Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 2

3587 - Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC)

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Breast Cancer

Presenters

E Dees

Citation

Annals of Oncology (2019) 30 (suppl_5): v104-v142. 10.1093/annonc/mdz242

Authors

E.C. Dees1, P.G. Aftimos2, C.W. Menke-van der Houven van Oordt3, E.G..E. De Vries4, P. Neven5, M.D. Pegram6, R. Iqbal3, J. Boers4, J. Xiao7, C. Sipes8, C. Li9, J.A. Sorrentino10, R. Malik11, A.P. Beelen12

Author affiliations

  • 1 Hematology And Oncology, UNC Lineberger Comprehensive Cancer Center, 27715 - Chapel Hill/US
  • 2 Clinical Trials Conduct Unit, Institute Jules Bordet, 1000 - Brussels/BE
  • 3 Medical Oncology, Vrije University Medical Centre (VUMC), 1081 HV - Amsterdam/NL
  • 4 Medical Oncology, University Hospital Groningen (UMCG), 9700 RB - Groningen/NL
  • 5 Vesalius Research Center - Vib, University Hospitals Leuven, Ku Leuven, University of Leuven, 3000 - Leuven/BE
  • 6 Medicine, Stanford Comprehensive Cancer Institute, 94305-545 - Stanford/US
  • 7 Biometrics, G1 Therapeutics, Inc, NC 27709 - Research Triangle Park/US
  • 8 Clinical Operations, G1 Therapeutics, Inc, NC 27709 - Research Triangle Park/US
  • 9 Clinical Pharmacology, Clinical Development, G1 Therapeutics, Inc, NC 27709 - Research Triangle Park/US
  • 10 Biomarkers, Clinical Development, G1 Therapeutics, Inc, NC 27709 - Research Triangle Park/US
  • 11 Research And Development, G1 Therapeutics, Inc, NC 27709 - Research Triangle Park/US
  • 12 Clinical Development, G1 Therapeutics, Inc, NC 27709 - Research Triangle Park/US

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 3587

Background

The SERD fulvestrant is a well-established therapy for ER+/HER2- ABC. However, its intramuscular route of administration may be painful and limits systemic exposure. G1T48 is a highly potent and efficacious oral SERD in both mutant and WT ESR1 preclinical models with the potential to achieve higher exposure and provide clinical benefit in patients with ER+ ABC.

Methods

Postmenopausal women with ER+/HER2- ABC following progression on endocrine therapy are eligible for this 3 + 3 dose escalation and expansion study. Patients receive G1T48 QD until disease progression or unacceptable toxicity. The objectives are to evaluate DLTs, safety, tolerability, PK, ER target engagement via [18F] FES-PET, and anti-tumor efficacy, and to determine the recommended phase 2 dose.

Results

Currently, 11 patients (mean age 64 years) have received G1T48 doses ranging from 200-800 mg QD for up to 7 months. Prior lines (median of 3) included chemotherapy in 45%, fulvestrant in 91%, and CDK4/6i in 54% of patients. G1T48 is well tolerated: no DLTs, G1T48-related SAEs, or withdrawals due to an AE have occurred. The most common Gr 1/2 G1T48-related TEAEs are diarrhea, headache, hot flush, and nausea (27% each) with a single Gr 3 TEAE (fatigue) and no Gr 4 TEAEs. G1T48 exposure increased with dose (200 to 800 mg), and minimum to moderate accumulation of G1T48 was observed following repeated doses. Median maximum standard tumor [18F] FES-PET uptake values decreased (ranging from 70% (200 mg) to 88% (600 mg)) after 4 weeks of treatment. Of 6 response evaluable patients (RECIST v1.1), 1 patient had a PR (600 mg, prior palbociclib/fulvestrant) and 1 patient had SD ≥ 24 weeks (200 mg, prior abemaciclib/fulvestrant).

Conclusions

The oral SERD G1T48 is well tolerated with no DLTs reported to date in patients with ER+/HER2- ABC. Early efficacy, safety, PK, and FES-PET data are encouraging, and support continued dose escalation followed by expansion. Updated safety, anti-tumor activity, and cfDNA data will be presented (NCT#03455270).

Clinical trial identification

NCT03455270.

Editorial acknowledgement

Legal entity responsible for the study

G1 Therapeutics, Inc.

Funding

G1 Therapeutics.

Disclosure

E.C. Dees: Research grant / Funding (institution): G1 Therapeutics; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Merck; Research grant / Funding (institution): H3Biosciences; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Cerulean; Research grant / Funding (institution): Meryx; Advisory / Consultancy, Research grant / Funding (institution): Novartis. P.G. Aftimos: Advisory / Consultancy: Boehringer Ingleheim; Advisory / Consultancy: Macrogenics; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Amcure; Honoraria (self), Research grant / Funding (institution): Synthon; Honoraria (self), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Radius; Research grant / Funding (institution): Servier. C.W. Menke-van der Houven van Oordt: Advisory / Consultancy: G1 Therapeutics; Advisory / Consultancy: Novartis. E.G..E. De Vries: Research grant / Funding (institution): G1 Therapeutics; Advisory / Consultancy: NSABP; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Chugai; Research grant / Funding (institution): CytomX Therapeutics; Research grant / Funding (institution): Nordic Nanovector; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Synthon. M.D. Pegram: Advisory / Consultancy: G1 Therapeutics. J. Xiao: Full / Part-time employment: G1 Therapeutics. C. Sipes: Full / Part-time employment: G1 Therapeutics. C. Li: Full / Part-time employment: G1 Therapeutics. J.A. Sorrentino: Full / Part-time employment: G1 Therapeutics. R. Malik: Full / Part-time employment: G1 Therapeutics. A.P. Beelen: Full / Part-time employment: G1 Therapeutics. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.