Safety and Efficacy of AEB071 in Metastatic Uveal Melanoma Patients

• Frequency of dose limiting toxicity during cycle 1 (28 days) - Dose Escalation [ Time Frame: cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
• Number of participants reporting serious adverse events and adverse events - Dose Expansion [ Time Frame: Baseline, every 28 days ] [ Designated as safety issue: Yes ]

• Overall response rate (Complete Response (CR) + Partial Response(PR)) to AEB071 using RECIST version 1.1 [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
• Progression free survival and time to progression using RECIST version 1.1 [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
• Number of patients reporting serious adverse events and adverse events [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: Yes ]
• AEB071/AEE800 pharmacokinetic parameters including Cmax, tmax, AUCτ, Ctrough, CL/F, and RA [ Time Frame: First 7 months of treatment period ] [ Designated as safety issue: No ]
• Gα genotype in tumor specimens [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]

This study has two parts, dose escalation and dose expansion. For dose escalation, the primary objective is to estimate the maximum tolerated dose (MTD) of AEB071 in patients with uveal melanoma. For dose expansion, the primary objective is to characterize the safety and tolerability of the MTD of AEB071 in patients with uveal melanoma.

Inclusion Criteria:

• Uveal melanoma with biopsy proven metastatic disease
• Males and females ≥ 18 years of age
• Consent to biopsy of tumor
• Evaluable disease (escalation part only) or measurable disease according to RECIST v1.1
• WHO performance status of ≤ 1

Exclusion Criteria:

• Patients with abnormal laboratory values as defined by the protocol
• Patients who are receiving treatment with strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued prior to study entry
• Patients with impaired cardiac function or clinically significant cardiac diseases as defined by the protocol
• Patients with another malignancy that was treated within the last three years with the exceptions of localized basal cell carcinoma and cervical carcinoma
• Patients with impairment of gastrointestinal function or disease
• Patients with severe systemic infections
• Patients who are known to be HIV positive and/or have active hepatitis B or C infection

• Time since last therapy for treatment of underlying malignancy:

  • Cytotoxic chemotherapy: ≤ duration of the most recent cycle of the previous regimen (a minimum of 2 weeks for all)
  • Nitrosurea: ≤ 6 weeks
  • Biologic therapy: ≤ 4 weeks
  • ≤ 5 x PK half-life of a small molecule therapeutic not otherwise defined above
• Patients having undergone major surgery less than 4 weeks prior to enrollment or have not fully recovered from prior surgery
• Women of child-bearing potential unless they are using highly effective methods of contraception during the dosing and for at least 36 hours after last dose. Highly effective contraception as defined in the protocol.
• Patients with primary central nervous system tumors or brain metastases.
• Pregnant or nursing (lactating) women.

Other protocol-defined inclusion/exclusion criteria may apply