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

Phase 1

• Conditions: ocally Advanced Unresectable or Metastatic Triple Negative Breast Cancer; MedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: LLTClassification code 10084066Term: Triple negative breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10072740Term: Locally advanced breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004930-39-ES
• Lead Sponsor: G1 Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-01
• Last Update Posted: 14 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

1. Female or male patients with evaluable locally advanced unresectable or metastatic TNBC
2. Age >/=18 years
3. Histological or cytological confirmation of hormone (estrogen and progesterone) receptor negative tumor by immunohistochemistry (IHC) assessment (defined as <1% nuclei staining) and HER2-negative, non-overexpressing (by IHC [0 or 1+] OR in situ hybridization [ratio <2.0] OR average HER2 gene copy number of <4 signals/nucleus) per 2018 American Society of Clinical Oncology and the College of American Pathologists (ASCO CAP) criteria.
4. Prior systemic therapies (Cohort 1):
a. No prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, targeted therapy, immunotherapy, or investigational agents.
b. Prior PD-1/PD-L1 inhibitor treatment is not permitted in any setting, including in the neoadjuvant setting.
c. Time between completion of last treatment with curative intent and first metastatic recurrence must be >/= 6 months.
d. Only patients for whom treatment with a PD-1/PD-L1 inhibitor is not an option, either based on clinical eligibility or drug availability, will be enrolled in Cohort 1.
5. Prior systemic therapies (Cohort 2):
a. Documentation of PD-L1 positive status
b. 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. Washout of at least 14 days from prior PD-1/PD L1 inhibitor to the first dose of study drug is required.
6. Radiation therapy for metastatic disease is permitted. There is no required minimum washout period for these therapies. Patients should be recovered from the effects of radiation.
7. Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor. If archival tissue is used, representative formalin-fixed paraffin embedded (FFPE) tumor specimens in paraffin blocks (75-micron) or at least 15 (5-micron) unstained slides are required.
a. For Cohort 1 only, some of the tumor tissue noted above will be used for determination of tumor PD-L1 status using the Ventana SP-142 IVD assay which can be assay locally or centrally. Testing should be conducted on a recurrent/metastatic tumor; however, a primary lesion is acceptable. Documentation of PD-L1 status is acceptable for randomization if testing was done using the Ventana SP-142 IVD assay.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
9. Adequate organ function as demonstrated by:
a. Hemoglobin >/=9.0 g/dL in the absence of RBC transfusion or ESA administration within 14 days prior to first dose of study drug
b. Absolute neutrophil count (ANC) >/=1.5 × 109/L
c. Platelet count >/=100 × 109/L
d. Estimated glomerular filtration rate >/=30 mL/minute/1.73 m2
e. Total bilirubin f. ALT and AST 10. Resolution of nonhematologic toxicities from prior systemic therapy, radiation therapy, or surgical procedures to 11. Predicted life expectancy of =3 months
12. Contraceptive use by men or women should be consistent with respective local regulations for those participating in clinical studies. Please see Section 17.3 for detailed required instructions
13. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed con

Exclusion Criteria

A patient will not be eligible for participation in this study if any of the following criteria apply:
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. Malignancies other than TNBC within 3 years prior to randomization: Patients with malignancies of a negligible risk of metastasis or death (e.g., risk of metastasis or death <5% at 5 years as determined by the investigator) are eligible provided they meet all of the following criteria:
a. Malignancy treated with expected curative intent (e.g., adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent)
b. No evidence of recurrence or metastasis by follow-up imaging and any disease-specific tumor markers
4. Presence of central nervous system (CNS) metastases and/or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids. Patient must be off steroids administered for brain metastases for at least 14 days prior to the first dose of study drugs. No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to first dose of study drugs
5. Receipt of any cytotoxic chemotherapy within 14 days prior to the first dose of study drugs
6. Receipt of any investigational medication within 30 days, or at least 5 half-lives, whichever is greater, prior to the first dose of study drugs
7. QTcF interval >480 msec at Screening. For patients with ventricular pacemakers, QTcF >500 msec
8. Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure (Class III or IV as defined by the New York Heart Association [NYHA] functional classification system)
9. Known history of stroke or cerebrovascular accident within 6 months prior to first dose of study drugs
10. Known serious active infection (e.g., human immunodeficiency virus [HIV], hepatitis B or C, tuberculosis). Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
11. Known hypersensitivity to carboplatin or other platinum-containing compounds, or mannitol
12. Pregnant or lactating women
13. Prior hematopoietic stem cell or bone marrow transplantation
14. Other uncontrolled serious chronic disease or psychiatric condition that in the Investigator’s opinion could affect patient safety, compliance, or follow-up in the protocol
15. Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to first dose of study drugs, or anticipation of the need for major surgical procedure during the course of the study
16. Receipt of a live, attenuated vaccine within 30 days prior to the first dose of study drugs or anticipation that such a live, attenuated vaccine will be required during the study treatment period

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified