoSec; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: Seagen; Financial Interests, Institutional, Sponsor/Funding: Taiho. J. O'Shaughnessy: Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Agendia; Financial Interests, Personal, Advisory Role: Amgen Biotechnology; Financial Interests, Personal, Advisory Role: Aptitude Health; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Celgene Corporation; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: G1 Therapeutics; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Gilead Sciences; Financial Interests, Personal, Advisory Role: GRAIL; Financial Interests, Personal, Advisory Role: Halozyme Therapeutics; Financial Interests, Personal, Advisory Role: Heron Therapeutics; Financial Interests, Personal, Advisory Role: Immunomedics; Financial Interests, Personal, Advisory Role: Ipsen Biopharmaceuticals; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Myriad; Financial Interests, Personal, Advisory Role: Nektar Therapeutics; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Pharmacyclics; Financial Interests, Personal, Advisory Role: Pierre Fabre Pharmaceuticals; Financial Interests, Personal, Advisory Role: Puma Biotechnology; Financial Interests, Personal, Advisory Role: Prime Oncology; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Samsung Bioepis; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: Syndax Pharmaceuticals; Financial Interests, Personal, Advisory Role: Taiho Oncology; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Synthon. I.E. Krop: Financial Interests, Institutional, Sponsor/Funding: Bristol Myers Squibb; Financial Interests, Institutional, Sponsor/Funding: Daiichi/Sankyo; Financial Interests, Institutional, Sponsor/Funding: Macrogenics; Financial Interests, Institutional, Sponsor/Funding: Context Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Taiho Oncology; Financial Interests, Institutional, Sponsor/Funding: Genentech/Roche; Financial Interests, Institutional, Sponsor/Funding: Seagen; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: NOVARTIS; Financial Interests, Institutional, Sponsor/Funding: Merck; Financial Interests, Institutional, Sponsor/Funding: Celltrion; Non-Financial Interests, Personal, Officer: Translational Breast Cancer Research Consortium. D. Medgyesy: Financial Interests, Institutional, Sponsor/Funding: Seagen. J. Abraham: Financial Interests, Institutional, Sponsor/Funding: Seagen; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Non-Financial Interests, Personal, Other, Deputy Editor: JCO Oncology Practice; Non-Financial Interests, Personal, Other, Vice Chair Research Strategy: NRG Oncology; Non-Financial Interests, Personal, Advisory Board: NSABP; Non-Financial Interests, Personal, Principal Investigator: NSABP- DESTINY 05 Clinical Trial . S. Modi: Financial Interests, Personal, Invited Speaker: Genentech; Financial Interests, Personal, Invited Speaker: Daiichi/Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Macrogenics; Financial Interests, Institutional, Sponsor/Funding: Genentech; Financial Interests, Institutional, Sponsor/Funding: Daiichi/Sankyo; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: Seagen. H. Li: Financial Interests, Personal, Full or part-time Employment: Seagen. S. Wu: Financial Interests, Personal, Full or part-time Employment: Seagen. P.M. Garfin: Financial Interests, Personal, Full or part-time Employment: Seagen; Financial Interests, Personal, Stocks/Shares: Zymeworks; Financial Interests, Personal, Stocks/Shares: Mesoblast; Financial Interests, Personal, Stocks/Shares: Neoleukin. H.A. Burris III: Financial Interests, Personal, Full or part-time Employment: HCA Healthcare/Sarah Cannon Research Institute; Financial Interests, Personal, Stocks/Shares: HCA Healthcare/Sarah Cannon Research Institute; Financial Interests, Institutional, Sponsor/Funding: Genentech/Roche; Financial Interests, Institutional, Sponsor/Funding: Bristol Myers Squibb; Financial Interests, Institutional, Sponsor/Funding: Incyte; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: MedImmune; Financial Interests, Institutional, Sponsor/Funding: Macrogenics; Financial Interests, Institutional, Sponsor/Funding: Novartis; Financial Interests, Institutional, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Institutional, Sponsor/Funding: Lilly; Financial Interests, Institutional, Sponsor/Funding: Seagen; Financial Interests, Institutional, Sponsor/Funding: Merck; Financial Interests, Institutional, Sponsor/Funding: Agios; Financial Interests, Institutional, Sponsor/Funding: Jounce Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Moderna Therapeutics; Financial Interests, Institutional, Sponsor/Funding: CytomX Therapeutics; Financial Interests, Institutional, Sponsor/Funding: GlaxoSmithKline; Financial Interests, Institutional, Sponsor/Funding: Verastem; Financial Interests, Institutional, Sponsor/Funding: Tersaro; Financial Interests, Institutional, Sponsor/Funding: BioMed Valley Discoveries; Financial Interests, Institutional, Sponsor/Funding: TG Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Vertex; Financial Interests, Institutional, Sponsor/Funding: eFFECTOR; Financial Interests, Institutional, Sponsor/Funding: Janssen; Financial Interests, Institutional, Sponsor/Funding: Gilead Sciences; Financial Interests, Institutional, Sponsor/Funding: BioAtla; Financial Interests, Institutional, Sponsor/Funding: CicloMed; Financial Interests, Institutional, Sponsor/Funding: Harpoon Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Arch; Financial Interests, Institutional, Sponsor/Funding: Arvinas; Financial Interests, Institutional, Sponsor/Funding: Revolution Medicines; Financial Interests, Institutional, Sponsor/Funding: Array BioPharma; Financial Interests, Institutional, Sponsor/Funding: Bayer; Financial Interests, Institutional, Sponsor/Funding: BIND Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Kymab; Financial Interests, Institutional, Sponsor/Funding: miRNA Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: Takeda/Millenium; Financial Interests, Institutional, Sponsor/Funding: Foundation Medicine; Financial Interests, Institutional, Sponsor/Funding: EMD Serono; Non-Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Non-Financial Interests, Personal, Advisory Role: Pfizer; Non-Financial Interests, Personal, Advisory Role: Bayer; Non-Financial Interests, Personal, Advisory Role: GRAIL; Non-Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Advisory Role: Vincerx Pharma; Non-Financial Interests, Personal, Advisory Role: AstraZeneca; Non-Financial Interests, Personal, Advisory Role: FORMA Therapeutics; Non-Financial Interests, Personal, Advisory Role: Celgene; Non-Financial Interests, Personal, Advisory Role: Incyte; Non-Financial Interests, Personal, Member of the Board of Directors: ASCO. All other authors have declared no conflicts of interest.

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