Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as MGCD516
sitravatinib · 6 trials · 6 indications
An AE is any reaction, side effect or other undesirable medical event that occurs during participation in a clinical trial, regardless of treatment group or suspected causal relationship to study treatment. Assessment of AEs will include type, incidence, severity (graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE, Version 5.0\]), timing, seriousness, and relatedness to study treatment. A treatment-emergent AE (TEAE) is an AE that occurs after the first dose of any study treatment or any pre-existing condition that increases in severity after the first dose of study treatment.
Number of participants with treatment related adverse events which lead to study drug discontinuation.
An abnormal laboratory test result should be reported as an AE in the CRF only if it is associated with one or more of the following: * Clinical symptoms; * Requires additional tests (beyond repeats), treatment, or intervention; * Results in change in study treatment dosing; * Requires discontinuation from study treatment; and/or * Considered by the investigator or sponsor to be an AE.
Objective response is defined as the percent of participants documented by investigator assessment to have Complete Response (CR) or Partial Response (PR) in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions.
Number and percentage of participants who experienced a response prior to surgery in accordance with RECIST 1.1. * CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; * PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions; * Stable Disease (SD) is concluded when the single point in time response does not qualify for CR, PR or Progressive Disease (PD); * PD is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing nontarget lesions.
(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib
(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib
(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib
Characterization of AEs by incidence, severity, timing, seriousness \& relationship to study treatment
AUC from time zero to the last measured time point
Time to reach maximum observed plasma concentration
Area under the plasma concentration-time curve from time zero extrapolated to infinity moderate, or severe hepatic impairment compared to control subjects with normal hepatic function
Maximum observed plasma concentration
Terminal elimination half-life
Apparent total plasma clearance when dosed orally
Apparent volume of distribution when dosed orally
Unbound fraction
Characterization of AEs by incidence, severity, timing, seriousness \& relationship to study treatment
| Arm | Type | Description |
|---|---|---|
| Phase 2/3: Open label extension of parent study | EXPERIMENTAL | The current study is designed to allow continued access to sitravatinib and to evaluate the safety and tolerability of sitravatinib alone or in combination with other anticancer therapies in patients who are deriving clinical benefit in a previous parent clinical trial. |
| Sitravatinib and nivolumab | EXPERIMENTAL | Sitravatinib oral capsule administered daily 2 weeks alone then in combination with nivolumab administered as 240 mg IV every 2 weeks. Total treatment duration: 6-8 weeks prior to planned nephrectomy. |
| Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort) | EXPERIMENTAL | To evaluate the potential for drug-drug interactions (DDI) with sitravatinib monotherapy. To determine the effect of sitravatinib on the pharmacokinetics (PK) of midazolam (CYP3A4 probe substrate), warfarin (CYP2C9 probe substrate), dextromethorphan (CYP2D6 probe substrate), rosuvastatin (BCRP probe substrate), and digoxin (P-gp probe substrate). |
| Phase 1, Part 1: Sitravatinib monotherapy (QTc cohort) | EXPERIMENTAL | To evaluate the QTc prolongation risk for sitravatinib in patients with advanced/metastatic solid tumors via C-QTc modeling. |
| Phase 1, Part 2: Combination Therapy (both DDI and QTc cohorts) | EXPERIMENTAL | To evaluate safety and tolerability of Sitravatinib treatment with the addition of the checkpoint inhibitor nivolumab. |
| Sitravatinib in healthy subjects | EXPERIMENTAL | Participants will receive a single dose of sitravatinib 100 mg receive on Day 1 in healthy subjects. |
| Sitravatinib in subjects with mild hepatic impairment | EXPERIMENTAL | Participants will receive a single dose of sitravatinib 100 mg receive on Day 1 in subjects with mild hepatic impairment |
| Sitravatinib in subjects with moderate hepatic impairment | EXPERIMENTAL | Participants will receive a single dose of sitravatinib 100 mg receive on Day 1 in subjects with moderate hepatic impairment |
| Sitravatinib in subjects with severe hepatic impairment | EXPERIMENTAL | Participants will receive a single dose of sitravatinib 100 mg receive on Day 1 in subjects with severe hepatic impairment |
| Phase 1: Dose Escalation | EXPERIMENTAL | Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment. |
| Phase 1b Dose Escalation Cohort A | EXPERIMENTAL | Patients with poor- or intermediate-risk RCC with clear cell component for first-line treatment |
| Phase 1b Dose Escalation Cohort B | EXPERIMENTAL | Patients with favorable-risk RCC with clear cell component for first-line treatment. |
| MGCD516 | EXPERIMENTAL | MGCD516 oral capsule, administered in escalating doses in Phase 1, beginning with daily dosing and exploring other regimens as necessary, in 21 or 28 days cycles |
| Name | Type | Description |
|---|---|---|
| Sitravatinib | DRUG | Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases. |
| Nivolumab | DRUG | Nivolumab is a programmed death receptor-1 (PD-1) blocking antibody |
| Pembrolizumab | DRUG | Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody |
| Enfortumab Vedotin-Ejfv | DRUG | Enfortumab is a Nectin-4 directed antibody-drug conjugate (ADC) comprised of a monoclonal antibody conjugated to the small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) |
| Ipilimumab | DRUG | Ipilimumab is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking antibody |
| Warfarin | DRUG | CYP2C9 probe substrate |
| Dextromethorphan | DRUG | CYP2D6 probe substrate |
| Midazolam | DRUG | CYP3A4 probe substrate |
| Digoxin | DRUG | P-gp probe substrate |
| Rosuvastatin | DRUG | BCRP probe substrate |
| MGCD516 | DRUG | MGCD516 is a small molecule inhibitor of several closely related receptor tyrosine kinases. MGCD516 capsules will be taken with water. |
Inclusion Criteria: * Currently receiving sitravatinib single- agent or in combination with other therapeutic agent(s) in another Mirati- sponsored protocol * Currently tolerating the treatment regimen in the parent protocol * Experiencing clinical benefit with or without prior radiographic progres...
Sitravatinib is an investigational small molecule studied in advanced solid tumors, advanced or metastatic solid malignancies, clear cell renal cell carcinoma, and hepatic impairment. It has been evaluated in clinical trials both as a single agent and in combination with other anticancer therapies. It is not described as an approved therapy.
Sitravatinib is a small molecule kinase inhibitor belonging to the -tinib class. Kinase inhibitors act on enzymes that regulate cell signaling. The specific molecular target is not stated in the available information, so the precise kinase or kinases it inhibits cannot be confirmed here.
Sitravatinib is developed by Bristol-Myers Squibb Company, which trades under the ticker BMY. The company is listed as the developer of the sitravatinib clinical program across the solid tumor and hepatic impairment studies.
Sitravatinib is in clinical development. The program includes Phase 1 studies and a Phase 2 study, and the drug is investigational rather than approved. The Phase 2 trial, NCT04887870, evaluated sitravatinib with or without other anticancer therapies in patients receiving clinical benefit from a parent study.
Sitravatinib has been studied in completed trials including NCT04887870 in advanced or metastatic solid malignancies, NCT04887194, a Phase 1 drug-drug interaction and QTc study in advanced solid tumor, NCT04772612 in hepatic impairment, and NCT04518046 with nivolumab and ipilimumab in clear cell renal cell carcinoma or other solid malignancies.