Brief Summary
The purpose of this study is to measure the effect of IPI-549 in combination with nivolumab when compared to nivolumab monotherapy in advanced urothelial cancer patients.
Brief Title
Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)
Detailed Description
Study IPI-549-02 is a multi-national, prospective, randomized, active-control Phase II trial to evaluate the efficacy and safety of IPI 549 administered in combination with nivolumab compared to nivolumab monotherapy.
The study will enroll approximately 160 checkpoint-naïve, advanced urothelial cancer patients who have progressed or recurred following treatment with platinum-based chemotherapy. Patients will be randomized 2:1 to receive intravenous (IV) nivolumab 480 mg every 4 weeks (Q4W) in combination with oral (PO) IPI 549 40 mg once daily (QD) or IV nivolumab 480 mg Q4W in combination with placebo PO QD.
Eligible patients who have confirmed progression of disease during treatment with nivolumab monotherapy may crossover to the combination treatment arm.
The study will enroll approximately 160 checkpoint-naïve, advanced urothelial cancer patients who have progressed or recurred following treatment with platinum-based chemotherapy. Patients will be randomized 2:1 to receive intravenous (IV) nivolumab 480 mg every 4 weeks (Q4W) in combination with oral (PO) IPI 549 40 mg once daily (QD) or IV nivolumab 480 mg Q4W in combination with placebo PO QD.
Eligible patients who have confirmed progression of disease during treatment with nivolumab monotherapy may crossover to the combination treatment arm.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Bladder Cancer
Urothelial Carcinoma
Solid Tumor
Advanced Cancer
Eligibility Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra
* Measurable disease by CT or MRI as defined by RECIST v1.1
* Disease progression or recurrence after treatment:
* i) With at least 1 platinum-based chemotherapy regimen for the treatment of metastatic (Stage IV) or locally advanced unresectable disease; or
* ii) With disease recurrence within 1 year of completing a platinum-based neoadjuvant or adjuvant therapy
* Subject that have received more than 2 prior lines of chemotherapy must not have liver metastases
* Tumor tissues (archived or new biopsy) must be provided for biomarker analysis
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* Blood sample must be provided for mMDSC levels for randomization into the study
Exclusion Criteria:
* Active brain metastases or leptomeningeal metastases
* Any serious or uncontrolled medical disorder that may interfere with study treatment/interpretation
* Prior malignancy active within the previous 3 years except for local or organ confined early stage cancer that has been apparently cured
* Active, known, or suspected autoimmune disease
* A condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration
* Prior therapy with anti-tumor vaccines, any T cell co-stimulation or checkpoint pathways, or IPI-549
* Prior surgery or gastrointestinal dysfunction that may affect drug absorption
* Past medical history of interstitial lung disease
* History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control
* Positive test for hepatitis B, C or HIV
* Dependent on continuous supplemental oxygen
* Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra
* Measurable disease by CT or MRI as defined by RECIST v1.1
* Disease progression or recurrence after treatment:
* i) With at least 1 platinum-based chemotherapy regimen for the treatment of metastatic (Stage IV) or locally advanced unresectable disease; or
* ii) With disease recurrence within 1 year of completing a platinum-based neoadjuvant or adjuvant therapy
* Subject that have received more than 2 prior lines of chemotherapy must not have liver metastases
* Tumor tissues (archived or new biopsy) must be provided for biomarker analysis
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* Blood sample must be provided for mMDSC levels for randomization into the study
Exclusion Criteria:
* Active brain metastases or leptomeningeal metastases
* Any serious or uncontrolled medical disorder that may interfere with study treatment/interpretation
* Prior malignancy active within the previous 3 years except for local or organ confined early stage cancer that has been apparently cured
* Active, known, or suspected autoimmune disease
* A condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration
* Prior therapy with anti-tumor vaccines, any T cell co-stimulation or checkpoint pathways, or IPI-549
* Prior surgery or gastrointestinal dysfunction that may affect drug absorption
* Past medical history of interstitial lung disease
* History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control
* Positive test for hepatitis B, C or HIV
* Dependent on continuous supplemental oxygen
Inclusion Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra
* Measurable disease by CT or MRI as defined by RECIST v1.1
* Disease progression or recurrence after treatment:
* i) With at least 1 platinum-based chemotherapy regimen for the treatment of metastatic (Stage IV) or locally advanced unresectable disease; or
* ii) With disease recurrence within 1 year of completing a platinum-based neoadjuvant or adjuvant therapy
* Subject that have received more than 2 prior lines of chemotherapy must not have liver metastases
* Tumor tissues (archived or new biopsy) must be provided for biomarker analysis
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* Blood sample must be provided for mMDSC levels for randomization into the study
* Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra
* Measurable disease by CT or MRI as defined by RECIST v1.1
* Disease progression or recurrence after treatment:
* i) With at least 1 platinum-based chemotherapy regimen for the treatment of metastatic (Stage IV) or locally advanced unresectable disease; or
* ii) With disease recurrence within 1 year of completing a platinum-based neoadjuvant or adjuvant therapy
* Subject that have received more than 2 prior lines of chemotherapy must not have liver metastases
* Tumor tissues (archived or new biopsy) must be provided for biomarker analysis
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* Blood sample must be provided for mMDSC levels for randomization into the study
Gender
All
Gender Based
false
Keywords
eganelisib
IPI-549
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03980041
Org Class
Industry
Org Full Name
Infinity Pharmaceuticals, Inc.
