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, Adva

Condition: Bladder Cancer, Urothelial Carcinoma, Solid Tumor, Advanced Cancer

Intervention:

• Drug: IPI-549
• Drug: Nivolumab
• Drug: Placebos

Purpose: 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03980041

Sponsor: Infinity Pharmaceuticals, Inc.

Primary Outcome Measures:

• Measure: Objective Response Rate (ORR) per RECISTv1.1
• Time Frame: First dosing date to date of confirmed disease progression, assessed up to 24 months
• Safety Issue:

Secondary Outcome Measures:

• Measure: Time to Response (TTR)
• Time Frame: First dosing date to date of first objective response, assessed up to 24 months
• Safety Issue:
• Measure: Duration of Response (DOR)
• Time Frame: Date of first objective response to date of confirmed disease progression, assessed up to 24 months
• Safety Issue:
• Measure: Progression-Free Survival (PFS)
• Time Frame: First dosing to date to confirmed disease progression or death, assessed up to 48 months
• Safety Issue:
• Measure: Changes from baseline in thyroid stimulating hormone (TSH)
• Time Frame: Pre-treatment (within 7 days of first dose) to date of confirmed disease progression, assessed up to 24 months
• Safety Issue:
• Measure: Changes from baseline in electrocardiograms (ECGs)
• Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months
• Safety Issue:
• Measure: Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance
• Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months
• Safety Issue:
• Measure: Population Pharmacokinetics (PK) of IPI-549-01
• 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)
• Safety Issue:
• Measure: Pharmacokinetics (PK) of Nivolumab
• 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)
• Safety Issue:
• Measure: Changes from baseline in pulse rate
• Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months
• Safety Issue:
• Measure: Changes from baseline in temperature
• Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months
• Safety Issue:
• Measure: Changes from baseline in respiration rate
• Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months
• Safety Issue:
• Measure: Changes from baseline in blood pressure
• Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months
• Safety Issue:

Estimated Enrollment: 160

Study Start Date: September 25, 2019

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

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

Contact:

• Miriam Brody, MPH
• Miriam.Brody@infi.com
• 617-453-1142

Locations:

• Parkview Physicians
• Fort Wayne Indiana 46845 United States

• Karmanos Cancer Center
• Detroit Michigan 48201 United States

• Coborn Cancer Center
• Saint Cloud Minnesota 56303 United States

• Bon Secours St. Francis Cancer Center
• Greenville South Carolina 29607 United States

• Onkologicka Klinika
• Praha 140 59 Czechia

• Dzienny Oddzial Chemioterapii
• Racibórz Poland

• EXAMEN sp
• Skorzewo 60-185 Poland

• Oddzial Chorob Rozrostowych Wojewodzki Szpital
• Łódź 90-242 Poland

• Hospital de Sant Creu i Sant Pau
• Barcelona 8041 Spain

• Hospital Ramon y Cajal
• Madrid 28034 Spain

• Hospital Universitatio HM Sanchinarro
• Madrid 28050 Spain

• Hospital Universitario
• Sevilla 41013 Spain

View trial on ClinicalTrials.gov