S 81694 Plus Paclitaxel in Metastatic Breast Cancer

The purpose of this study is to determine the safety profile, the maximum tolerated dose (MTD) and the associated dose-limiting toxicities (DLTs) of S 81694 in combination with paclitaxel in metastatic breast cancer (mBC) patients, and to investigate the antitumour activity of the combination in metastatic triple negative breast cancer (mTNBC) patients.


Eligibility Criteria:
Inclusion Criteria:

For Phase I :

* Histologically or cytologically confirmed metastatic breast cancer, refractory to any standard therapy or for which the standard therapy is considered unsuitable;
* Patient must have at least one evaluable or measurable metastatic lesion (lesions as defined by revised Response Evaluation Criteria in Solid Tumors).

For Phase II :

* Histologically or cytologically confirmed advanced inoperable triple negative breast cancer with no prior anticancer therapy regimen in metastatic setting;
* Patient with a minimum washout period of 12 months following previous taxane based adjuvant therapy;
* Patient must have at least one measurable metastatic lesion. Ascites, pleural effusion, and bone metastases are not considered measurable;
* Acceptance of pre-treatment metastatic biopsies for all patients and on-treatment metastatic biopsies in selected centres.

For the whole study:

* Male or female subjects aged ≥ 18 years old, or legal age of the majority in the country;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
* Estimated life expectancy of at least 3 months;
* Adequate haematological function based on the last assessment performed within 7 days prior to the first IMP (investigational medicinal product) administration;
* Adequate renal function based on the last assessment performed within 7 days prior to the first IMP administration;
* Adequate hepatic function based on the last assessment performed within 7 days prior to the first IMP administration;
* Female participant of childbearing potential must have a negative pregnancy test (serum) within 7 days prior to the first day of test drug administration. Effective contraception both for female patients of childbearing potential and male patients with parteners of childbearing potential.

Exclusion Criteria:

* Other active malignancy within the last 3 years (except for basal cell carcinoma or a non-invasive/in situ cervical cancer or intra-mucosal gastro-intestinal cancers that were treated curatively);
* Presence of grade ≥ 2 toxic effects (excluding alopecia) due to prior cancer therapy;
* Known hypersensitivity to the IMP (S 81694 and paclitaxel) or their excipients;
* Evidence of peripheral neuropathy of grade 2 or higher;
* Participant previously received paclitaxel and discontinued due to toxicity related to paclitaxel;
* Participant known as refractory to taxanes;
* Any prior cancer therapy within 4 weeks or 5 half-life (whichever is the shorter) before the first IMP administration;
* Participant with current, serious, uncontrolled infections;
* Participant with brain metastasis or leptomeningeal metastasis (except patients with brain metastasis that have been stable post-radiation therapy and who are off steroids for \> 2 months);
* History of cardiac disease;
* Uncontrolled arterial hypertension;
* Presence of risk factors for torsades de pointes (e.g. heart failure, hypokalaemia, family history of long QT syndrome);
* Any clinically significant medical condition (e.g. organ dysfunction) or laboratory abnormality likely to jeopardize the patient's safety or to interfere with the conduct of the study, in the investigator's opinion.