Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1 (SIGNATURE)

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module - 7 Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1

The purpose of this signal seeking study was to determine whether treatment with ceritinib demonstrated sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.

This was an open label study to determine the efficacy and safety of treatment with ceritinib in patients with a diagnosis of solid tumors or hematological malignancies that had been pre-identified (prior to study consent) to have ALK or ROS1 positive mutations, translocations, rearrangements or amplifications and whose disease had progressed on or after standard treatment. The study consisted of a treatment phase where all patients received ceritinib capsules for a total dose of 750 mg daily for up to 8 cycles of 28 days. Disease assessments for clinical benefit were performed every 8 weeks until disease progression or end of treatment. Following discontinuation of treatment for any reason, patients were followed for safety for 30 days. Survival information was collected every 3 months until 2 years after the last patient had enrolled into the study. Study was amended to allow for discontinuation of survival period if primary endpoint was not met.

Study was terminated due to low enrollment.

Inclusion Criteria:

• Patient had a confirmed diagnosis of a select solid tumor (except ALK+ NSCLC) or hematological malignancy and was in need of treatment because of radiologic progression or relapse.
• Patient must have been pre-identified as having a tumor with an ALK or ROS1 positive mutation, translocation, rearrangement or amplification. The qualifying alteration must have been assessed and reported by a CLIA-certified laboratory. ALK positivity as assessed by IHC or FISH were allowed.
• Patient must have received at least one prior treatment for recurrent, metastatic and/or locally advanced disease and for whom no standard therapy options were anticipated to result in a durable remission.
• Patient had progressive and measurable disease as per RECIST 1.1 or other appropriate hematological guidelines.
• Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

Exclusion Criteria:

• Patient had received prior treatment with ceritinib.
• Patients with symptomatic CNS metastases who were neurologically unstable or required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
• Patient had received chemotherapy or anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, monoclonal antibodies or mitomycin-C) prior to starting study drug.