B-PRECISE-01 Study: A phase Ib trial of MEN1611, a PI3K Inhibitor, combined with trastuzumab ± fulvestrant for the treatment of HER2-positive advanced or metastatic breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS1101-TPS1101 ◽  
Author(s):  
Martine J. Piccart-Gebhart ◽  
Philippe Georges Aftimos ◽  
Francois P. Duhoux ◽  
Hans Wildiers ◽  
Nicolas Isambert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Dose Escalation ◽  
Metastatic Breast ◽  
Primary Study ◽  
Her2 Positive ◽  
Study Objective ◽  
Dose Cohort ◽  
Phase Ib ◽  
Pik3ca Mutations

TPS1101 Background: MEN1611 is a potent, selective class I inhibitor of PI3K, a key enzyme in the transduction of various extracellular growth factor signals essential for cell survival and apoptosis. The discovery in human cancers of frequent PIK3CA mutations, that have been linked to a worse outcome in advanced HER2-positive breast cancer, makes PI3K an attractive therapeutic target. Preclinical and clinical evidences support the development of MEN1611 in combination with other agents in the context of solid tumors. Methods: B-PRECISE-01 is an open-label, multicenter, phase Ib dose escalation study in patients with PIK3CA mutant tumors, HER2-positive advanced or metastatic breast cancer which has progressed after at least 2 lines of anti-HER2 based therapy. PIK3CA mutations are assessed centrally by real-time PCR assay in DNA derived from archived tumor samples. MEN1611 will be administered orally BID for continuous 28-day cycles until disease progression, in combination with weekly IV infusions of trastuzumab. In addition, HR-positive postmenopausal patients will also be treated with fulvestrant. After the completion of the dose escalation phase (Step 1), the study will continue in an expansion cohort (Step 2) testing the Recommended Phase 2 dose (RP2D) in a total of 15 patients in each of the treatment groups. The primary study objective is to assess combination safety and select RP2D. Secondary objectives include assessment of pharmacokinetics and pharmacodynamics, preliminary clinical activity of MEN1611 in combination with trastuzumab +/- fulvestrant, and correlation with PIK3CA mutations and other relevant cancer genes mutational status. Adverse events will be graded according to NCI CTCAE v4.03. Responses will be evaluated according to RECIST v1.1. Study variables will be presented by dose-cohort and overall using appropriate descriptive statistics. The enrollment began in July 2018 at European sites and US sites will shortly participate; up to date the first dose cohort level has been achieved. Clinical trial information: NCT03767335.

scholarly journals A Phase Ib Dose-Escalation and Expansion Study of the BCL2 Inhibitor Venetoclax Combined with Tamoxifen in ER and BCL2–Positive Metastatic Breast Cancer

2018 ◽  
Vol 9 (3) ◽  
pp. 354-369 ◽  
Author(s):  
Sheau W. Lok ◽  
James R. Whittle ◽  
François Vaillant ◽  
Charis E. Teh ◽  
Louisa L. Lo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Dose Escalation ◽  
Metastatic Breast ◽  
Phase Ib

Trastuzumab emtansine plus pertuzumab in Japanese patients with HER2-positive metastatic breast cancer: a phase Ib study

Breast Cancer ◽  
2018 ◽  
Vol 26 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Emi Noguchi ◽  
Kenji Tamura ◽  
Masaya Hattori ◽  
Jun Horiguchi ◽  
Nobuaki Sato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Japanese Patients ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Phase Ib

scholarly journals Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3509
Author(s):  
Elena López-Miranda ◽  
José Manuel Pérez-García ◽  
Serena Di Cosimo ◽  
Etienne Brain ◽  
Maja Ravnik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Liposomal Doxorubicin ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Maximum Tolerated Dose ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Open Label ◽  
Phase Ib

The paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled anthracycline-naïve HER2+ MBC patients who had progressed on trastuzumab and taxanes. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m2) in the “3 plus 3” dose-escalation part. During expansion, they received 60 mg/m2 of NPLD every 3 weeks (Q3W) plus standard doses of T-DM1. The MTD was T-DM1 3.6 mg/kg plus NPLD 60 mg/m2 administered IV Q3W. No clinically relevant worsening of cardiac function was observed. Among all evaluable patients, the overall response rate was 40.0% (95%CI, 16.3–67.7) with a median duration of response of 6.9 months (95%CI, 4.8–9.1). Clinical benefit rate was 66.7% (95%CI, 38.4–88.2) and median progression-free survival was 7.2 months (95%CI, 4.5–9.6). No significant influence of NPLD on T-DM1 pharmacokinetics was observed. The addition of NPLD to T-DM1 is feasible but does not seem to improve the antitumor efficacy of T-DM1 in HER2+ MBC patients.

Gemcitabine plus paclitaxel and gemcitabine plus docetaxel in first- or second-line metastatic breast cancer: A phase II randomized trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1046-1046 ◽  
Author(s):  
R. V. Boccia ◽  
L. Vaughn ◽  
H. Zeigler ◽  
Y. Wang ◽  
J. Gill ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Primary Study ◽  
Similar Response ◽  
Study Objective ◽  
Study Results ◽  
Combination Regimens

1046 Background: The combination of gemcitabine (G) with paclitaxel (P) has proven efficacy in the first-line treatment of metastatic breast cancer (MBC). In addition, the combination of G with docetaxel (D) has shown activity in several nonrandomized, Phase II, MBC trials. This randomized Phase II trial was conducted to assess the efficacy and safety of G plus P and G plus D combination regimens in previously treated patients with MBC. Methods: Patients with locally advanced or metastatic breast cancer were randomized equally into two groups to receive either GP (G 1,250 mg/m2 IV on Days 1 and 8 plus P 175 mg/m2 IV on Day 1) or GD (G 1,000 mg/m2 IV on Days 1 and 8 plus D 75 mg/m2 IV on Day 1). Treatment was administered every 21 days and continued until disease progression or undue toxicity. Planned enrollment was 112 patients (56 per group). The primary study objective was tumor response assessed using RECIST criteria. Toxicities were assessed using the NCI Common Toxicity Criteria, Version 2.0. Results: Twenty-five patients were enrolled in each treatment group and accrual was stopped due to slow enrollment. In the GP group, only 23 patients were evaluable for response and 24 patients were monitored for safety. One patient did not receive study medication and was not assessed for efficacy or safety. A second patient was determined to have nonmeasurable disease at baseline and was not assessed for response. Overall response rate was 39% (95% CI 20, 61) for the GP group and 40% (95% CI 21, 61) for the GD group. The median number of cycles administered was 6.5 in the GP group and 6.0 in the GD group. Detailed study results are summarized in the table below. Conclusions: These results show that GP and GD combination regimens are both efficacious in the treatment of MBC, with similar response rates and manageable toxicity profiles. [Table: see text] No significant financial relationships to disclose.

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