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
- Are there results?
- None posted in the registry
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
Show all 18Show fewer
- 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
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03455270
- Acronym / sponsor ID
- G1T48-01
- Conditions
- Carcinoma, Ductal, Breast, Breast Cancer Female, Breast Neoplasm, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer
- Keywords
- Breast Cancer, Oral SERD, SERD, HER2-Negative, ER-Positive, ER+, HER2-, HER2 -ve
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- G1 Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 9 May 2018 (actual)
- Primary completion
- 29 Sep 2022 (actual)
- Study completion
- 29 Sep 2022 (actual)
- First posted
- 6 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1: Dose Escalation (G1T48) | Experimental | Drug: G1T48Patients 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. |
| Part 1: Food Effect Cohort (G1T48) | Experimental | Drug: G1T48In 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. |
| Part 2: Monotherapy Dose Expansion (G1T48) | Experimental | Drug: G1T48Patients in Part 2 will receive G1T48 once-daily at the dose determined in Part 1. |
| Part 3: Combination Dose Expansion (G1T48+palbociclib) | Experimental | Drug: G1T48, Drug: PalbociclibPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| G1T48Also: Rintodestrantoral SERD | Drug | Part 1: Dose Escalation (G1T48), Part 1: Food Effect Cohort (G1T48), Part 2: Monotherapy Dose Expansion (G1T48), Part 3: Combination Dose Expansion (G1T48+palbociclib) |
| PalbociclibAlso: IbranceCDK 4/6 Inhibitor | Drug | Part 3: Combination Dose Expansion (G1T48+palbociclib) |
Primary outcome
Dose Limiting Toxicity
Time frame: Cycle 1 Day -3 to Cycle 1 Day 28
Recommended Phase 2 dose
Time frame: 12 months
G1T48 alone and in combination with palbociclib; progression-free survival (PFS)
Number of Treatment Related Adverse Event, including Abnormal Laboratory Events
Time frame: 21 months
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).
7 secondary outcomes
Tumor response based on RECIST, Version 1.1
Time frame: 21 months
Effect of food on bioavailability of G1T48
Time frame: Part 1, Cycle 1 Day -10 to Cycle 1 Day 1.
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.
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.
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.
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.
Pharmacokinetics of palbociclib: Plasma - Trough concentration
Time frame: Part 3, Cycle 2 Day 1 to Cycle 3 Day 1.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Contact study director
G1 Therapeutics, Inc.
15 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Netherlands, Belgium, Bulgaria, Georgia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (time frame: Cycle 1 Day -3 to Cycle 1 Day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.