A Study to Evaluate the Potential Benefit of the Addition of BYL719 to Paclitaxel in the Treatment of Breast Cancer and Head-and-neck Cancer

This is an interventional treatment trial for Neoplasms, Breast Neoplasms, Head and Neck Neoplasms focused on measuring Solid tumors, Head and neck non squamous cell carcinoma, breast cancer, PI3K inhibitor, BYL719, paclitaxel Read More

Inclusion criteria For entire trial:

1. - Adult > or = 18 years old
2. - has signed the Informed Consent Form (ICF)
3. - has at least one measurable or non-measurable disease as per RECIST 1.1
4. - has tumor tissue available for the analysis as described in the protocol
5. - has adequate bone marrow and organ function as defined in the protocol
6. - is able to swallow and retain oral medication for the dose escalation part, ALL above PLUS
7. - has a histologically-confirmed, advanced unresectable solid tumors who have progressed on standard therapy (or not been able to tolerate) within three months before screening/baseline visit or for whom no standard anticancer therapy exists.

8. - has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 For dose expansion part, patient has ALL of above first six criteria PLUS either: 9- has a histologically/cytologically-confirmed HNSCC as detailed in the protocol and an ECOG performance status ≤ 1 or:

   • Patient is a Female with a histologically and/or cytologically confirmed diagnosis of breast cancer as detailed in the protocol and an ECOG performance status ≤ 1

Common exclusion criteria to Dose escalation and Dose expansion parts:

1. - has received previous treatment with a PI3K or AKT inhibitor as described in the protocol
2. - has a known hypersensitivity to paclitaxel or other products containing Cremophor
3. - has a contraindication to use the standard pre-treatment for paclitaxel
4. - has a primary central nervous system (CNS) tumor or CNS tumor involvement as detailed in the protocol
5. - has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
6. - has received radiotherapy > or = 4 weeks prior to starting study drugs, with exception of palliative radiotherapy, who has not recovered from side effects of such therapy to baseline or Grade ≤ 1 and/or from whom ≥ 30% of the bone marrow was irradiated
7. - has peripheral sensory neuropathy with functional impairment (CTC grade 2 neuropathy or higher)
8. - has undergone major surgery ≤ 4 weeks prior to starting study treatment or who has not recovered from side effects of such procedure
9. - has a clinically significant cardiac disease or impaired cardiac function as detailed in the protocol
10. - is currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment
11. - has diabetes mellitus requiring insulin treatment and/or with clinical signs
12. - has impaired gastrointestinal (GI) function or GI disease as described in the protocol
13. - has a known positive serology for human immunodeficiency virus (HIV), active Hepatitis B, and/or active Hepatitis C infection
14. - has any other condition that would, in the Investigator's judgment, preclude patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures
15. - is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzymes CYP3A or CYP2C8 as detailed in the protocol
16. - is currently receiving treatment with agents that are metabolized solely by CYP3A and/or have a narrow therapeutic window
17. - has a history of another malignancy within 2 years prior to starting study treatment, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix
18. - Patient has a history of non-compliance to medical regimen or inability to grant consent
19. - Pregnant or nursing (lactating) women
20. - does not apply highly effective contraception during the study and through the duration as defined in the protocol

For the HNSCC patient's cohort additional exclusion criteria are:

21- Treatment with more than one prior chemotherapy for recurrent/metastatic disease as detailed in the protocol 22- Prior taxane treatment for metastatic disease additional exclusion criteria for breast cancer patients' cohort:

- has received any prior cytotoxic therapy for the inoperable locally advanced (recurrent or progressive) or metastatic disease, or who had a progression/recurrent disease within 6 months after completion of an adjuvant/neoadjuvant therapy as described in the protocol

Other protocol-defined inclusion/exclusion criteria may apply