Advanced Breast Cancer, Breast Cancer, Breast Cancer Female, Breast Neoplasm, Carcinoma, Ductal, Breast, Metastatic Breast Cancer, Stage IV Breast Cancer
Conditions
Keywords
Breast Cancer, Oral SERD, SERD, HER2-Negative, ER-Positive, ER+, HER2-, HER2 -ve, ER +ve, CDK 4/6 Inhibitor, Rintodestrant, G1T48
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.
Interventions
DRUGG1T48
oral SERD
DRUGPalbociclib
CDK 4/6 Inhibitor
Sponsors
G1 Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 dose | 12 months | G1T48 alone and in combination with palbociclib; progression-free survival (PFS) |
| Dose Limiting Toxicity | Cycle 1 Day -3 to Cycle 1 Day 28 | — |
| Number of Treatment Related Adverse Event, including Abnormal Laboratory Events | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | — |
| Tumor response based on RECIST, Version 1.1 | 21 months | G1T48 alone and in combination with palbociclib; |
| Pharmacokinetics of palbociclib: Plasma - Trough concentration | Part 3, Cycle 2 Day 1 to Cycle 3 Day 1. | — |
| Pharmacokinetics of G1T48 and metabolites: Plasma - Volume of distribution | 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. | — |
| 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. | — |
Countries
Belgium, Bulgaria, Georgia, Moldova, Netherlands, Ukraine, United States
Outcome results
None listed