CClinicalTrials.gg
CompletedNCT03455270Updated Sep 21, 2026

G1T48, an Oral SERD, Alone and in Combination With Palbociclib in ER-Positive, HER2-Negative Advanced Breast Cancer

A Phase 1 interventional study of G1T48 and Palbociclib in Carcinoma, Ductal, Breast, Breast Cancer Female and Breast Neoplasm, sponsored by G1 Therapeutics, Inc.. Completed at 15 sites in 7 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-21.

Sponsored by G1 Therapeutics, Inc. · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
107
Allocation
Non-randomized
Ages
18 Years and older
Sex
Female
01

Study summary

This is a study to investigate the potential clinical benefit of G1T48 as an oral selective estrogen receptor degrader (SERD) alone and in combination with palbociclib, a cyclin dependent kinase 4/6 (CDK 4/6) inhibitor, in patients with estrogen receptor-positive, HER2-negative metastatic breast cancer.

The study is an open-label design, consisting of 3 parts: dose-finding portion including food effect (Part 1), G1T48 monotherapy expansion portion (Part 2), and G1T48 in combination with palbociclib expansion portion (Part 3). All parts include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit. Approximately, 184 patients may be enrolled in the study.

02

Conditions studied

  • Carcinoma, Ductal, Breast
  • Breast Cancer Female
  • Breast Neoplasm
  • Breast Cancer
  • Metastatic Breast Cancer
  • Advanced Breast Cancer
  • Stage IV Breast Cancer

Keywords

  • Breast Cancer
  • Oral SERD
  • SERD
  • HER2-Negative
  • ER-Positive
  • ER+
  • HER2-
  • HER2 -ve
  • ER +ve
  • CDK 4/6 Inhibitor
  • Rintodestrant
  • G1T48
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • For Part 1, postmenopausal women only
  • For Parts 2 and 3, any menopausal status
  • Confirmed diagnosis of ER-positive, HER2-negative advanced breast cancer, not amenable to curative therapy
  • For Part 1, prior treatment with less than 4 prior lines of chemotherapy
  • For Part 2, prior treatment with less than 2 prior line of chemotherapy
  • For Part 3, prior treatment with no more than 1 prior line of chemotherapy
  • For Parts 1 and 2, prior treatment with less than 4 prior endocrine therapies for metastatic breast cancer
  • For Part 3, prior treatment with no more than 1 prior line of endocrine therapies for metastatic breast cancer
  • For Parts 1 and 2, patients must satisfy 1 of the following criteria for prior therapy:

    • Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor
    • Progressed after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer
  • For Part 3, patients must satisfy 1 of the following criteria for prior therapy:

    • Received ≥ 24 months of endocrine therapy in the adjuvant setting prior to recurrence or progression
    • Received ≥ 6 months of endocrine therapy in the advanced/metastatic setting prior to progression
  • For Part 1, evaluable or measurable disease
  • For Parts 2 and 3, evaluable (approximately 25%) or measurable disease (approximately 75%) as defined by RECIST, Version 1.1 including bone-only disease
  • ECOG performance status 0 to 1
  • Adequate organ function

Exclusion criteria

Exclusion Criteria:

  • For Part 3, prior treatment with CDK4/6 inhibitor, investigational oral SERDs or SERCAs in any setting
  • Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
  • Anticancer therapy within 14 days of first G1T48 dose or within 28 days for antibody-based therapy
  • Concurrent radiotherapy, radiotherapy within 14 days of first G1T48 dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow
  • Prior hematopoietic stem cell or bone marrow transplantation
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
107 participants (actual)

Study arms

  • Experimental
    Part 1: Dose Escalation (G1T48)

    Patients in Part 1 will receive a single oral dose of G1T48 on Cycle 1 Day -3 and will begin once-daily dosing on Cycle 1 Day 1. The initial dose cohort shall receive an identified starting dose and subsequent cohorts shall receive higher doses based on the safety and PK (pharmacokinetic(s)) data obtained from the previous dose levels.

    Drug: G1T48

  • Experimental
    Part 1: Food Effect Cohort (G1T48)

    In Part 1, additional G1T48 cohort(s) of 8 patients may be enrolled to assess the effect of different fat content meals (eg, high fat, moderate fat, or low-fat) on the rate and extent of the absorption of G1T48. Patients will receive a single oral dose of G1T48 on Cycle 1 Day -10 and on Cycle 1 Day -3. Patients will begin G1T48 once-daily dosing on Cycle 1 Day 1.

