Back to resultsStudy to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)
Primary Purpose
Bladder Cancer, Urothelial Carcinoma, Solid Tumor
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IPI-549 (eganelisib)
Nivolumab
Placebos
Sponsored by
About this trial
This is an interventional treatment trial for Bladder Cancer focused on measuring eganelisib, IPI-549
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
Sites / Locations
- Parkview Physicians
- University of MD - Greenebaum Comprehensive Cancer Center
- Karmanos Cancer Center
- Coborn Cancer Center
- Montefiore Medical Center
- Bon Secours St. Francis Cancer Center
- Sarah Cannon Tennessee Oncology
- Onkologicka Klinika
- Centre Oscar Lambret
- Institut Paoli-Calmettes
- Centre Antoine Lacassagne
- CHU de Strasbourg
- Institut Claudius Regaud
- Istituto per la Ricerca e la Cura del Cancro (IRCC)
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
- Istituto Nazionale dei Tumori
- Dzienny Oddzial Chemioterapii
- EXAMEN sp
- Oddzial Chorob Rozrostowych Wojewodzki Szpital
- Clinical Centre of Serbia
- Institute for Oncology of Vojvodina
- ICO Institute Catalan of Oncology
- Hospital de Sant Creu i Sant Pau
- IMQ Zorrotzaurre
- MD Anderson Cancer Center Madrid
- Hospital Ramón y Cajal
- Hospital Universitatio HM Sanchinarro
- Hospital Universitario Central de Asturias
- Hospital Universitario
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
IPI-549 + Nivolumab
Placebo + Nivolumab
Arm Description
Participants receive IPI-549 orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
Participants receive placebo orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR) per RECISTv1.1
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.
Secondary Outcome Measures
Time to Response (TTR)
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.
Duration of Response (DOR)
DOR is defined as the time from the first objective response (CR or PR) to documented disease progression in patients with CR or PR.
Progression-Free Survival (PFS)
PFS is defined as the time from the first dose of study treatment to documented disease progression or death due to any cause.
Changes from baseline in thyroid stimulating hormone (TSH)
If TSH result is abnormal, subsequent testing of Free T3 and free T4 required.
Changes from baseline in electrocardiograms (ECGs)
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.
Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance
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).
Population Pharmacokinetics (PK) of IPI-549-01
IPI-549 blood concentrations in ng/mL.
Pharmacokinetics (PK) of Nivolumab
Nivolumab blood concentrations will be assayed in ug/mL.
Changes from baseline in pulse rate
Pulse rate as measured in beats per minute (bpm)
Changes from baseline in temperature
Temperature as measured in celsius.
Changes from baseline in respiration rate
Respiration rate as measured in breaths per minute.
Changes from baseline in blood pressure
Systolic and diastolic blood pressure as measured in mmHg.
Full Information
NCT ID
NCT03980041
First Posted
April 22, 2019
Last Updated
November 22, 2022
Sponsor
Infinity Pharmaceuticals, Inc.
Collaborators
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT03980041
Brief Title
Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
September 25, 2019 (Actual)
Primary Completion Date
November 30, 2020 (Actual)
Study Completion Date
November 15, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Infinity Pharmaceuticals, Inc.
Collaborators
Bristol-Myers Squibb
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer, Urothelial Carcinoma, Solid Tumor, Advanced Cancer
Keywords
eganelisib, IPI-549
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IPI-549 + Nivolumab
Arm Type
Experimental
Arm Description
Participants receive IPI-549 orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
Arm Title
Placebo + Nivolumab
Arm Type
Active Comparator
Arm Description
Participants receive placebo orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
Intervention Type
Drug
Intervention Name(s)
IPI-549 (eganelisib)
Other Intervention Name(s)
IPI549
Intervention Description
IPI-549 (40mg QD) administered orally in 28-day cycles
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
OPDIVO®
Intervention Description
Nivolumab (480mg Q4W) administered intravenously (IV) in 28-day cycles
Intervention Type
Drug
Intervention Name(s)
Placebos
Other Intervention Name(s)
Placebo
Intervention Description
Placebo administered orally in 28-day cycles
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) per RECISTv1.1
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.
Time Frame
First dosing date to date of confirmed disease progression, assessed up to 24 months
Secondary Outcome Measure Information:
Title
Time to Response (TTR)
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.
Time Frame
First dosing date to date of first objective response, assessed up to 24 months
Title
Duration of Response (DOR)
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.
Time Frame
Date of first objective response to date of confirmed disease progression, assessed up to 24 months
Title
Progression-Free Survival (PFS)
Description
PFS is defined as the time from the first dose of study treatment to documented disease progression or death due to any cause.
Time Frame
First dosing to date to confirmed disease progression or death, assessed up to 48 months
Title
Changes from baseline in thyroid stimulating hormone (TSH)
Description
If TSH result is abnormal, subsequent testing of Free T3 and free T4 required.
Time Frame
Pre-treatment (within 7 days of first dose) to date of confirmed disease progression, assessed up to 24 months
Title
Changes from baseline in electrocardiograms (ECGs)
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.
Time Frame
Screening to date of confirmed disease progression, assessed up to 24 months
Title
Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance
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).
Time Frame
Screening to date of confirmed disease progression, assessed up to 24 months
Title
Population Pharmacokinetics (PK) of IPI-549-01
Description
IPI-549 blood concentrations in ng/mL.
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)
Title
Pharmacokinetics (PK) of Nivolumab
Description
Nivolumab blood concentrations will be assayed in ug/mL.
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)
Title
Changes from baseline in pulse rate
Description
Pulse rate as measured in beats per minute (bpm)
Time Frame
Screening to date of confirmed disease progression, assessed up to 24 months
Title
Changes from baseline in temperature
Description
Temperature as measured in celsius.
Time Frame
Screening to date of confirmed disease progression, assessed up to 24 months
Title
Changes from baseline in respiration rate
Description
Respiration rate as measured in breaths per minute.
Time Frame
Screening to date of confirmed disease progression, assessed up to 24 months
Title
Changes from baseline in blood pressure
Description
Systolic and diastolic blood pressure as measured in mmHg.
Time Frame
Screening to date of confirmed disease progression, assessed up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Halle Zhang, PhD, RN
Organizational Affiliation
Infinity Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Parkview Physicians
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46845
Country
United States
Facility Name
University of MD - Greenebaum Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Karmanos Cancer Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Coborn Cancer Center
City
Saint Cloud
State/Province
Minnesota
ZIP/Postal Code
56303
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Bon Secours St. Francis Cancer Center
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29607
Country
United States
Facility Name
Sarah Cannon Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Onkologicka Klinika
City
Praha
ZIP/Postal Code
140 59
Country
Czechia
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
Institut Paoli-Calmettes
City
Marseille
ZIP/Postal Code
13009
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
ZIP/Postal Code
06189
Country
France
Facility Name
CHU de Strasbourg
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Facility Name
Institut Claudius Regaud
City
Toulouse
ZIP/Postal Code
31300
Country
France
Facility Name
Istituto per la Ricerca e la Cura del Cancro (IRCC)
City
Candiolo
ZIP/Postal Code
10060
Country
Italy
Facility Name
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
City
Meldola
ZIP/Postal Code
47104
Country
Italy
Facility Name
Istituto Nazionale dei Tumori
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Dzienny Oddzial Chemioterapii
City
Racibórz
ZIP/Postal Code
47-400
Country
Poland
Facility Name
EXAMEN sp
City
Skorzewo
ZIP/Postal Code
60-185
Country
Poland
Facility Name
Oddzial Chorob Rozrostowych Wojewodzki Szpital
City
Łódź
ZIP/Postal Code
93-153
Country
Poland
Facility Name
Clinical Centre of Serbia
City
Belgrade
ZIP/Postal Code
11 000
Country
Serbia
Facility Name
Institute for Oncology of Vojvodina
City
Sremska Kamenica
ZIP/Postal Code
21 204
Country
Serbia
Facility Name
ICO Institute Catalan of Oncology
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital de Sant Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
8005
Country
Spain
Facility Name
IMQ Zorrotzaurre
City
Bilbao
ZIP/Postal Code
48180
Country
Spain
Facility Name
MD Anderson Cancer Center Madrid
City
Madrid
ZIP/Postal Code
28033
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Universitatio HM Sanchinarro
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Universitario Central de Asturias
City
Oviedo
ZIP/Postal Code
33011
Country
Spain
Facility Name
Hospital Universitario
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.infi.com/home/our-development-program/ipi-549/
Description
Related Info
Learn more about this trial
Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)
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