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

NCT03455270 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: G1T48-012017-004502-17
• Study Type: interventional
• Target: 107
• Locations: 7 countries
• Sites: 15

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

Outcome Measures

Primary Outcomes (3)

• Dose Limiting Toxicity

  Cycle 1 Day -3 to Cycle 1 Day 28

• Recommended Phase 2 dose

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

  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).

  21 months

Secondary Outcomes (7)

• Tumor response based on RECIST, Version 1.1

  21 months

• Effect of food on bioavailability of G1T48

  Part 1, Cycle 1 Day -10 to Cycle 1 Day 1.

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

  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)

  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)

  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.

Study Arms (4)

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 data obtained from the previous dose levels.

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.

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.

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.

Drug: G1T48; Drug: Palbociclib

Interventions

G1T48 DRUG

oral SERD

Also known as: Rintodestrant

Part 1: Dose Escalation (G1T48); Part 1: Food Effect Cohort (G1T48); Part 2: Monotherapy Dose Expansion (G1T48); Part 3: Combination Dose Expansion (G1T48+palbociclib)

Palbociclib DRUG

CDK 4/6 Inhibitor

Also known as: Ibrance

Part 3: Combination Dose Expansion (G1T48+palbociclib)

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• G1 Therapeutics, Inc.: lead

Study Sites (15)

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

Stanford Women Cancer Center

Stanford, California, 94305, United States

Location

Northwestern University - Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7305, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

MHAT for Womens Health - Nadezhda OOD

Sofia, 1330, Bulgaria

Location

ARENSIA Exploratory Medicine LLC

Tbilisi, 0112, Georgia

Location

ARENSIA Exploratory Medicine Phase I Unit, The Institute of Oncology

Chisinau, 2025, Moldova

Location

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3015 GD, Netherlands

Location

Spizhenko Clinic

Kiev, 08112, Ukraine

Location

MeSH Terms

Conditions

Carcinoma, Ductal, Breast; Breast Neoplasms

Interventions

palbociclib

Condition Hierarchy (Ancestors)

Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Clinical Contact

  G1 Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2018
• First Posted: March 6, 2018
• Study Start: May 9, 2018
• Primary Completion: September 29, 2022
• Study Completion: September 29, 2022
• Last Updated: December 15, 2022

Record last verified: 2022-12

Locations

UA (1); GE (1); US (6); MO (1); BE (2); BU (1); NL (3)