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Breast cancer, metastatic

1419 - Initial results of a phase 1 dose expansion cohort of VX-970, a first-in-class ATR inhibitor, in combination with cisplatin (Cis) in patients (pts) with metastatic triple-negative breast cancer (mTNBC) (NCT02157792)

Date

10 Sep 2017

Session

Breast cancer, metastatic

Presenters

Melinda Telli

Citation

Annals of Oncology (2017) 28 (suppl_5): v74-v108. 10.1093/annonc/mdx365

Authors

M.L. Telli1, S. Lord2, E. Dean3, V. Abramson4, H. Arkenau5, C. Becerra6, S.M. Tolaney7, R. Tang8, M.S. Penney8, J. Pollard9, G. Conboy8, S.Z. Fields8, G. Shapiro7

Author affiliations

  • 1 Oncology, Stanford University School of Medicine, 94305 - Stanford/US
  • 2 Department Of Oncology, Churchill Hospital, University of Oxford, OX3 7LE - Oxford/GB
  • 3 Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 4 Division Of Hematology, Vanderbilt University Medical Center, 37232 - Nashville/US
  • 5 Oncology, Sarah Cannon Research Institute SCRI UK, W1G 6AD - London/GB
  • 6 Baylor Charles A. Sammons Cancer Center, Texas Oncology, 75246 - Dallas/US
  • 7 Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 8 Oncology, Vertex Pharmaceuticals Incorporated, 02210 - Boston/US
  • 9 Oncology, Vertex Pharmaceuticals Limited, OX14 4RY - Oxford/GB
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Resources

Abstract 1419

Background

ATR is a regulator of the cellular response to replication stress and signals DNA damage repair through homologous recombination. Many cancers depend on ATR to survive DNA damage. VX-970 is a potent, selective inhibitor of ATR with preclinical anticancer activity in combination with DNA-damaging chemotherapy in TNBC models. Given the prevalence of DNA damage repair defects in TNBC, this study evaluated the safety and efficacy of VX-970 in combination with Cis in an expansion cohort of pts with BRCA1/2 wild-type mTNBC.

Methods

Eligible pts had advanced ER-, PR-, and HER2- BC with 0-2 prior non–platinum-based therapies. First line pts were eligible if relapse occurred ≥ 3 months after prior (neo)adjuvant chemotherapy. Measurable disease per RECIST 1.1 was required. Of a maximum 50 pts planned for enrollment, ≥30 were required to be BRCA1/2 germline wild-type and to have basaloid molecular subtype tumors on central testing. Pts received intravenous Cis 75 mg/m2 on day 1 with VX-970 140 mg/m2 on days 2 and 9 of each 21-day cycle. In pts intolerant to Cis or at investigator’s discretion, treatment could be switched to carboplatin AUC 5 with VX-970 90 mg/m2.

Results

At the time of this analysis, 35 female pts with mTNBC who received ≥1 cycle of study drug were included in the safety set (median age, 48 y [range 35-74 y]). Grade ≥3 related TEAEs occurred in 16/35 pts: neutropenia (n = 8), anemia (n = 5), vomiting (n = 4), nausea (n = 3), and 1 pt each with thrombocytopenia, neutrophil count decreased, platelet count decreased, hypokalemia, generalized weakness, rigors, and acute kidney injury. Of these 35 pts, 18 were BRCA1/2 wild-type and had basaloid TNBC with at least 1 baseline scan and 1 on-treatment scan at the time of the data cut. Preliminary objective response rate was 38.9% (n = 7 [all partial response]), and disease control rate (CR+PR+SD) was 72.2% (n = 13).

Conclusions

Combination VX-970 and Cis shows encouraging antitumor activity and tolerability in mTNBC. The study is ongoing; updated safety and efficacy results will be presented.

Clinical trial identification

NCT02157792

Legal entity responsible for the study

Vertex Pharmaceuticals Incorporated

Funding

Vertex Pharmaceuticals Incorporated

Disclosure

M.L. Telli: Advisory role for AstraZeneca, PharmaMar, Tesaro, and Vertex, and contracted research with Calithera, Genentech, Medivation, Novartis, OncoSec, Pfizer, PharmaMar, Tesaro, and Vertex. E. Dean: Employee of AstraZeneca. Research funding from Vertex. S.M. Tolaney: Research funding from Genentech, Merck, Pfizer, Novartis, Lilly, Exelixis, Nektar, and AstraZeneca. R. Tang, M.S. Penney, G. Conboy, S.Z. Fields: Employee of Vertex Pharmaceuticals Incorporated and may own stock or stock options in that company. J. Pollard: Employee of Vertex Pharmaceuticals Limited and may own stock or stock options in that company. G. Shapiro: Research funding from Vertex and Pfizer. Advisory role for Vertex, G1 Therapeutics, Lilly, Millenium/Takeda, Tesaro, Chugai, and EMD Serono. All other authors have declared no conflicts of interest.

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