Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Gemcitabine and Carboplatin for Metastatic Triple-Negative Breast Cancer (TNBC)

This study will have two separate cohorts (Cohort 1 and Cohort 2). Both cohorts will follow the same general study conduct/design with similar primary and key secondary endpoints and identical treatment arms.

• Cohort 1 will evaluate patients receiving first-line therapy, regardless of programmed death-ligand 1 (PD-L1) status, who are programmed cell death protein 1 (PD-1)/PD-L1 inhibitor therapy naïve.
• Cohort 2 will evaluate PD-L1 positive patients receiving second-line therapy following prior PD-1/PD-L1 inhibitor therapy in the locally advanced unresectable/metastatic setting.

Inclusion criteria

• Age >/= 18 years of age with evaluable locally advanced unresectable or metastatic TNBC.
• Documentation of triple negative breast cancer (estrogen and progesterone receptor <1% and HER2-negative)
• Prior systemic therapies (Cohort 1 only):

• No prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, targeted therapy, immunotherapy, or investigational agents.
• Prior PD-1/PD-L1 inhibitor treatment is not permitted in any setting, including in the neoadjuvant setting.
• Time between completion of last treatment with curative intent and first metastatic recurrence must be ≥ 6 months.
• Prior systemic therapies (Cohort 2 only):

• Documentation of PD-L1 positive status
• Treated with a PD-1/PD-L1 inhibitor for a minimum duration of 4 months in the locally advanced unresectable/metastatic setting and as the most recent therapy.
• Radiation therapy for metastatic disease is permitted. There is no required minimum washout period for radiation therapy. Patients should be recovered from the effects of radiation.
• Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function as demonstrated by normal laboratory values

Exclusion criteria

• Prior treatment with gemcitabine in any setting.
• Prior treatment with carboplatin in the locally advanced unresectable/metastatic setting.

Prior carboplatin in the (neo)adjuvant/curative setting is permitted as long as it was completed ≥ 6 months prior to the first metastatic recurrence.

• Presence of central nervous system (CNS) metastases and/or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
• Receipt of any cytotoxic chemotherapy within 14 days prior to the first dose of study drugs.
• QTcF interval >480 msec at Screening (confirmed in triplicate). For patients with ventricular pacemakers, QTcF >500 msec.
• Known hypersensitivity to carboplatin or other platinum-containing compounds, or mannitol
• Pregnant or lactating women
• Prior hematopoietic stem cell or bone marrow transplantation