Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib

Key Inclusion Criteria

Patients eligible for inclusion in this study had to meet all of the following criteria:

• Patient's age was ≥ 18 years of age at the time of signing informed consent.
• Patient had a confirmed diagnosis of a selected solid tumor (except for primary diagnosis of urothelial tumors, hepatocellular carcinoma (HCC), endometrial carcinoma, metastatic breast cancer (mBC), squamous NSCLC, and renal cell carcinoma (RCC)) or hematologic malignancies (except for primary diagnosis of FLT3 AML and multiple myeloma). Additional tumor types could be excluded during the course of the study in the case of early futility or success based upon an interim analysis or at the discretion of Novartis.
• Patient was in need of treatment because of progression or relapse defined as:
• radiological progression for solid tumor and lymphoma
• for hematologic malignancies, measureable progression or relapse by appropriate criteria
• Patients had pre-identified tumor with a mutation and/or translocation of one of the known kinase targets of dovitinib. The qualifying alteration were assessed and reported by a CLIA-certified laboratory. The mutations included:
• FGFR 1-3 (amplifications were also allowed)
• PDGFRα or PDGFRβ
• VEGFR1-2 (KDR)
• FLT3, cKIT (amplifications are also allowed),
• RET, TrkA (NTRK1), or CSF-1R
• Patient had archival tissue available for submission to allow for molecular testing related to pathway activation. If the tissue was not available or not of sufficient quantity the patient was willing to undergo a fresh tumor biopsy to allow for this analysis. The sample was submitted prior to first study dose unless agreed upon between Novartis and the investigator.
• Patient 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.
• Diffuse large B cell lymphoma only: Patient received or was ineligible for autologous or allogeneic stem cell transplant. This did not apply to patients with Mantle cell lymphoma or follicular lymphoma
• Patients with measurable disease as per appropriate guidelines:

a. Solid Tumors: by RECIST 1.1

• Lymphoma: Patient had at least one measurable nodal lesion (≥2 cm) according to Cheson criteria (Cheson 2007). In case where the patient had no measurable nodal lesions ≥ 2 cm in the long axis at screening, then the patient had at least one measurable extra-nodal lesion.
• Leukemia only: Relapsed/refractory leukemia for which no standard therapy options were anticipated to result in a durable remission:
• Acute myelogenous leukemia (AML) by World Health Organization (WHO) classification (except FLT3) or acute lymphoblastic leukemia (ALL) relapsed or refractory to standard chemotherapy; unsuitable for standard chemotherapy or unwilling to undergo standard chemotherapy. Philadelphia chromosome (Ph) positive ALL eligible if failed prior tyrosine-kinase inhibitor therapy.
• Age > 60 years with AML (except FLT3) not candidates for or have refused standard chemotherapy, excluding patients with acute promyelocytic leukemia (APL) or with favorable cytogenetic abnormalities.
• For patients with Chronic Myeloid Leukemia (CML) only accelerated and blast phase CML were allowed.
• Patient with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Patient with a life expectancy of at least 16 weeks
• All Patients were having adequate bone marrow as described below:
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L (not applicable for leukemia patients).
• Platelets (PLT) ≥ 75 x 109/L (no platelet transfusion within past 14 days) (not applicable for leukemia patients).
• Hemoglobin (Hgb) ≥ 9 g/dl (not applicable for leukemia patients).
• International Normalized Ratio (INR) ≤ 1.5.
• Serum amylase and lipase ≤ upper limit of normal (ULN).
• All patients had adequate organ function defined as described below:
• Potassium, calc