Study of Safety & Efficacy of the Combination of LJM716 & BYL719 in Patients With Previously Treated Esophageal Squamous Cell Carcinoma (ESCC)

The study design included a Phase 1b dose escalation portion to define the maximum tolerated
dose (MTD)/recommended phase 2 dose (RP2D) for the combination of LJM716 and alpelisib,
followed by an open-label, randomized Phase 2 part to compare anti-tumor activity of
LJM716-alpelisib combination versus physician's choice of second-line therapy (paclitaxel,
docetaxel, irinotecan). However, the phase 2 part was not conducted as the study was
terminated early due to limited anti-tumor activity with LJM716-alpelisib combination
observed in phase 1b.

Inclusion Criteria:

- Histologically confirmed esophageal squamous cell carcinoma (ESCC)

- No more than one prior chemotherapy regimen for recurrent or metastatic ESCC (for
Phase II only).

- Progression during or after platinum-based therapy for recurrent or metastatic ESCC,
or recurrence within 6 months of platinum-based chemotherapy or chemoradiotherapy for
localized disease.

Exclusion Criteria:

- Patients who received prior phosphoinositide-3-kinase (PI3K) inhibitor or
anti-receptor tyrosine-protein kinase erbB-3 (ERBB3 or HER3) antibody treatment,
including bi-specific antibodies with HER3 as one of the targets (patients with prior
exposure to pertuzumab or epidermal growth factor receptor (EGFR)-targeted agents are
eligible)

- Patients who do not have an archival or fresh tumor sample (or sections of it)
available or readily obtainable.

- Patients with central nervous system (CNS) metastatic involvement.

- Patients who have received prior systemic anti-cancer treatment, such as cyclical
chemotherapy or biological therapy within a period of time that is shorter than the
cycle length used for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C)
prior to starting study treatment.

- Patients who have received definitive radiotherapy ≤ 4 weeks prior to starting study
drug, who have not recovered from side effects of such therapy and/or from whom ≥ 30%
of the bone marrow was irradiated.

- Other protocol-defined inclusion/exclusion criteria may apply.