Abstract P6-20-07: Efficacy and safety of CB-839, a small molecule inhibitor of glutaminase, in combination with paclitaxel in patients with advanced triple negative breast cancer (TNBC): Initial findings from a multicenter, open-label phase 2 study

2019 ◽  
Author(s):  
G Vidal ◽  
K Kalinsky ◽  
E Stringer-Reasor ◽  
F Lynce ◽  
J Cole ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Small Molecule ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Open Label ◽  
Molecule Inhibitor ◽  
Phase 2 Study ◽  
Open Label Phase

scholarly journals Dasatinib as a Single Agent in Triple-Negative Breast Cancer: Results of an Open-Label Phase 2 Study

2011 ◽  
Vol 17 (21) ◽  
pp. 6905-6913 ◽  
Author(s):  
Richard S. Finn ◽  
Carmelo Bengala ◽  
Nuhad Ibrahim ◽  
Henri Roché ◽  
Joseph Sparano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Single Agent ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Study ◽  
Open Label Phase

scholarly journals 339 Immune profiling to investigate improved survival in patients with metastatic triple-negative breast cancer receiving trilaciclib prior to chemotherapy

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A365-A365
Author(s):  
Aaron Stevens ◽  
Joyce O’Shaughnessy ◽  
Subing Cao ◽  
Jessica Sorrentino ◽  
Janet Horton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Triple Negative Breast Cancer ◽  
Cd8 T Cells ◽  
Triple Negative ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase ◽  
Tumor Inflammation

BackgroundTrilaciclib is an intravenous cyclin-dependent kinase 4/6 inhibitor approved to reduce the incidence of chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer (myeloprotection). In a randomized, open-label phase 2 trial in patients with metastatic triple-negative breast cancer (mTNBC), adding trilaciclib prior to gemcitabine/carboplatin (GCb) increased overall survival in both PD-L1–positive and –negative populations versus GCb alone.1 2 We investigated potential immune mechanisms of anti-tumor efficacy among patients who received trilaciclib plus GCb.MethodsPeripheral blood was collected prior to and on treatment for flow cytometric analysis, and total RNA isolated from diagnostic tumor biopsies for sequencing. Differential gene expression analysis between responders and non-responders was based on negative binomial distribution and related pathways identified by Kyoto Encyclopedia of Genes and Genomes pathway analysis. Tumor inflammation signatures and deconvolution-based approaches were used to assess the tumor immune microenvironment. PD-L1 expression was considered positive if ≥1% of the total tumor area contained PD-L1–labelled immune cells (Ventana SP142 assay). Patients were defined as responders (confirmed complete or partial response) or non-responders (stable or progressive disease) according to RECIST criteria.ResultsOf 68 patients who received trilaciclib prior to GCb, tumor response status and RNA sequencing data were available for 51 patients, comprising 24 responders and 27 non-responders. Tumors from responders had 253 differentially expressed genes compared with non-responders. Analysis of immune gene signatures revealed a higher T-cell exhaustion score at baseline among responders versus non-responders (P=0.044).Among patients with PD-L1–positive tumors, responders had a greater peripheral immune response at baseline compared with non-responders, including more T cells (P=0.037; particularly memory CD8 T cells [P=0.042]), and a trend toward fewer myeloid-derived suppressor cells (MDSCs). Additionally, tumors from responders had more dendritic cells (P=0.044) and a trend toward enriched tumor inflammation signatures compared with non-responders.By contrast, among patients with PD-L1–negative tumors, responders had similar peripheral immune populations at baseline compared with PD-L1–negative non-responders, but fewer MDSCs (P=0.016), and a trend toward increased T-cell numbers after two cycles of trilaciclib plus GCb.Responders with both PD-L1–positive and –negative tumors had increased numbers of naïve CD8 T cells after two treatment cycles compared with non-responders.ConclusionsThe data suggest that adding trilaciclib prior to GCb enhances antitumor efficacy by modulating the composition of immune cell subsets. The impact of trilaciclib on changes to the tumor-infiltrating immune response is being further investigated in a phase 3 trial in patients with mTNBC (NCT04799249).AcknowledgementsFlow cytometry and RNA sequencing analyses were performed by Covance, Inc., and Q2 Laboratory Solutions, respectively.Trial Registration www.clinicaltrials.govNCT02978716ReferencesTan AR, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, Vojnović Ž, Vasev N, Ma L, Richards DA, Wilks ST, Milenković D, Yang Z, Antal JM, Morris SR, O’Shaughnessy J. Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol 2019;20(11):1587–1601.O’Shaughnessy J, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, Vojnović Ž, Vasev N, Ma L, Richards DA, Wilks ST, Milenković D, Xiao J, Sorrentino JA, Horton J, Tan AR. Abstract PD1-06: trilaciclib improves overall survival when given with gemcitabine/carboplatin in patients with metastatic triple-negative breast cancer: final analysis of a randomized phase 2 trial. Cancer Res 2021;81(4 Supplement):PD1-06.Ethics ApprovalThe study protocol and all associated amendments and study-related materials were approved by the institutional review board or independent ethics committee of each investigational site.

Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial

2021 ◽  
Vol 22 (4) ◽  
pp. 499-511 ◽  
Author(s):  
Eric P Winer ◽  
Oleg Lipatov ◽  
Seock-Ah Im ◽  
Anthony Goncalves ◽  
Eva Muñoz-Couselo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Open Label ◽  
Phase 3 ◽  
Open Label Phase

scholarly journals Glembatumumab vedotin for patients with metastatic, gpNMB overexpressing, triple-negative breast cancer (“METRIC”): a randomized multicenter study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Linda T. Vahdat ◽  
Peter Schmid ◽  
Andres Forero-Torres ◽  
Kimberly Blackwell ◽  
Melinda L. Telli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Primary Endpoint ◽  
Triple Negative ◽  
Progression Free Survival ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Common Grade ◽  
Open Label Phase ◽  
Grade 3

AbstractThe METRIC study (NCT#0199733) explored a novel antibody–drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.88 mg/kg IV q21 days) or capecitabine (2500 mg/m2 PO daily d1–14 q21 days). The primary endpoint was RECIST 1.1 PFS per independent, blinded central review. In all, 327 patients were randomized to GV (213 treated) or capecitabine (92 treated). Median PFS was 2.9 months for GV vs. 2.8 months for capecitabine. The most common grade ≥3 toxicities for GV were neutropenia, rash, and leukopenia, and for capecitabine were fatigue, diarrhea, and palmar-plantar erythrodysesthesia. The study did not meet the primary endpoint of improved PFS over capecitabine or demonstrate a relative risk/benefit improvement over capecitabine.

Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2 -amplified early stage breast cancer: a single-group, open-label, phase 2 study

2013 ◽  
Vol 14 (11) ◽  
pp. 1121-1128 ◽  
Author(s):  
Stephen E Jones ◽  
Rufus Collea ◽  
Devchand Paul ◽  
Scot Sedlacek ◽  
Anne M Favret ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Phase 2 ◽  
Single Group ◽  
Open Label ◽  
Phase 2 Study ◽  
Open Label Phase
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