    Drug: G1T48

  • Experimental
    Part 2: Monotherapy Dose Expansion (G1T48)

    Patients in Part 2 will receive G1T48 once-daily at the dose determined in Part 1.

    Drug: G1T48

  • Experimental
    Part 3: Combination Dose Expansion (G1T48+palbociclib)

    Patients in Part 3 will receive G1T48 once-daily at the dose determined in Part 2 in combination with palbociclib once-daily on Days 1 to 21 of each 28-day cycle.

    Drug: G1T48 · Drug: Palbociclib

Interventions

  • DrugG1T48

    oral SERD

    Also known as: Rintodestrant

  • DrugPalbociclib

    CDK 4/6 Inhibitor

    Also known as: Ibrance

05

What researchers measure

Primary outcomes

  1. Dose Limiting Toxicity

    Time frame: Cycle 1 Day -3 to Cycle 1 Day 28

  2. Recommended Phase 2 dose

    G1T48 alone and in combination with palbociclib; progression-free survival (PFS)

    Time frame: 12 months

  3. Number of Treatment Related Adverse Event, including Abnormal Laboratory Events

    All AEs, including clinical laboratory, vitals signs, physical examinations and ECGs will be analyzed in all patients receiving study drug(s) from the signing of the informed consent until 30 days after the last dose of study medication(s).

    Time frame: 21 months

Secondary outcomes

  1. Tumor response based on RECIST, Version 1.1

    G1T48 alone and in combination with palbociclib;

    Time frame: 21 months

  2. Effect of food on bioavailability of G1T48

    Time frame: Part 1, Cycle 1 Day -10 to Cycle 1 Day 1.

  3. Pharmacokinetics of G1T48 and metabolites: Maximum Plasma Concentration (Cmax)

    Time frame: Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1. Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.

  4. Pharmacokinetics of G1T48 and metabolites: Area under Curve - plasma concentration (AUC)

    Time frame: Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1. Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.

  5. Pharmacokinetics of G1T48 and metabolites: Plasma: terminal half life (T1/2)

    Time frame: Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1. Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.

  6. Pharmacokinetics of G1T48 and metabolites: Plasma - Volume of distribution

    Time frame: Part 1, Cycle 1 Day -3 to Cycle 2 Day 1. Part 2, Cycle 2 Day 1 to Cycle 3 Day 1. Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.

  7. Pharmacokinetics of palbociclib: Plasma - Trough concentration

    Time frame: Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.

06

Study locations

15 sites
  • Beverly Hills Cancer Center
    Beverly Hills, California 90211, United States
  • Stanford Women Cancer Center
    Stanford, California 94305, United States
  • Northwestern University - Feinberg School of Medicine
    Chicago, Illinois 60611, United States
  • University of North Carolina at Chapel Hill
    Chapel Hill, North Carolina 27599-7305, United States
  • Stephenson Cancer Center
    Oklahoma City, Oklahoma 73104, United States
  • Sarah Cannon Research Institute at Tennessee Oncology
    Nashville, Tennessee 37203, United States
  • Institut Jules Bordet
    Brussels, 1000, Belgium
  • UZ Leuven
    Leuven, 3000, Belgium
  • MHAT for Womens Health - Nadezhda OOD
    Sofia, 1330, Bulgaria
  • ARENSIA Exploratory Medicine LLC
    Tbilisi, 0112, Georgia
  • ARENSIA Exploratory Medicine Phase I Unit, The Institute of Oncology
    Chisinau, 2025, Moldova
  • VU University Medical Center
    Amsterdam, 1081 HV, Netherlands
  • University Medical Center Groningen
    Groningen, 9713 GZ, Netherlands
  • Erasmus Medical Center
    Rotterdam, 3015 GD, Netherlands
  • Spizhenko Clinic
    Kiev, 08112, Ukraine
07

Registry details

Key details

Study ID
NCT03455270
Lead sponsor
G1 Therapeutics, Inc.
Responsible party
Sponsor
First posted
Mar 6, 2018
Start date
May 9, 2018
Primary completion
Sep 29, 2022
Completion
Sep 29, 2022
Last update
Sep 21, 2026

Study contacts

Clinical Contact
study director · G1 Therapeutics, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion