Carcinoma, Ductal, BreastPhase 1NCT03455270
G1T48, an Oral SERD, Alone and in Combination With Palbociclib in ER-Positive, HER2-Negative Advanced Breast Cancer
A Phase 1 study testing G1T48 and Palbociclib in people with Carcinoma, Ductal, Breast and Breast Cancer Female, run by G1 Therapeutics, Inc. at 15 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Carcinoma, Ductal, Breast, Breast Cancer Female, Breast Neoplasm
- What is being tested?
- G1T48 and Palbociclib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 15 sitesin 7 countries
- Study dates
- 9 May 2018to 29 Sep 2022
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
15 sites in 7 countries.
15 sites in 7 countries
United States6 sites
Beverly Hills Cancer Center
Beverly Hills, California, 90211
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599-7305
Northwestern University - Feinberg School of Medicine
Chicago, Illinois, 60611
Sarah Cannon Research Institute at Tennessee Oncology
Nashville, Tennessee, 37203
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Stanford Women Cancer Center
Stanford, California, 94305
Netherlands3 sites
VU University Medical Center
Amsterdam, 1081 HV
University Medical Center Groningen
Groningen, 9713 GZ
Erasmus Medical Center
Rotterdam, 3015 GD
Moldova1 site
ARENSIA Exploratory Medicine Phase I Unit, The Institute of Oncology
Chisinau, 2025
About this study
Official title: A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Ascending Doses of G1T48 Alone and in Combination With Palbociclib in Women With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer
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.
- Conditions
- Carcinoma, Ductal, Breast, Breast Cancer Female, Breast Neoplasm, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer
- Being tested
- G1T48, Palbociclib
- Keywords
- Breast Cancer, Oral SERD, SERD, HER2-Negative, ER-Positive, ER+, HER2-, HER2 -ve, ER +ve, CDK 4/6 Inhibitor, Rintodestrant, G1T48
- Medical subject headings
- Carcinoma, Ductal, Breast, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
G1T48Drug
Also called Rintodestrant
oral SERD
PalbociclibDrug
Also called Ibrance
CDK 4/6 Inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Dose Escalation (G1T48) | Experimental | 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. Receives: Drug: G1T48 |
| Part 1: Food Effect Cohort (G1T48) | Experimental | 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. Receives: Drug: G1T48 |
| Part 2: Monotherapy Dose Expansion (G1T48) | Experimental | Patients in Part 2 will receive G1T48 once-daily at the dose determined in Part 1. Receives: Drug: G1T48 |
| Part 3: Combination Dose Expansion (G1T48+palbociclib) | Experimental | 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. Receives: Drug: G1T48; Drug: Palbociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity
Measured: Cycle 1 Day -3 to Cycle 1 Day 28
Recommended Phase 2 dose
G1T48 alone and in combination with palbociclib; progression-free survival (PFS)
Measured: 12 months
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).
Measured: 21 months
Secondary outcomes (7)
Tumor response based on RECIST, Version 1.1
G1T48 alone and in combination with palbociclib;
Measured: 21 months
Effect of food on bioavailability of G1T48
Measured: Part 1, Cycle 1 Day -10 to Cycle 1 Day 1.
Pharmacokinetics of G1T48 and metabolites: Maximum Plasma Concentration (Cmax)
Measured: 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.
Pharmacokinetics of G1T48 and metabolites: Area under Curve - plasma concentration (AUC)
Measured: 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.
Pharmacokinetics of G1T48 and metabolites: Plasma: terminal half life (T1/2)
Measured: 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.
Pharmacokinetics of G1T48 and metabolites: Plasma - Volume of distribution
Measured: 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.
Pharmacokinetics of palbociclib: Plasma - Trough concentration
Measured: Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2018
- Study start9 May 2018
- Primary completion29 Sep 2022
- Study completion29 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Ductal, BreastStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- G1 Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Contact, Study director, G1 Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03455270
- Sponsor's protocol ID
- G1T48-01
- Other IDs
- 2017-004502-17, 2017
- Status last verified
- Sep 2026
- First submitted
- 28 Feb 2018
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No