Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Dovitinib · 8 trials · 11 indications
Assessed according to RECIST 1.1. PFS was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause. If a patient had not progressed or died, on the date of the analysis cut-off or when he/she received any further anti-neoplastic therapy, PFS was censored on the date of last tumor assessment before the cutoff date or the anti-neoplastic therapy date. The distribution of PFS was estimated using the Kaplan-Meier method. The median PFS along with 95% confidence intervals was presented by treatment group.
The primary outcome measure is the clinical benefit rate, defined as an objective response (complete \[CR\] or partial \[PR\]) or stable disease \[SD\] of ≥6 months duration according to the RECIST version 1.1 criteria.
Participants with grades 3 and 4 severity adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03, unless otherwise specified. AEs are provided by System Organ Class (SOC). A patient with multiple adverse events within a primary system organ class was counted only once in the total row.
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
DCR is defined as the proportion of patients with a best overall response of Complete Responses (CR), Partial Response (PR) and Stable Disease (SD) at 12 weeks according to RECIST (version 1.1). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
The overall survival (OS), defined as the time from date of randomization to the date of death from any cause. If a patient was not known to have died at the date of analysis cut-off, OS was censored at the last date of contact. Survival information was collected every 6 wks until at least 130 deaths have been observed
Cmax will be evaluated after a single dose of TKI258 and at the steady state following a 5 days on/2 days off dosing schedule. Cmax is the maximum (peak) plasma, blood, serum, or other body fluid drug concentration after a single dose administration (mass x volume - 1).
Tmax will be evaluated after a single dose of TKI258 and at the steady state following a 5 days on/2 days off dosing schedule. Tmax is the time to to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after a single dose administration (mass x volume - 1).
AUClast will be evaluated after a single dose of TKI258 and at the steady state following a 5 days on/2 days off dosing schedule. AUC from time zero to the last measurable concentration sampling time t(last) (mass x time x volume\^-1)
AUCinf is the time to zero to infinity (mass x time x volume)
| Arm | Type | Description |
|---|---|---|
| Dovitinib + best supportive care (BSC) | EXPERIMENTAL | Patients randomized to the dovitinib treatment arm received 500 mg of dovitinib orally on 5 days on/2 days off dosing schedule. |
| Sorafenib + BSC | ACTIVE_COMPARATOR | Patients in the sorafenib control arm received400 mg of sorafenib (2 x 200 mg tablets) orally taken twice daily. |
| Dovitinib | EXPERIMENTAL | Dovitinib 500 mg PO OD (5 days on, 2 days off); Each cycle = 28 days |
| dovitinib + fulvestrant | EXPERIMENTAL | Participants were given dovitinib and fulvestrant coadministration starting with last assigned dose and regimen which patient received in parent study. Additional dose modifications were at the discretion of the investigator based on guidance provided in the protocol and IB. |
| TKI258 | EXPERIMENTAL | Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule. |
| Dovitinib (TKI258) | EXPERIMENTAL | Patients will receive Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal. |
| Sorafenib | EXPERIMENTAL | tablet |
| TKI258 normal hepatic function | EXPERIMENTAL | TKI258 Capsule, @ 500 mg p.o. o.d. 5 days on/2 days off |
| TKI258 mild hepatic impairment | EXPERIMENTAL | TKI258 capsule @ 500 or 400 mg p.o. o.d. 5 days on/2 days off |
| TKI258 moderate hepatic impairment | EXPERIMENTAL | TKI258 capsule @ starting dose at 400 mg p.o. o.d. 5 days on/2 days off |
| TKI258 severe hepatic impairment | EXPERIMENTAL | TKI258 capsule Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups |
| Name | Type | Description |
|---|---|---|
| Dovitinib | DRUG | Dovitinib is formulated as an oral gelatin capsule of 100 mg strength and was dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule. Medication labels complied withthe legal requirements of each country and were printed in the local language. |
| Sorafenib | DRUG | Sorafenib is formulated as a round, oral, biconvex, red film-coated tablet that contains 200 mg of sorafenib (tosylate). Sorafenib was administered twice daily without food at least 1 hour before or 2 hours after a meal. Sorafenib was supplied according to local practice. |
| fulvestrant | DRUG | Fulvestrant is generally available as solution for injection in pre-filled syringes containing 250 mg of fulvestrant in 5 mL solution. |
| Dovitinib (TKI258) | DRUG | Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule. |
| fluvoxamine | DRUG | perpetrator drug; 7 days of dosing |
Inclusion Criteria: * Patients with metastatic renal cell carcinoma (mRCC) with histological or cytological confirmation of clear cell carcinoma or a component of clear cell * Patients must have received one and only one prior VEGF-targeted therapy and one and only one prior mTOR inhibitor therapy ...
Dovitinib is an investigational small molecule being studied in oncology for several tumor types, including gastrointestinal stromal tumors, recurrent adenoid cystic carcinoma of the salivary glands, metastatic renal cell carcinoma, advanced solid tumors excluding breast cancer, and hepatocellular carcinoma. It is not approved and remains in clinical development.
Dovitinib is being developed by Novartis AG, traded on the New York Stock Exchange under the ticker NVS. The company has sponsored multiple clinical trials of the drug across various solid tumor indications.
Dovitinib is in Phase 2 clinical development. It has completed trials including a Phase 3 study in metastatic renal cell carcinoma, but it remains investigational and is not FDA approved. The drug is still being evaluated for safety and efficacy.
Dovitinib has completed several trials, including NCT01223027, a Phase 3 study comparing it to sorafenib in metastatic renal cell carcinoma with 564 participants, and NCT01443481, a Phase 1 pharmacokinetics study in cancer patients with hepatic impairment. Other completed trials include NCT01678105 in adenoid cystic carcinoma and NCT02116803, a long-term safety extension study.
Yes, Dovitinib is also known as TKI258. Clinical trial titles refer to it as TKI258, such as in the pharmacokinetics study NCT01443481, which evaluates TKI258 in cancer patients with normal and impaired hepatic function.