Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Nivolumab

Tyrosine Kinase Inhibitors

Immunologic Factors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Tyrosine

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.

Sitravatinib oral capsule administered daily for 6-8 weeks in segments 1 and 2.

Sitravatinib

Nivolumab administered as 240 mg IV every 2 weeks for 4-6 weeks in segment 2.

The study will evaluate the clinical activity of sitravatinib in combination with nivolumab in patients with locally-advanced clear cell renal cell carcinoma (ccRCC) in the neoadjuvant setting prior to nephrectomy.

Sitravatinib is a receptor tyrosine kinase inhibitor (TKI) that targets multiple closely related receptor tyrosine kinase pathways including VEGFR, PDGFR, c-KIT, MET, and the TAM family of receptors (TYRO3, AXL, and MER). Nivolumab is a monoclonal antibody directed against PD-1 and blocks the interaction between PD-1 and its ligands, thereby releasing PD-1-mediated inhibition of T-cell proliferation (including cytotoxic CD8+ T-cells) and cytokine production. Together, sitravatinib and nivolumab may cooperate to elicit greater anti-tumor activity than either agent alone, as sitravatinib is predicted to enhance several steps in the cancer immunity cycle that may augment the efficacy of nivolumab.

Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma

A Phase 2 Study of Sitravatinib in Combination With Nivolumab in Patients Undergoing Nephrectomy for Locally-Advanced Clear Cell Renal Cell Carcinoma

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.

TEAEs occured after the first dose of any study treatment or any preexisting condition that increased in severity after the first dose of study treatment and prior to 28 days after last dose of study drug or surgery, whichever occurred last.

TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

The blood plasma concentrations of sitravatinib were determined using blood samples. Blood samples for analysis of blood plasma concentrations of sitravatinib were taken after scheduled vital signs and triplicate electrocardiogram assessments.

Time to surgery was defined as the number of calendar days between Day 1 and the planned nephrectomy.

DFS was defined as the time from date of surgery to disease recurrence or death whichever occurred first.

Tumor tissue was collected from study biopsies and surgical samples. Tumor tissue was used to assess the mean PD-L1 expression in the tumor via immunohistochemistry and/or immunofluorescence.

Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean MDSCs using immunohistochemistry.

Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean Tregs using immunohistochemistry.

Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD4+ T-cells using immunohistochemistry.

Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD8+ T-cells using immunohistochemistry.

Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean ratio of Type 1 to Type 2 tumor associated macrophages using immunohistochemistry.

Cytokines measured in peripheral blood were soluble CD27 (sCD27), eotaxin, macrophage inflammatory protein 1b (MIP-1b), and soluble programmed cell death protein 1 (sPD-1).

Mirati Therapeutics Inc.

Participants received sitravatinib orally, once a day, at a dose of 120 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).

Sitravatinib 120 mg

Participants received sitravatinib orally, once a day, at a dose of 80 mg for 2 weeks (segment 1). Then, the participants continued to receive sitravatinib in combination with nivolumab 240 mg administered as an intravenous (IV) infusion every 2 weeks, for a maximum of 6 additional weeks (segment 2).

Sitravatinib 80 mg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

EGOG performance status was measured on a 6 point scale to assess participant's performance status.

0: Fully active, able to carry on all pre-disease performance without restriction

1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

Eastern Cooperative Oncology Group (ECOG) Performance Status

T = Size of original tumour, classed from T0 to T4; N = Degree of spread to lymph nodes classed from N0 to N3; M = Presence of distant metastasis classed as M0 to M1. X denotes uncertainty in assigning a given category (T, N, or M) when all reasonable clinical or pathologic maneuvers have been used in staging.

Clinical TNM Staging at Diagnosis

Safety population: all participants who received at least 1 dose of either sitravatinib or nivolumab.

Sr. Clinical Operations Trial Manager

Clinical activity evaluable population: All participants who 1) had measurable disease (per RECIST 1.1) at baseline, 2) received at least one dose of both sitravatinib and nivolumab, 3) had their onstudy disease assessment prior to surgery, and 4) underwent surgery and were deemed disease-free (i.e. non-metastatic) after surgery.

Percentage of Participants Who Achieved a Point in Time Objective Response (Either Complete or Partial Response [CR or PR]) Prior to Surgery

Preoperative timepoint response: CR

Preoperative timepoint response: PR

Preoperative timepoint response: SD

Preoperative timepoint response: PD

Point in Time Objective Response Prior to Surgery

Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

Day 1 (pre-dose)

Day 1 (30 mins post-dose)

Day 1 (4 hours post-dose)

Day 15 (pre-dose)

Day 43 (pre-dose)

PK assessments were assessed based on the actual dose associated with the visit. The PK assessment was associated with a daily dose of 120 mg of sitravatinib orally.

PK Population: Sitravatinib 120 mg

PK assessments were assessed based on the actual dose associated with the visit. The PK assessment was associated with a daily dose of 80 mg of sitravatinib orally.

PK Population: Sitravatinib 80 mg

PK assessments were assessed based on the actual dose associated with the visit. The PK assessment was associated with a daily dose of 60 mg of sitravatinib orally. This participant was randomized to sitravatinib 120 mg arm, but received sitravatinib 60 mg at Day 43.

PK Population: Sitravatinib 60 mg

Pharmacokinetics (PK) evaluable population: all participants who received treatment with sitravatinib and had non-missing concentration-time data. Concentration was assessed by actual dose associated with each time-point. One participant was randomized to sitravatinib 120 mg arm, but received sitravatinib 60 mg at Day 43.

Blood Plasma Concentrations of Sitravatinib

Time to Surgery

Delays in Surgery

Disease Free Survival (DFS)

Pharmacodynamic evaluable population: all participants who received at least 1 dose of sitravatinib or nivolumab for whom sufficient pharmacodynamic data were available for analysis of the endpoint.

Spots Global Cancer Trial Database for tam rtks

Every month we try and update this database with for tam rtks cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for tam rtks

Every month we try and update this database with for tam rtks cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for tam rtks cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.