Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)

NCT03980041 | Completed Phase 2 FDA Drug

• 1 other identifier: IPI-549-02
• Study Type: interventional
• Target: 49
• Locations: 7 countries
• Sites: 29

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.

Conditions

Bladder Cancer; Urothelial Carcinoma; Solid Tumor; Advanced Cancer

Keywords

eganelisib; IPI-549

Outcome Measures

Primary Outcomes (1)

• 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.

  First dosing date to date of confirmed disease progression, assessed up to 24 months

Secondary Outcomes (12)

• Time to Response (TTR)

  First dosing date to date of first objective response, assessed up to 24 months

• Duration of Response (DOR)

  Date of first objective response to date of confirmed disease progression, assessed up to 24 months

• Progression-Free Survival (PFS)

  First dosing to date to confirmed disease progression or death, assessed up to 48 months

• Changes from baseline in thyroid stimulating hormone (TSH)

  Pre-treatment (within 7 days of first dose) to date of confirmed disease progression, assessed up to 24 months

• Changes from baseline in electrocardiograms (ECGs)

  Screening to date of confirmed disease progression, assessed up to 24 months

Study Arms (2)

IPI-549 + Nivolumab

EXPERIMENTAL

Participants receive IPI-549 orally (PO) daily in combination with nivolumab IV infusion every 4 weeks

Drug: IPI-549 (eganelisib); Drug: Nivolumab

Placebo + Nivolumab

ACTIVE COMPARATOR

Participants receive placebo orally (PO) daily in combination with nivolumab IV infusion every 4 weeks

Drug: Nivolumab; Drug: Placebos

Interventions

IPI-549 (eganelisib) DRUG

IPI-549 (40mg QD) administered orally in 28-day cycles

Also known as: IPI549

IPI-549 + Nivolumab

Nivolumab DRUG

Nivolumab (480mg Q4W) administered intravenously (IV) in 28-day cycles

Also known as: OPDIVO®

IPI-549 + Nivolumab; Placebo + Nivolumab

Placebos DRUG

Placebo administered orally in 28-day cycles

Also known as: Placebo

Placebo + Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Infinity Pharmaceuticals, Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (29)

Parkview Physicians

Fort Wayne, Indiana, 46845, United States

Location

University of MD - Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Coborn Cancer Center

Saint Cloud, Minnesota, 56303, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Bon Secours St. Francis Cancer Center

Greenville, South Carolina, 29607, United States

Location

Sarah Cannon Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Onkologicka Klinika

Prague, 140 59, Czechia

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Institut Paoli-Calmettes

Marseille, 13009, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

CHU de Strasbourg

Strasbourg, 67000, France

Location

Institut Claudius Regaud

Toulouse, 31300, France

Location

Istituto per la Ricerca e la Cura del Cancro (IRCC)

Candiolo, 10060, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47104, Italy

Location

Istituto Nazionale dei Tumori

Napoli, 80131, Italy

Location

Oddzial Chorob Rozrostowych Wojewodzki Szpital

Lodz, 93-153, Poland

Location

Dzienny Oddzial Chemioterapii

Racibórz, 47-400, Poland

Location

EXAMEN sp

Skorzewo, 60-185, Poland

Location

Clinical Centre of Serbia

Belgrade, 11 000, Serbia

Location

Institute for Oncology of Vojvodina

Kamenitz, 21 204, Serbia

Location

ICO Institute Catalan of Oncology

Barcelona, 08907, Spain

Location

Hospital de Sant Creu i Sant Pau

Barcelona, 8005, Spain

Location

IMQ Zorrotzaurre

Bilbao, 48180, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, 28033, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitatio HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

Location

Hospital Universitario

Seville, 41013, Spain

Location

Related Links

• Related Info

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

IPI-549; Nivolumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Halle Zhang, PhD, RN

  Infinity Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2019
• First Posted: June 10, 2019
• Study Start: September 25, 2019
• Primary Completion: November 30, 2020
• Study Completion: November 15, 2022
• Last Updated: November 25, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3); SE (2); FR (5); ES (8); PL (3); CZ (1); US (7)