Clinical trial NCT03980041: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Urothelial Carcinoma
Solid Tumor
Advanced Cancer
Keywords: eganelisib
IPI-549
Lead sponsor: Infinity Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2019-06-10
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate (ORR) per RECISTv1.1
timeFrame: First dosing date to date of confirmed disease progression, assessed up to 24 months
Secondary outcomes:
measure: Time to Response (TTR)
timeFrame: First dosing date to date of first objective response, assessed up to 24 months
measure: Duration of Response (DOR)
timeFrame: Date of first objective response to date of confirmed disease progression, assessed up to 24 months
measure: Progression-Free Survival (PFS)
timeFrame: First dosing to date to confirmed disease progression or death, assessed up to 48 months
measure: Changes from baseline in thyroid stimulating hormone (TSH)
timeFrame: Pre-treatment (within 7 days of first dose) to date of confirmed disease progression, assessed up to 24 months
measure: Changes from baseline in electrocardiograms (ECGs)
timeFrame: Screening to date of confirmed disease progression, assessed up to 24 months
measure: Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance
timeFrame: Screening to date of confirmed disease progression, assessed up to 24 months
measure: Population Pharmacokinetics (PK) of IPI-549-01
timeFrame: 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)
measure: Pharmacokinetics (PK) of Nivolumab
timeFrame: 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)
measure: Changes from baseline in pulse rate
timeFrame: Screening to date of confirmed disease progression, assessed up to 24 months
measure: Changes from baseline in temperature
timeFrame: Screening to date of confirmed disease progression, assessed up to 24 months
measure: Changes from baseline in respiration rate
timeFrame: Screening to date of confirmed disease progression, assessed up to 24 months
measure: Changes from baseline in blood pressure
timeFrame: Screening to date of confirmed disease progression, assessed up to 24 months
Other outcomes:
Locations:
city: Fort Wayne
country: United States
facility: Parkview Physicians
state: Indiana
city: Baltimore
country: United States
facility: University of MD - Greenebaum Comprehensive Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Saint Cloud
country: United States
facility: Coborn Cancer Center
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Greenville
country: United States
facility: Bon Secours St. Francis Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Tennessee Oncology
state: Tennessee
city: Praha
country: Czechia
facility: Onkologicka Klinika
city: Lille
country: France
facility: Centre Oscar Lambret
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Candiolo
country: Italy
facility: Istituto per la Ricerca e la Cura del Cancro (IRCC)
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori
city: Racibórz
country: Poland
facility: Dzienny Oddzial Chemioterapii
city: Skorzewo
country: Poland
facility: EXAMEN sp
city: Łódź
country: Poland
facility: Oddzial Chorob Rozrostowych Wojewodzki Szpital
city: Belgrade
country: Serbia
facility: Clinical Centre of Serbia
city: Sremska Kamenica
country: Serbia
facility: Institute for Oncology of Vojvodina
city: Barcelona
country: Spain
facility: ICO Institute Catalan of Oncology
city: Barcelona
country: Spain
facility: Hospital de Sant Creu i Sant Pau
city: Bilbao
country: Spain
facility: IMQ Zorrotzaurre
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitatio HM Sanchinarro
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Sevilla
country: Spain
facility: Hospital Universitario
Study officials:
affiliation: Infinity Pharmaceuticals, Inc.
name: Halle Zhang, PhD, RN
role: STUDY_DIRECTOR
References: