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

NCT ID: NCT03455270

Last Updated: 2022-12-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-09
• Study Completion Date: 2022-09-29

Brief 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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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 data obtained from the previous dose levels.

Group Type: EXPERIMENTAL

G1T48

Intervention Type: DRUG

oral SERD

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.

Group Type: EXPERIMENTAL

G1T48

Intervention Type: DRUG

oral SERD

Part 2: Monotherapy Dose Expansion (G1T48)

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

Group Type: EXPERIMENTAL

G1T48

Intervention Type: DRUG

oral SERD

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.

Group Type: EXPERIMENTAL

G1T48

Intervention Type: DRUG

oral SERD

Palbociclib

Intervention Type: DRUG

CDK 4/6 Inhibitor

Interventions

G1T48

oral SERD

Intervention Type: DRUG

Palbociclib

CDK 4/6 Inhibitor

Intervention Type: DRUG

Other Intervention Names

Rintodestrant; Ibrance

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

G1 Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Contact

Role: STUDY_DIRECTOR

G1 Therapeutics, Inc.

Locations

Beverly Hills Cancer Center

Beverly Hills, California, United States

Stanford Women Cancer Center

Stanford, California, United States

Northwestern University - Feinberg School of Medicine

Chicago, Illinois, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, United States

Institut Jules Bordet

Brussels, , Belgium

UZ Leuven

Leuven, , Belgium

MHAT for Womens Health - Nadezhda OOD

Sofia, , Bulgaria

ARENSIA Exploratory Medicine LLC

Tbilisi, , Georgia

ARENSIA Exploratory Medicine Phase I Unit, The Institute of Oncology

Chisinau, , Moldova

VU University Medical Center

Amsterdam, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Erasmus Medical Center

Rotterdam, , Netherlands

Spizhenko Clinic

Kiev, , Ukraine

Countries

United States; Belgium; Bulgaria; Georgia; Moldova; Netherlands; Ukraine

Other Identifiers

2017-004502-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

G1T48-01

Identifier Type: -

Identifier Source: org_study_id