Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Leukemia

Hematologic Neoplasms

Melanoma

Thyroid Neoplasms

Thyroid Diseases

Gastrointestinal Stromal Tumors

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Head and Neck Neoplasms

Myeloid Leukemia

Acute Myeloid Leukemia

Ovarian Cancer

Ovarian Epithelial Cancer

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.

Dovitinib (TKI258)

Novartis Pharmaceuticals

The purpose of this signal seeking study was to determine whether treatment with dovitinib (TKI258) demonstrated sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.

This was a phase II, open label study to determine the efficacy and safety of treatment with dovitinib (TKI258) in patients with a diagnosis of select solid tumors or hematological malignancies that have been pre-identified (prior to study consent) to have mutations, translocations or amplifications and whose disease has progressed on or after standard treatment.

Genomic profiling is becoming more accessible to patients and their physicians. As such, more patients have been identified with potentially-actionable mutations, translocations or amplifications but do not have access to targeted drug treatment. This is a signal-seeking study to match patients with tumor pathway activations inhibited by dovitinib to the RTK inhibitor dovitinib. Pre-identification of mutations, translocations, or amplifications will be performed locally at a CLIA certified laboratory prior to participation on the trial.

For the purpose of this study, genomic profiling is not considered part of screening. Informed consent must be signed before any screening activities take place. Once eligibility (screening criteria met) has been confirmed by Novartis, the patient will initiate therapy with dovitinib single-agent. The patient may not receive any additional anti-cancer therapy during treatment with dovitinib.

Patients received study treatment until disease progression (assessed by investigator per RECIST 1.1 or appropriate hematologic response criteria), unacceptable toxicity, death or discontinuation from study treatment for any other reason (e.g., withdrawal of consent, start of a new anti-neoplastic therapy or at the discretion of the investigator), otherwise known as End of Treatment. All patients who discontinue from study treatment due to disease progression must have their progression clearly documented.

Disease assessment (by RECIST 1.1 or appropriate hematological response criteria) will be performed every 8 weeks (±4 days) after first dose of study drug (Day 1 of every odd cycle), until disease progression or end of treatment, whichever occurs first. The frequency of disease assessment may be reduced to every 12 weeks for patients who have at least 4 post-baseline disease assessments and are clinically stable (except AML patients). Scans was assessed locally by the investigator. After discontinuation of treatment, patients, regardless of reason for treatment discontinuation, will be followed for safety for 30 days after the last dose.

All patients will be followed for survival status every 3 months for 2 years after the last patient has enrolled in the study,regardless of treatment discontinuation reason (except if consent is withdrawn or patient is lost to follow-up)

Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 2 - Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib Including Tumors With Mutations or Translocations of FGFR, PDGFR, VEGF, cKIT, FLT3, CSFR1, Trk and RET

CBR determined by investigator assessment for each tumor assessment \& defined as responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) ≥ 16 wks. Confirmed CR/PR or SD prior to 16 wks,but discontinued prior to 16 wks for reasons other than progressive disease,will have their clinical benefit defined non-evaluable; confirmed CR/PR or SD prior to 16 wks,but progressed prior to 16 wks,will be considered not achieving clinical benefit;if CR/PR/SD occurred prior to 16 wks,but progressed at or after 16 wks without evidence of CR/PR/SD at or after 16 wks,will also be considered not achieving clinical benefit. CBR will be analyzed by comparing achieved CBR with a historical control rate of each tumor type,\& if there is at least 90% probability that the response rate in a tumor type exceeds the historical rate,then the tumor type will be considered a success. CBR: CR+PR+SD the assessment criteria was RECIST 1.1

Overall Response (OR) of Partial Response (PR) or greater based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria will apply and are included in the appendices. ORR: CR+PR

Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause.

Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact

TKI258

Age, Continuous

Sex: Female, Male

Study Director

Complete response (CR)

Partial response (PR)

Stable disease (SD)

Clinical benefit rate (CBR)

Full Analysis Set (FAS) included all patients who received at least one dose of study drug.

FAS was used for the analysis of efficacy endpoints.

Clinical Benefit Rate (CBR)

Overall response rate (ORR)

Overall Response (OR) of Partial Response (PR) or Greater

Progression-Free Survival (PFS)

Overall Survival (OS)

Overall Study

Hematologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Infigratinib

BGJ398 was dosed on a flat scale of 125 mg (e.g., 1 x 100 mg and 1 x 25 mg capsules) once daily for the first 21 days of the 28-day cycle (3 weeks on, 1 week off in a cycle). A complete treatment cycle is defined as 28 days.

BGJ398

The purpose of this signal seeking study was to determine whether treatment with BGJ398 demonstrates sufficient efficacy in select FGFR pathway-regulated solid tumors and/or hematologic malignancies to warrant further study.

BGJ398 for Patients With Tumors With FGFR Genetic Alterations

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 6 - BGJ398 for Patients With Tumors With FGFR Genetic Alterations

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Tumor Response: Overall response rate (ORR) and clinical benefit rate (CBR) for solid tumor (non-lymphoma) which excludes 3 TIO and 1 Lymphoma patients (hence 80 patients and not 84)

Clinical benefit rate for patients with solid tumors were assessed using RECIST 1.1 and include responses of CR or PR or SD. For hematologic tumors other appropriate hematological response criteria may apply

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

The key secondary endpoint, OR, was determined by Investigator assessment for each tumor assessment and defined as responses of CR and PR per RECIST version 1.1.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Kaplan-Meier estimates of PFS timing, months

Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause

Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause

Overall survival (OS) is the time from the date of start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last contact.

The duration of response (PR or greater) applies only to patients whose best response was PR or greater. It is defined as the Ttime from the first documented response to the date first documented disease progression or relapse or death due to any cause

All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 26.6 months

<65 years

>=65-<75 years

>=75 years

Age, Customized

Caucasian

Black

Asian

Other

Race/Ethnicity, Customized

Full Analysis Set (FAS): The FAS included all enrolled patients who received at least 1 dose of study drug. The FAS was the primary set for efficacy analyses.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib	NCT01831726	Tumor Pathway A...	Dovitinib (TKI2...	18 Years - 100 Years	Novartis
BGJ398 for Patients With Tumors With FGFR Genetic Alterations	NCT02160041	Solid Tumor Hematologic Mal...	BGJ398	18 Years -	Novartis

Spots Global Cancer Trial Database for translocations