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NCT03606174 · OUTCOME

Number of Participants Who Experienced a Serious Adverse Event (SAE)

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
COUNT_OF_PARTICIPANTS
Unit
Participants
Interval / dispersion
Not reported
Time frame
Day 1 up to approximately 3 years

What was measured

An SAE was defined as any event that resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/permanent damage (substantial disruption of the ability to conduct normal life functions), a congenital anomaly/birth defect, or may have jeopardized the participant and may have required medical or surgical intervention to prevent intensive treatment in an emergency room or at home (e.g. for allergic bronchospasm, blood dyscrasias or convulsions) that do not result in inpatient hospitalization, development of drug dependency or drug abuse.

Analysis population: Measured in the safety population, which included all participants who received ≥ 1 dose of any study treatment (sitravatinib, nivolumab, pembrolizumab, or enfortumab vedotin).

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 Dose Level 1

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 in Cohort 9 Dose Level 1 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.25 mg/kg IV infusion on Days 1 and 8 every 3 weeks (Q3W), and pembrolizumab 200 mg Q3W as an IV infusion.

Cohort 9 Dose Level 2

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 in Cohort 9 Dose Level 2 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.

Cohort 9 Dose Level 3

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 in Cohort 9 Dose Level 3 were enrolled to receive sitravatinib 70 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.

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 9 Dose Level 18
Cohort 9 Dose Level 24
Cohort 9 Dose Level 34

Reported measurements

Source class 1
Values in Participants · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
Cohort 135Not reportedNot reportedNot reportedNot reported
Cohort 215Not reportedNot reportedNot reportedNot reported
Cohort 310Not reportedNot reportedNot reportedNot reported
Cohort 44Not reportedNot reportedNot reportedNot reported
Cohort 526Not reportedNot reportedNot reportedNot reported
Cohort 614Not reportedNot reportedNot reportedNot reported
Cohort 723Not reportedNot reportedNot reportedNot reported
Cohort 83Not reportedNot reportedNot reportedNot reported
Cohort 9 Dose Level 15Not reportedNot reportedNot reportedNot reported
Cohort 9 Dose Level 21Not reportedNot reportedNot reportedNot reported
Cohort 9 Dose Level 33Not reportedNot reportedNot reportedNot reported
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        value
        35
      2. group Id
        OG001
        value
        15
      3. group Id
        OG002
        value
        10
      4. group Id
        OG003
        value
        4
      5. group Id
        OG004
        value
        26
      6. group Id
        OG005
        value
        14
      7. group Id
        OG006
        value
        23
      8. group Id
        OG007
        value
        3
      9. group Id
        OG008
        value
        5
      10. group Id
        OG009
        value
        1
      11. group Id
        OG010
        value
        3
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
      8
    10. group Id
      OG009
      value
      4
    11. group Id
      OG010
      value
      4
    units
    Participants
description
An SAE was defined as any event that resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/permanent damage (substantial disruption of the ability to conduct normal life functions), a congenital anomaly/birth defect, or may have jeopardized the participant and may have required medical or surgical intervention to prevent intensive treatment in an emergency room or at home (e.g. for allergic bronchospasm, blood dyscrasias or convulsions) that do not result in inpatient hospitalization, development of drug dependency or drug abuse.
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 in Cohort 9 Dose Level 1 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.25 mg/kg IV infusion on Days 1 and 8 every 3 weeks (Q3W), and pembrolizumab 200 mg Q3W as an IV infusion.
    id
    OG008
    title
    Cohort 9 Dose Level 1
  10. 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 in Cohort 9 Dose Level 2 were enrolled to receive sitravatinib 35 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
    id
    OG009
    title
    Cohort 9 Dose Level 2
  11. 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 in Cohort 9 Dose Level 3 were enrolled to receive sitravatinib 70 mg QD orally via capsules in 21-day cycles, enfortumab vedotin 1.0 mg/kg IV infusion on Days 1 and 8 Q3W, and pembrolizumab 200 mg Q3W as an IV infusion.
    id
    OG010
    title
    Cohort 9 Dose Level 3
param Type
COUNT_OF_PARTICIPANTS
population Description
Measured in the safety population, which included all participants who received ≥ 1 dose of any study treatment (sitravatinib, nivolumab, pembrolizumab, or enfortumab vedotin).
reporting Status
POSTED
time Frame
Day 1 up to approximately 3 years
title
Number of Participants Who Experienced a Serious Adverse Event (SAE)
type
SECONDARY
unit Of Measure
Participants

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

Preserved source evidence · Not medical advice