Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Sitravatinib · 8 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.
Maximum observed plasma concentration
Area under the plasma concentration-time curve from time zero extrapolated to infinity
Area under the curve from time zero to the last measured time point
Terminal elimination half-life
Apparent total plasma clearance when dosed orally
Apparent volume of distribution when dosed orally
Unbound fraction
(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
Terminal elimination half-life
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. |
| Group 1 Treatment A | ACTIVE_COMPARATOR | A single-dose administration of sitravatinib malate 50 mg on Day 1. Day 12, a single dose of sitravatinib malate 50 mg will be will be followed by a 72-hour PK sample collection period. Subjects will be discharged from the CRU on Day 4 after collection of 72-hour postdose PK sample and completion of all required study procedures. |
| Group 1 Treatment B | ACTIVE_COMPARATOR | On Days 9 to 11, itraconazole 200 mg will be administered QD in the morning. On Day 12, a single dose of sitravatinib malate 50 mg will be coadministered with itraconazole. Itraconazole QD dosing will continue on Days 13 to 18 to maintain steady state during the PK sample collection period. |
| Group 2 Treatment A | ACTIVE_COMPARATOR | A single-dose administration of sitravatinib malate 100 mg on Day 1 will be followed by a 72-hour PK sample collection period. Subjects will be discharged from the CRU on Day 4 after collection of 72-hour postdose PK sample and completion of all required study procedures. |
| Group 2 Treatment B | ACTIVE_COMPARATOR | On Days 9 to 15, rifampin 600 mg will be administered QD in the morning. On Day 16, a single dose of sitravatinib malate 100 mg will be coadministered with rifampin followed by a 72 hour PK sample collection period. Rifampin QD dosing will continue on Days 17 to 22 to maintain steady state during the PK sample collection period. |
| Group 1 Treatment A (sitravatinib only) | EXPERIMENTAL | Period 1: A single oral dose of 100 mg sitravatinib on Day 1 |
| Group 1 Treatment B (sitravatinib and pantoprazole) | EXPERIMENTAL | Period 2: Oral pantoprazole once daily for 7 days (Days 1 to 7) and a single oral dose of 100 mg sitravatinib on Day 7 |
| Group 2 Treatment C (sitravatinib only) | EXPERIMENTAL | Period 1: A single oral dose of 100 mg sitravatinib on Day 1 |
| Group 2 Treatment D (sitravatinib and famotidine) | EXPERIMENTAL | Period 2: A single oral dose of 100 mg sitravatinib followed by a single oral dose of famotidine 40 mg approximately 2 hours after sitravatinib dose on Day 1 |
| 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. |
| Fasted dosing followed by fed dosing (high-fat meal) followed by fed dosing (low-fat meal) | EXPERIMENTAL | Dosing in the fasted state followed by fed dosing after high and low fat meals |
| Fasted dosing followed by fed dosing (low-fat meal) followed by fed dosing (high-fat meal) | EXPERIMENTAL | Dosing in the fasted state followed by fed dosing after low and high fat meals |
| Fed dosing (high-fat meal) followed by fasted dosing followed by fed dosing (low-fat meal) | EXPERIMENTAL | Dosing after a high-fat meal followed by doing in the fasted sate followed by dosing after a low-fat meal |
| Fed dosing (high-fat) followed by fed dosing (low-fat) followed by dosing in the fasted state | EXPERIMENTAL | Fed dosing (high-fate meal) followed by fed dosing (low-fate meal) followed by dosing in the fasted state |
| Fed dosing (low-fat) followed dosing in the fasted state followed by fed dosing (high fat) | EXPERIMENTAL | Fed dosing (low-fat) meal followed dosing in the fasted state followed by fed dosing (high-fat meal) |
| Fed dosing (low-fat) followed by fed dosing (high-fat) followed by dosing in the fasted state | EXPERIMENTAL | Fed dosing after a low-fat and high-fate meals followed by dosing in the fasted state |
| 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. |
| 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 |
| Sitravatinib 50 mg | DRUG | 50 mg Sitravatinib on Day 1 (Group 1A) |
| Sitravatinib 100 mg | DRUG | 100 mg Sitravatinib on Day 1 (Group 2A) |
| Itraconazole | DRUG | Itraconazole QD from Day 9 to Day 18, and Sitravatinib 50 mg at Day 12 (Group 1B) |
| Rifampin | DRUG | Rifampin QD from Day 9 to Day 22, and Sitravatinib 100 mg at Day 16 (Group 2B) |
| Pantoprazole | DRUG | 40 mg QD on Day 1 to Day 7 of Period 2 in Group 1 |
| Famotidine | DRUG | 40 mg PO 2 hrs after sitravatinib in Period 2 of Group 2 |
| 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 |
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 being studied in oncology. Clinical trials have evaluated it in advanced or metastatic solid malignancies, clear cell renal cell carcinoma, advanced solid tumors, and in healthy adults and patients with hepatic impairment for pharmacokinetic studies. It is not approved and remains in clinical development.
Sitravatinib is a small molecule receptor tyrosine kinase inhibitor. It is designed to inhibit multiple receptor tyrosine kinases involved in tumor growth and angiogenesis. The specific molecular targets have not been disclosed in the available clinical trial information.
Sitravatinib is being developed by Bristol-Myers Squibb Company, traded on the New York Stock Exchange under the ticker BMY. The company is conducting clinical trials of the drug in oncology indications.
Sitravatinib is in Phase 1 and Phase 2 clinical trials. The completed trials include Phase 1 studies in hepatic impairment and advanced solid tumors, and Phase 2 studies in clear cell renal cell carcinoma and advanced or metastatic solid malignancies. It is investigational and not FDA approved.
Sitravatinib has completed three clinical trials. NCT04772612 evaluated its pharmacokinetics in hepatic impairment, NCT04887194 assessed drug-drug interactions and QTc in advanced solid tumors, and NCT04887870 studied it with or without other anticancer therapies in advanced or metastatic solid malignancies. All trials were conducted in the United States.
Sitravatinib is a distinct investigational drug. No alternative names have been reported in the clinical trial records. It is being studied as a monotherapy and in combination with other anticancer therapies, such as nivolumab in clear cell renal cell carcinoma.