S 81694 Plus Paclitaxel in Metastatic Breast Cancer

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.