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

Bladder Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03980041
• Other study ID #: IPI-549-02
• Status: Completed
• Phase: Phase 2
• Start date: September 25, 2019
• Est. completion date: November 15, 2022

Study information

• Verified date: November 2022
• Source: Infinity Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: November 15, 2022
• Est. primary completion date: November 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Cancer
• Bladder Cancer
• Carcinoma
• Carcinoma, Transitional Cell
• Solid Tumor
• Urothelial Carcinoma

Intervention

Drug:
• IPI-549 (eganelisib)
IPI-549 (40mg QD) administered orally in 28-day cycles
• Nivolumab
Nivolumab (480mg Q4W) administered intravenously (IV) in 28-day cycles
• Placebos
Placebo administered orally in 28-day cycles

Locations

Country	Name	City	State
Czechia	Onkologicka Klinika	Praha
France	Centre Oscar Lambret	Lille
France	Institut Paoli-Calmettes	Marseille
France	Centre Antoine Lacassagne	Nice
France	CHU de Strasbourg	Strasbourg
France	Institut Claudius Regaud	Toulouse
Italy	Istituto per la Ricerca e la Cura del Cancro (IRCC)	Candiolo
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola
Italy	Istituto Nazionale dei Tumori	Napoli
Poland	Oddzial Chorob Rozrostowych Wojewodzki Szpital	Lódz
Poland	Dzienny Oddzial Chemioterapii	Racibórz
Poland	EXAMEN sp	Skorzewo
Serbia	Clinical Centre of Serbia	Belgrade
Serbia	Institute for Oncology of Vojvodina	Sremska Kamenica
Spain	Hospital de Sant Creu i Sant Pau	Barcelona
Spain	ICO Institute Catalan of Oncology	Barcelona
Spain	IMQ Zorrotzaurre	Bilbao
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitatio HM Sanchinarro	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hospital Universitario	Sevilla
United States	University of MD - Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	Karmanos Cancer Center	Detroit	Michigan
United States	Parkview Physicians	Fort Wayne	Indiana
United States	Bon Secours St. Francis Cancer Center	Greenville	South Carolina
United States	Sarah Cannon Tennessee Oncology	Nashville	Tennessee
United States	Coborn Cancer Center	Saint Cloud	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Infinity Pharmaceuticals, Inc.	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Czechia,  France,  Italy,  Poland,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	First dosing date to date of first objective response, assessed up to 24 months
Secondary	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.	Date of first objective response to date of confirmed disease progression, assessed up to 24 months
Secondary	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.	First dosing to date to confirmed disease progression or death, assessed up to 48 months
Secondary	Changes from baseline in thyroid stimulating hormone (TSH)	If TSH result is abnormal, subsequent testing of Free T3 and free T4 required.	Pre-treatment (within 7 days of first dose) to date of confirmed disease progression, assessed up to 24 months
Secondary	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.	Screening to date of confirmed disease progression, assessed up to 24 months
Secondary	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).	Screening to date of confirmed disease progression, assessed up to 24 months
Secondary	Population Pharmacokinetics (PK) of IPI-549-01	IPI-549 blood concentrations in ng/mL.	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)
Secondary	Pharmacokinetics (PK) of Nivolumab	Nivolumab blood concentrations will be assayed in ug/mL.	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)
Secondary	Changes from baseline in pulse rate	Pulse rate as measured in beats per minute (bpm)	Screening to date of confirmed disease progression, assessed up to 24 months
Secondary	Changes from baseline in temperature	Temperature as measured in celsius.	Screening to date of confirmed disease progression, assessed up to 24 months
Secondary	Changes from baseline in respiration rate	Respiration rate as measured in breaths per minute.	Screening to date of confirmed disease progression, assessed up to 24 months
Secondary	Changes from baseline in blood pressure	Systolic and diastolic blood pressure as measured in mmHg.	Screening to date of confirmed disease progression, assessed up to 24 months

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