Trial Outcomes & Findings for Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma (NCT NCT03680521)

Last Updated: 2023-10-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Results posted on

2023-10-04

Participant Flow

After the participants completed screening, participants underwent an initial diagnostic tumor biopsy of their renal lesion. Out of the 25 participants enrolled, 5 participants did not receive treatment per protocol. The reasons were ineligible histology (3), disallowed concomitant treatment (1), and patient noncompliance (1).

Participant milestones

Participant milestones
Measure	Sitravatinib 120 mg 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 80 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).
Overall Study STARTED	7	13
Overall Study COMPLETED	7	13
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitravatinib 120 mg n=7 Participants 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 80 mg n=13 Participants 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).	Total n=20 Participants Total of all reporting groups
Age, Continuous	63.4 years STANDARD_DEVIATION 6.19 • n=5 Participants	56.7 years STANDARD_DEVIATION 12.70 • n=7 Participants	59.1 years STANDARD_DEVIATION 11.18 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	11 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	7 Participants n=5 Participants	12 Participants n=7 Participants	19 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Clinical TNM Staging at Diagnosis T2bN0M0	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Clinical TNM Staging at Diagnosis T3N0M0	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Clinical TNM Staging at Diagnosis T3N0M1	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Clinical TNM Staging at Diagnosis T3NXM0	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Clinical TNM Staging at Diagnosis T3aN0M0	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Clinical TNM Staging at Diagnosis T3aNXM0	0 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants
Clinical TNM Staging at Diagnosis T3aNXM1	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Population: 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.

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=6 Participants 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 80 mg n=11 Participants 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).	PK Population: Sitravatinib 60 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.
Percentage of Participants Who Achieved a Point in Time Objective Response (Either Complete or Partial Response [CR or PR]) Prior to Surgery	2 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

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.

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=6 Participants 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 80 mg n=11 Participants 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).	PK Population: Sitravatinib 60 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.
Point in Time Objective Response Prior to Surgery Preoperative timepoint response: SD	4 Participants	11 Participants	—
Point in Time Objective Response Prior to Surgery Preoperative timepoint response: CR	0 Participants	0 Participants	—
Point in Time Objective Response Prior to Surgery Preoperative timepoint response: PR	2 Participants	0 Participants	—
Point in Time Objective Response Prior to Surgery Preoperative timepoint response: PD	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)

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

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.

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=7 Participants 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 80 mg n=13 Participants 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).	PK Population: Sitravatinib 60 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.
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	7 Participants	13 Participants	—

SECONDARY outcome

Timeframe: Day 1 (pre-dose, and 30 minutes and 4 hours post-dose), Day 15 (pre-dose) and Day 43 (pre-dose)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=7 Participants 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 80 mg n=13 Participants 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).	PK Population: Sitravatinib 60 mg n=1 Participants 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.
Blood Plasma Concentrations of Sitravatinib Day 1 (pre-dose)	0.0 ng/mL Standard Deviation 0.00	0.6 ng/mL Standard Deviation 2.27	—
Blood Plasma Concentrations of Sitravatinib Day 1 (30 mins post-dose)	2.9 ng/mL Standard Deviation 2.12	1.0 ng/mL Standard Deviation 1.17	—
Blood Plasma Concentrations of Sitravatinib Day 1 (4 hours post-dose)	17.0 ng/mL Standard Deviation 10.38	13.7 ng/mL Standard Deviation 10.60	—
Blood Plasma Concentrations of Sitravatinib Day 15 (pre-dose)	87.7 ng/mL Standard Deviation 9.62	63.3 ng/mL Standard Deviation 42.36	—
Blood Plasma Concentrations of Sitravatinib Day 43 (pre-dose)	75.0 ng/mL Standard Deviation 23.74	53.7 ng/mL Standard Deviation 32.88	66.5 ng/mL Standard Deviation NA Only 1 participant received 60 mg, so standard deviation (SD) could not be calculated.

SECONDARY outcome

Timeframe: Day 1 up to date of surgery (maximum time to surgery was approximately 13 weeks)

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

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=6 Participants 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 80 mg n=11 Participants 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).	PK Population: Sitravatinib 60 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.
Time to Surgery Time to Surgery	56.5 days Interval 46.0 to 61.0	50.0 days Interval 46.0 to 55.0	—
Time to Surgery Delays in Surgery	1.0 days Interval 1.0 to 4.0	1.0 days Interval 1.0 to 39.0	—

SECONDARY outcome

Timeframe: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks)

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

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=6 Participants 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 80 mg n=11 Participants 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).	PK Population: Sitravatinib 60 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.
Disease Free Survival (DFS)	NA months Interval 32.13 to Median and upper confidence interval data could not be analyzed because too few participants experienced an event of disease recurrence or death.	NA months Interval 18.56 to Median and upper confidence interval data could not be analyzed because too few participants experienced an event of disease recurrence or death.	—

SECONDARY outcome

Timeframe: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Population: 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. Tumor tissue was used to assess the mean PD-L1 expression in the tumor via immunohistochemistry and/or immunofluorescence.

