A Study of LCL161 in Combination With Weekly Paclitaxel in Adult Patients With Advanced Solid Tumors

• Safety and tolerability of the combination, including acute and chronic toxicities [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
• Pharmacokinetics of both LCL161 and paclitaxel when administered in combination (AUC0-∞, Cmax, tmax and other parameters as appropriate) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
• Preliminary anti-tumor activity associated with this combination treatment [ Time Frame: 24 months ] [ Designated as safety issue: No ]
• Target inhibition, cell death, and cytokines in surrogate and tumor tissues [ Time Frame: 24 months ] [ Designated as safety issue: No ]

• To assess the safety and tolerability of the combination, including acute and chronic toxicities [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
• To characterize the pharmacokinetics of both LCL161 and paclitaxel24 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
• To compare the pharmacokinetics of paclitaxel with and without LCL161 in the PK expansion group during the dose expansion phase [ Time Frame: 24 months ] [ Designated as safety issue: No ]
• To describe any preliminary anti-tumor activity associated with this combination treatment [ Time Frame: 24 months ] [ Designated as safety issue: No ]
• To assess target inhibition, cell death, and cytokines in surrogate and tumor tissues [ Time Frame: 24 months ] [ Designated as safety issue: No ]

This is a dose escalation study that will assess the safety and efficacy of LCL161 in combination with weekly paclitaxel in adult patients with advanced solid tumors.

• Drug: LCL161
• Drug: Paclitaxel

Inclusion Criteria:

Patients with breast cancer must have a histologically or cytologically confirmed diagnosis of disease that has metastasized or is resistant to therapy.

Patients with ovarian cancer must have histological evidence of recurrent epithelial ovarian, fallopian tube or peritoneal cancer.

Tumor must be positive for the gene expression signature Patients must have recovered or stabilized from all toxicities related to their previous treatment except for alopecia Male or female patients 18 years or older ECOG performance status 0-1 Life expectancy greater than 12 weeks Measurable disease as determined by RECIST v1.0 Patients must give written informed consent and comply with the protocol

Exclusion Criteria:

For patients with breast cancer:

Concurrent Her2-directed or anti-estrogen therapy

For patients with ovarian cancer:

Primary refractory disease, defined as progression during initial treatment with a platinum- and taxane-containing regimen.

Prior treatment with weekly paclitaxel. More than two chemotherapy regimens given in the relapse setting. Evidence of a documented bowel obstruction within six months of study entry Patients with unresolved peripheral neuropathy, nausea, vomiting, or diarrhea ≥ CTCAE Grade 2 Any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while in the study or that could confound discrimination between disease- and study treatment-related toxicities.

Patients with impairment of GI function or GI disease that may significantly alter the absorption of LCL161 Patients who have undergone major surgery ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of procedure.

Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive β-HCG laboratory test (> 5 mIU/mL).

Known diagnosis of human immunodeficiency virus (HIV) infection or chronic active hepatitis B or C (HIV and hepatitis testing are not mandatory).

Other protocol-defined inclusion/exclusion criteria may apply