Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Gemcitabine and Carboplatin in Metastatic Triple Negative Breast Cancer (mTNBC)

G1 Therapeutics

Status and phase: Terminated; Phase 2

Conditions: Breast Cancer; Breast Neoplasm; Triple-Negative Breast Neoplasms; Triple-Negative Breast Cancer

Treatments: Drug: Gemcitabine; Drug: Carboplatin; Drug: Trilaciclib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02978716

G1T28-04

2016-004466-26 (EudraCT Number)

Details and patient eligibility

About

This was a study to investigate the potential clinical benefit of trilaciclib (G1T28) in preserving the bone marrow and the immune system, and enhancing chemotherapy antitumor efficacy when administered prior to carboplatin and gemcitabine (GC therapy) for participants with metastatic triple negative breast cancer.

The study was an open-label and 102 participants were randomly assigned (1:1:1 fashion) to 1 of the 3 following treatment groups:

• Group 1: GC therapy (Days 1 and 8 of 21-day cycles) only (n=34)
• Group 2: GC therapy (Days 1 and 8) plus trilaciclib (G1T28) on Days 1 and 8 of 21-day cycles (n=33)
• Group 3: GC therapy (Days 2 and 9) plus trilaciclib (G1T28) on Days 1, 2, 8, and 9 of 21-day cycles (n=35)

The study included 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.

Full description

The posted results represent the final results of Study G1T28-04, a Phase 2 study of the safety, efficacy and pharmacokinetics of trilaciclib (G1T28) in patients with locally recurrent/metastatic triple negative breast cancer receiving gemcitabine and carboplatin chemotherapy.

The final myelopreservation efficacy results are reported from database lock 1 ([DBL1], data cut-off [DCO] date of 30 July 2018). Final anti-tumor efficacy (ORR, PFS), and final summary exposure and safety data are reported from database lock 2 ([DBL2], DCO 28 June 2019) which occurred to support filing of the trilaciclib New Drug Application (NDA). Final overall survival (OS) data are reported from the final database lock which occurred on 17 July 2020 (with a last patient last visit date of 28 February 2020).

Enrollment: 102 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Confirmed diagnosis of hormone receptor (HR)-negative, human epidermal growth factor receptor 2 (HER2)-negative (locally recurrent or metastatic TNBC) breast cancer
• Available TNBC diagnostic tumor tissue (archived tissue allowed)
• Evaluable disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Adequate organ function
• Predicted life expectancy of 3 or more months

Exclusion criteria

• More than 2 prior chemotherapy regimens for locally recurrent or metastatic TNBC. If > 12 months have elapsed between the date of last adjuvant/neoadjuvant chemotherapy administration and first documented local or distant disease recurrence the therapy will not be considered a line of therapy in the locally recurrent or metastatic TNBC setting.
• CNS metastases or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
• Investigational drug within 30 days of first trilaciclib (G1T28) dose
• Concurrent radiotherapy, radiotherapy within 14 days of first trilaciclib (G1T28) dose
• Cytotoxic chemotherapy within 3 weeks of first trilaciclib (G1T28) dose
• Prior hematopoietic stem cell or bone marrow transplantation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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102 participants in 3 patient groups

Group 1: Gemcitabine/Carboplatin (Days 1 and 8)

Experimental group

Description:

Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square \[mg/m\^2\] and carboplatin area under the curve \[AUC\] 2) on Days 1 and 8 of 21-day cycle. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).

Treatment:

Drug: Carboplatin

Drug: Gemcitabine

Group 2: Trilaciclib + Gemcitabine/ Carboplatin (Days 1 and 8)

Experimental group

Description:

Participants received IV infusion of trilaciclib 240 mg/m\^2 plus GC chemotherapy (gemcitabine 1000 mg/m\^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycle. Trilaciclib was administered prior to chemotherapy.

Treatment:

Drug: Trilaciclib

Drug: Carboplatin

Drug: Gemcitabine

Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)

Experimental group

Description:

Participants received IV infusion of trilaciclib 240 mg/m\^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m\^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day Cycle. Trilaciclib was administered prior to chemotherapy.

Treatment:

Drug: Trilaciclib

Drug: Carboplatin

Drug: Gemcitabine