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=5 Participants 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 80 mg n=8 Participants 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).	PK Population: Sitravatinib 60 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.
Percentage Change From Baseline in Programmed Death Ligand 1 (PD-L1) Expression in the Tumor	1.6 percentage change in PD-L1 expression Standard Deviation 2.07	2.5 percentage change in PD-L1 expression Standard Deviation 7.07	—

SECONDARY outcome

Timeframe: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

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

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=2 Participants 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 80 mg n=3 Participants 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).	PK Population: Sitravatinib 60 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.
Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor	34.5 cells/mm^2 Standard Deviation 72.41	-55.1 cells/mm^2 Standard Deviation 151.11	—

SECONDARY outcome

Timeframe: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

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

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=2 Participants 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 80 mg n=3 Participants 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).	PK Population: Sitravatinib 60 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.
Change From Baseline in Regulatory T-cells (Tregs) in the Tumor	-24.1 cells/mm^2 Standard Deviation 45.86	49.6 cells/mm^2 Standard Deviation 43.62	—

SECONDARY outcome

Timeframe: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

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

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=2 Participants 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 80 mg n=3 Participants 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).	PK Population: Sitravatinib 60 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.
Change From Baseline in CD4+ T-cells in the Tumor	-114.1 cells/mm^2 Standard Deviation 144.72	111.2 cells/mm^2 Standard Deviation 231.86	—

SECONDARY outcome

Timeframe: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

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

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=2 Participants 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 80 mg n=3 Participants 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).	PK Population: Sitravatinib 60 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.
Change From Baseline in CD8+ T-cells in the Tumor	-88.3 cells/mm^2 Standard Deviation 164.13	30.9 cells/mm^2 Standard Deviation 181.86	—

SECONDARY outcome

Timeframe: Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

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.

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=2 Participants 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 80 mg n=3 Participants 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).	PK Population: Sitravatinib 60 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.
Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor	-1.9 ratio Standard Deviation 2.28	-1.1 ratio Standard Deviation 1.15	—

SECONDARY outcome

Timeframe: Baseline to Day 43

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).

Outcome measures

Outcome measures
Measure	Sitravatinib 120 mg n=6 Participants 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 80 mg n=8 Participants 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).	PK Population: Sitravatinib 60 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.
Change From Baseline of Selected Cytokines in Peripheral Blood sPD-1	3.6 pg/ml Standard Deviation 19.59	3.8 pg/ml Standard Deviation 12.49	—
Change From Baseline of Selected Cytokines in Peripheral Blood Eotaxin	3.1 pg/ml Standard Deviation 12.91	3.4 pg/ml Standard Deviation 12.48	—
Change From Baseline of Selected Cytokines in Peripheral Blood sCD27	-78.6 pg/ml Standard Deviation 755.97	-30.3 pg/ml Standard Deviation 567.82	—
Change From Baseline of Selected Cytokines in Peripheral Blood MIP-1b	10.6 pg/ml Standard Deviation 20.33	1.9 pg/ml Standard Deviation 6.58	—

Adverse Events

Sitravatinib 120 mg

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Sitravatinib 80 mg

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sitravatinib 120 mg n=7 participants at risk 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 80 mg n=13 participants at risk 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).
Infections and infestations Atypical pneumonia	0.00% 0/7 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)	7.7% 1/13 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)
Infections and infestations Sepsis	0.00% 0/7 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)	7.7% 1/13 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)
Infections and infestations Urosepsis	14.3% 1/7 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)	0.00% 0/13 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)
Cardiac disorders Atrial fibrillation	14.3% 1/7 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)	0.00% 0/13 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)
Renal and urinary disorders Urinary retention	14.3% 1/7 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)	0.00% 0/13 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/7 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)	7.7% 1/13 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)
Vascular disorders Deep vein thrombosis	0.00% 0/7 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)	7.7% 1/13 • All cause mortality: Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks); serious and other adverse events: Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)

Other adverse events

Additional Information

Sr. Clinical Operations Trial Manager

Mirati Therapeutics

Phone: 858-332-3540

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place