Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Gemcitabine and Carboplatin for Metastatic Triple-Negative Breast Cancer (TNBC) (PRESERVE 2)

G1 Therapeutics

Status and phase: Active, not recruiting; Phase 3

Conditions: Breast Cancer; TNBC - Triple-Negative Breast Cancer

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04799249

2020-004930-39 (EudraCT Number)

G1T28-208

Details and patient eligibility

About

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of trilaciclib versus placebo administered prior to gemcitabine and carboplatin in patients receiving first- or second-line treatment for locally advanced unresectable/metastatic TNBC.

Full description

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.

Enrollment: 194 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age >/= 18 years of age with evaluable locally advanced unresectable or metastatic TNBC.

2. Documentation of triple negative breast cancer (estrogen and progesterone receptor <1% and HER2-negative)

3. Prior systemic therapies (Cohort 1 only):

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

4. Prior systemic therapies (Cohort 2 only):

   1. Documentation of PD-L1 positive status
   2. 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.

5. 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.

6. Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

8. Adequate organ function as demonstrated by normal laboratory values

Exclusion criteria

1. Prior treatment with gemcitabine in any setting.

2. 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.

3. Presence of central nervous system (CNS) metastases and/or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.

4. Receipt of any cytotoxic chemotherapy within 14 days prior to the first dose of study drugs.

5. QTcF interval >480 msec at Screening (confirmed in triplicate). For patients with ventricular pacemakers, QTcF >500 msec.

6. Known hypersensitivity to carboplatin or other platinum-containing compounds, or mannitol

7. Pregnant or lactating women

8. Prior hematopoietic stem cell or bone marrow transplantation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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194 participants in 2 patient groups, including a placebo group

Trilaciclib + gemcitabine + carboplatin

Experimental group

Description:

Trilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2)

Treatment:

Drug: Carboplatin

Drug: Gemcitabine

Drug: Trilaciclib

Placebo + gemcitabine + carboplatin

Placebo Comparator group

Description:

The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.

Treatment:

Drug: Carboplatin

Drug: Gemcitabine

Drug: Placebo