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NCT03606174 · OUTCOME

Duration of Response (DOR)

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

DOR was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of objective progression of disease (PD) per RECIST V1.1, or to death due to any cause in the absence of documented PD. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis \< 10 mm). PR was defined as a greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm. 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.

Analysis population: Measured in the Clinical Activity Evaluable Population-confirmed Response Subset, which included participants who achieved an objective response, received ≥1 dose of study treatment drug, had an evaluable baseline tumor assessment and ≥1 post-baseline tumor assessment. One participant in Cohort 6 who experienced a response wasn't included in DOR analysis because they didn't receive ≥1 dose of study treatment, have an evaluable baseline tumor assessment or ≥1 post-baseline tumor assessment.

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 16
Cohort 25
Cohort 34
Cohort 40
Cohort 517
Cohort 68
Cohort 73
Cohort 80
Cohort 94

Reported measurements

Source class 1
Values in months · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Cohort 15.585Not reported3.844NAUpper confidence intervals could not be calculated due to the low number of participants with a response.
Cohort 29.478Not reported5.782NAUpper confidence intervals could not be calculated due to the low number of participants with a response.
Cohort 311.762Not reported7.392NAUpper confidence intervals could not be calculated due to the low number of participants with a response.
Cohort 57.326Not reported5.52012.977Not reported
Cohort 616.361Not reported5.552NAUpper confidence intervals could not be calculated due to the low number of participants with a response.
Cohort 77.425Not reported5.552NAUpper confidence intervals could not be calculated due to the low number of participants with a response.
Cohort 911.8Not reported4.70NAUpper confidence intervals could not be calculated due to the low number of participants with a response.
Complete source fields
classes
  1. categories
    1. measurements
      1. comment
        Upper confidence intervals could not be calculated due to the low number of participants with a response.
        group Id
        OG000
        lower Limit
        3.844
        upper Limit
        NA
        value
        5.585
      2. comment
        Upper confidence intervals could not be calculated due to the low number of participants with a response.
        group Id
        OG001
        lower Limit
        5.782
        upper Limit
        NA
        value
        9.478
      3. comment
        Upper confidence intervals could not be calculated due to the low number of participants with a response.
        group Id
        OG002
        lower Limit
        7.392
        upper Limit
        NA
        value
        11.762
      4. group Id
        OG004
        lower Limit
        5.520
        upper Limit
        12.977
        value
        7.326
      5. comment
        Upper confidence intervals could not be calculated due to the low number of participants with a response.
        group Id
        OG005
        lower Limit
        5.552
        upper Limit
        NA
        value
        16.361
      6. comment
        Upper confidence intervals could not be calculated due to the low number of participants with a response.
        group Id
        OG006
        lower Limit
        5.552
        upper Limit
        NA
        value
        7.425
      7. comment
        Upper confidence intervals could not be calculated due to the low number of participants with a response.
        group Id
        OG008
        lower Limit
        4.70
        upper Limit
        NA
        value
        11.8
denoms
  1. counts
    1. group Id
      OG000
      value
      6
    2. group Id
      OG001
      value
      5
    3. group Id
      OG002
      value
      4
    4. group Id
      OG003
      value
      0
    5. group Id
      OG004
      value
      17
    6. group Id
      OG005
      value
      8
    7. group Id
      OG006
      value
      3
    8. group Id
      OG007
      value
      0
    9. group Id
      OG008
      value
      4
    units
    Participants
description
DOR was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of objective progression of disease (PD) per RECIST V1.1, or to death due to any cause in the absence of documented PD. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis \< 10 mm). PR was defined as a greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm. 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.
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 Clinical Activity Evaluable Population-confirmed Response Subset, which included participants who achieved an objective response, received ≥1 dose of study treatment drug, had an evaluable baseline tumor assessment and ≥1 post-baseline tumor assessment. One participant in Cohort 6 who experienced a response wasn't included in DOR analysis because they didn't receive ≥1 dose of study treatment, have an evaluable baseline tumor assessment or ≥1 post-baseline tumor assessment.
reporting Status
POSTED
time Frame
Up to approximately 3 years
title
Duration of Response (DOR)
type
SECONDARY
unit Of Measure
months

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

Preserved source evidence · Not medical advice