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

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).

Total of all reporting groups

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

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.

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).

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.

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.

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.

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

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.

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.

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

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.

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

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.

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.

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.

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

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.

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

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.

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

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.

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

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.

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.

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.

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).

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.

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).