Skip to content
Triangle logo TriangleGet started
← Full study record

NCT03606174 · OUTCOME

Progression-Free Survival (PFS)

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
MEDIAN
Unit
months
Interval / dispersion
95% Confidence Interval
Time frame
Up to approximately 3 years

What was measured

PFS was defined as the time from date of first study treatment to first PD per RECIST V1.1, or death due to any cause in the absence of documented PD.

Analysis population: Measured in the Full Analysis Set, which included participants who received ≥ 1 dose of each study treatment drug (ie, ≥ 1 dose of both sitravatinib and nivolumab for Cohorts 1 to 8, or ≥ 1 dose each of sitravatinib, pembrolizumab, and enfortumab vedotin for Cohort 9). Per the statistical analysis plan (SAP), Cohort 9 arms are grouped as pre-specified as there was never intent to compare efficacy 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.

Analysis denominator · Participants

GroupSource count
Cohort 149
Cohort 223
Cohort 318
Cohort 49
Cohort 553
Cohort 627
Cohort 756
Cohort 89
Cohort 916

Reported measurements

Source class 1
Values in months · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Cohort 13.877Not reported2.4975.487Not reported
Cohort 27.786Not reported3.94314.620Not reported
Cohort 33.910Not reported1.8739.133Not reported
Cohort 43.515Not reported1.971NAUpper confidence intervals could not be calculated due to the low number of participants with a documented PD or death.
Cohort 53.943Not reported3.4505.651Not reported
Cohort 65.421Not reported3.22018.168Not reported
Cohort 73.680Not reported2.2345.520Not reported
Cohort 83.713Not reported1.840NAUpper confidence intervals could not be calculated due to the low number of participants with a documented PD or death.
Cohort 94.0Not reported2.046.51Not reported
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        2.497
        upper Limit
        5.487
        value
        3.877
      2. group Id
        OG001
        lower Limit
        3.943
        upper Limit
        14.620
        value
        7.786
      3. group Id
        OG002
        lower Limit
        1.873
        upper Limit
        9.133
        value
        3.910
      4. comment
        Upper confidence intervals could not be calculated due to the low number of participants with a documented PD or death.
        group Id
        OG003
        lower Limit
        1.971
        upper Limit
        NA
        value
        3.515
      5. group Id
        OG004
        lower Limit
        3.450
        upper Limit
        5.651
        value
        3.943
      6. group Id
        OG005
        lower Limit
        3.220
        upper Limit
        18.168
        value
        5.421
      7. group Id
        OG006
        lower Limit
        2.234
        upper Limit
        5.520
        value
        3.680
      8. comment
        Upper confidence intervals could not be calculated due to the low number of participants with a documented PD or death.
        group Id
        OG007
        lower Limit
        1.840
        upper Limit
        NA
        value
        3.713
      9. group Id
        OG008
        lower Limit
        2.04
        upper Limit
        6.51
        value
        4.0
denoms
  1. counts
    1. group Id
      OG000
      value
      49
    2. group Id
      OG001
      value
      23
    3. group Id
      OG002
      value
      18
    4. group Id
      OG003
      value
      9
    5. group Id
      OG004
      value
      53
    6. group Id
      OG005
      value
      27
    7. group Id
      OG006
      value
      56
    8. group Id
      OG007
      value
      9
    9. group Id
      OG008
      value
      16
    units
    Participants
description
PFS was defined as the time from date of first study treatment to first PD per RECIST V1.1, or death due to any cause in the absence of documented PD.
dispersion Type
95% Confidence Interval
groups
  1. description
    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).
    id
    OG000
    title
    Cohort 1
  2. description
    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.
    id
    OG001
    title
    Cohort 2
  3. description
    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.
    id
    OG002
    title
    Cohort 3
  4. description
    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.
    id
    OG003
    title
    Cohort 4
  5. description
    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.
    id
    OG004
    title
    Cohort 5
  6. description
    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.
    id
    OG005
    title
    Cohort 6
  7. description
    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.
    id
    OG006
    title
    Cohort 7
  8. description
    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.
    id
    OG007
    title
    Cohort 8
  9. description
    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.
    id
    OG008
    title
    Cohort 9
param Type
MEDIAN
population Description
Measured in the Full Analysis Set, which included participants who received ≥ 1 dose of each study treatment drug (ie, ≥ 1 dose of both sitravatinib and nivolumab for Cohorts 1 to 8, or ≥ 1 dose each of sitravatinib, pembrolizumab, and enfortumab vedotin for Cohort 9). Per the statistical analysis plan (SAP), Cohort 9 arms are grouped as pre-specified as there was never intent to compare efficacy endpoints across Cohort 9 dose levels.
reporting Status
POSTED
time Frame
Up to approximately 3 years
title
Progression-Free Survival (PFS)
type
SECONDARY
unit Of Measure
months

Download exact source JSON → · Snapshot ctgov-results-25a395029948b04d52b1253f

Preserved source evidence · Not medical advice