PQR309 and Eribulin in Metastatic HER2 Negative and Triple-negative Breast Cancer (PIQHASSO)
PQR309 and Eribulin in Metastatic HER2 Negative and Triple-negative Breast Cancer (PIQHASSO)
This study is an open-label,non randomized, multi-center, phase 1/2b (dose escalation
 followed by expansion part) study evaluating clinical safety, efficacy and pharmacokinetics
 of PQR309 in combination with standard dose of eribulin in patients with locally advanced or
 metastatic HER2-negative (escalation part) and Triple Negative Breast Cancer (expansion
 part).
-  The primary objective of the escalation part is to assess the maximum tolerated dose
 (MTD) of PQR309 combined with the standard eribulin dose in patients with HER2 negative
 breast cancer following a "modified" 3 by 3 design.

 -  For the expansion part the objective is to evaluate efficacy of PQR309 in combination
 with eribulin in patients with Triple Negative Breast Cancer

 -  Once the MTD of continuous daily PQR309 dosing has been established, intermittent
 schedules of PQR309 ("2 days on/ 5 days off" or "Monday / Thursday") will be evaluated.
Inclusion Criteria:

 -  Histologically/cytologically confirmed diagnosis of breast cancer. Radiological
 evidence of inoperable locally advanced or metastatic breast cancer.

 -  HER2 negative breast cancer (based on the most recent analyzed biopsy) defined as a
 negative in situ hybridization test or an immunohistochemistry status of 0, 1+ or 2+.

 -  Received at least 2 and no more than 5 prio chemotherapeutic regimens in locally
 advanced and/or metastatic setting.

 -  Prior therapy has to include an anthracycline and a taxane in any combination or
 order.

 -  For Expansion part:

 Triple-negative breast cancer defined as a negative in situ hybridization test or an
 immunohistochemistry (IHC) status of 0,1+ or 2+ER abnd PR status <10% by local laboratory
 testing.

 Exclusion Criteria:

 -  Previous systemic treatment with PI3K,mTOR or AKT inhibitors (allowed in the
 escalation part).

 -  Previous treatment with eribulin (allowed in the escalation part). Known
 hypersensitivity to any of the excipients of PQR309 or eribulin.Concurrent treatment
 with other approved or investigational antineoplastic agent.

 -  Symptomatic Central Nervous System metastases. The patient must have completed any
 prior local treatment for CNS metastases > 28 days prior to first dose of the study
 drug (including radiotherapy and/or surgery).

 -  Clinically manifested diabetes mellitus(treated and/or clinical signs with fasting
 glucose >125mg/dl or HbA1c>7%), or documented steroid induced diabetes mellitus.