Org Study Id
IPI-549-02
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2, Multicenter, Randomized, Double-Blind, Active-Control Study to Evaluate the Efficacy and Safety of Nivolumab Administered in Combination With IPI-549 Compared to Nivolumab Monotherapy in the Treatment of Patients With Immune Therapy-Naïve, Advanced Urothelial Carcinoma
Primary Outcomes
Outcome Description
ORR is defined as best response of complete response (CR) or partial response (PR) as measured by RECIST v1.1.
RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \<10 mm in short axis. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
RECIST 1.1 = Response Evaluation Criteria in Solid Tumors. CR= Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \<10 mm in short axis. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Outcome Measure
Objective Response Rate (ORR) per RECISTv1.1
Outcome Time Frame
First dosing date to date of confirmed disease progression, assessed up to 24 months
Secondary Outcomes
Outcome Description
TTR is defined as the time from the first dose of study treatment to first objective response \[complete response (CR) or partial response (PR)\] in patients with CR or PR.
Outcome Time Frame
First dosing date to date of first objective response, assessed up to 24 months
Outcome Measure
Time to Response (TTR)
Outcome Description
DOR is defined as the time from the first objective response (CR or PR) to documented disease progression in patients with CR or PR.
Outcome Time Frame
Date of first objective response to date of confirmed disease progression, assessed up to 24 months
Outcome Measure
Duration of Response (DOR)
Outcome Description
PFS is defined as the time from the first dose of study treatment to documented disease progression or death due to any cause.
Outcome Time Frame
First dosing to date to confirmed disease progression or death, assessed up to 48 months
Outcome Measure
Progression-Free Survival (PFS)
Outcome Description
If TSH result is abnormal, subsequent testing of Free T3 and free T4 required.
Outcome Time Frame
Pre-treatment (within 7 days of first dose) to date of confirmed disease progression, assessed up to 24 months
Outcome Measure
Changes from baseline in thyroid stimulating hormone (TSH)
Outcome Description
ECGs assess heart problems by measuring the electrical activity generated by the heart as it contracts. The components that will be assessed during the ECG are P wave, QRS complex, ST segment, and T wave.
Outcome Time Frame
Screening to date of confirmed disease progression, assessed up to 24 months
Outcome Measure
Changes from baseline in electrocardiograms (ECGs)
Outcome Description
ECOG performance status describes the level of impact that disease has on the patient's daily living abilities. Scale ranges from 0 (Fully active and able to carry on all pre-disease performance without restriction) to 5 (Dead).
Outcome Time Frame
Screening to date of confirmed disease progression, assessed up to 24 months
Outcome Measure
Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance
Outcome Description
IPI-549 blood concentrations in ng/mL.
Outcome Time Frame
Pre-dose, 0.5, 1.5, 3 and 6 hours following administration on Day 1 of Cycles 1 and 2 (each cycle is 28 days)
Outcome Measure
Population Pharmacokinetics (PK) of IPI-549-01
Outcome Description
Nivolumab blood concentrations will be assayed in ug/mL.
Outcome Time Frame
Pre-infusion and within 2 minutes of end of infusion on Day 1 of Cycles 1 and 4; Pre-infusion on Day 1 of Cycles 2 and 3, and every 4 cycles starting at Cycle 5 (each cycle is 28 days)
Outcome Measure
Pharmacokinetics (PK) of Nivolumab
Outcome Description
Pulse rate as measured in beats per minute (bpm)
Outcome Time Frame
Screening to date of confirmed disease progression, assessed up to 24 months
Outcome Measure
Changes from baseline in pulse rate
Outcome Description
Temperature as measured in celsius.
Outcome Time Frame
Screening to date of confirmed disease progression, assessed up to 24 months
Outcome Measure
Changes from baseline in temperature
Outcome Description
Respiration rate as measured in breaths per minute.
Outcome Time Frame
Screening to date of confirmed disease progression, assessed up to 24 months
Outcome Measure
Changes from baseline in respiration rate
Outcome Description
Systolic and diastolic blood pressure as measured in mmHg.
Outcome Time Frame
Screening to date of confirmed disease progression, assessed up to 24 months
Outcome Measure
Changes from baseline in blood pressure
See Also Links
Url
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404