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

G1 Therapeutics

Status and phase: Completed; Phase 1

Conditions: Breast Cancer; Breast Neoplasm; Breast Cancer Female; Carcinoma, Ductal, Breast; Metastatic Breast Cancer; Stage IV Breast Cancer; Advanced Breast Cancer

Treatments: Drug: G1T48; Drug: Palbociclib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03455270

2017-004502-17 (EudraCT Number)

G1T48-01

Details and patient eligibility

About

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.

Enrollment: 107 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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107 participants in 4 patient groups

Part 1: Dose Escalation (G1T48)

Experimental group

Description:

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.

Treatment:

Drug: G1T48

Part 1: Food Effect Cohort (G1T48)

Experimental group

Description:

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.

Treatment:

Drug: G1T48

Part 2: Monotherapy Dose Expansion (G1T48)

Experimental group

Description:

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

Treatment:

Drug: G1T48

Part 3: Combination Dose Expansion (G1T48+palbociclib)

Experimental group

Description:

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.

Treatment:

Drug: Palbociclib

Drug: G1T48