NCT03606174 · OUTCOME

Geometric Mean Blood Plasma Concentration of Sitravatinib

A Phase 2 Study of Sitravatinib in Combination With PD-(L)1 Checkpoint Inhibitor Regimens in Patients With Advanced or Metastatic Urothelial Carcinoma · Source last updated 2023-08-24

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure: GEOMETRIC_MEAN
Unit: ng/mL
Interval / dispersion: Geometric Coefficient of Variation
Time frame: Cycle(C)1 Day(D)1 pre-dose, 30min, 2,4,6,7,8,24hr post-dose, C1D15 pre-dose, 30min,2,4,6,7,8,24hr post-dose, C2D1 pre-dose,7hr post-dose, C2D8,C3D1,C3D8,C5D1,C6D8 pre-dose (28 day cycles Cohorts 1-8, 21 day cycles Cohort 9)

What was measured

Blood draws for analysis of blood plasma concentrations of sitravatinib were collected following electrocardiograms and assessment of vital signs. Concentration data below the limit of quantification were set to 0.

Analysis population: Measured in the Pharmacokinetic (PK) Evaluable Population, which included all participants who received treatment with sitravatinib and had available data at each timepoint. Per the statistical analysis plan (SAP), Cohort 9 arms are grouped as pre-specified as there was never intent to compare PK endpoints across Cohort 9 dose levels.

Groups in this outcome

Cohort 1

Participants with locally advanced or metastatic urothelial carcinoma (UC) with documented disease progression on or after previous anti-programmed cell death (PD)-ligand(L)-1 as most recent treatment, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 1. Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules once daily (QD) in 28-day cycles. Nivolumab was received via an intravenous (IV) infusion over approximately 30 minutes (± 5 minutes) at 240 mg once every 2 weeks (Q2W) or 480 mg once every 4 weeks (Q4W), at the discretion of the Investigator and in accordance with the current nivolumab US Prescribing Information (USPI).

Cohort 2

Participants with locally advanced or metastatic UC with documented disease progression on or after previous anti-PD-L-1 as most recent treatment, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 2. Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.

Cohort 3

Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 3. Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.

Cohort 4

Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti-PD-(L)1 as the most recent treatment, who previously received (in combination or separately) other selected immunotherapies, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 4. Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.

Cohort 5

Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 5. Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.

Cohort 6

Participants with locally advanced or metastatic UC who had not previously received an anti-PD-(L)1, and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 6. Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 120 mg capsules QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.

Cohort 7

Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and antibody-drug conjugate (ADC) (in combination or separately, and in any order), and who were previously treated with a platinum-based chemotherapy were enrolled into Cohort 7. Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.

Cohort 8

Participants with locally advanced or metastatic UC with documented disease progression on or after a previous anti PD-(L)1 and ADC (in combination or separately, and in any order), and who were considered ineligible for platinum-based chemotherapy were enrolled into Cohort 8. Participants received sitravatinib in combination with nivolumab. Sitravatinib was received orally via 100 mg malate capsules, or 120 mg free base capsule formulation QD in 28-day cycles. Nivolumab was received via an IV infusion over approximately 30 minutes (± 5 minutes) at 240 mg Q2W or 480 mg Q4W, at the discretion of the Investigator and in accordance with the current nivolumab USPI.

Cohort 9

Participants with locally advanced or metastatic UC who had previously received a PD-(L)1 checkpoint inhibitor (CPI) and a platinum-based chemotherapy were enrolled into Cohort 9, which included a lead-in dose-escalation part. A dose-expansion part was planned, but was not enrolled. During the lead-in dose-escalation part, participants were enrolled to 3 dose levels of sitravatinib in combination with pembrolizumab and enfortumab vedotin. Sitravatinib was received orally via capsules QD in 21-day cycles at doses 35 mg and 70 mg. Pembrolizumab was received as an IV infusion over approximately 30 minutes (± 5 minutes) at 200 mg every 3 weeks (Q3W), in accordance with the current pembrolizumab USPI. Enfortumab vedotin dosing was based on participant weight, starting at 1.25 mg/kg up to 125 mg/kg QD, with a dose de-escalation step to 1 mg/kg. Enfortumab vedotin was received as an IV infusion over approximately 30 minutes (± 5 minutes) on Days 1 and 8 of a 21-day cycle.

Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.