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

Sponsor
Infinity Pharmaceuticals, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03980041
Collaborator
Bristol-Myers Squibb (Industry)
160
Enrollment
29
Locations
2
Arms
38.2
Anticipated Duration (Months)
5.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
160 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 25, 2019
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: IPI-549 + Nivolumab

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

Drug: IPI-549 (eganelisib)
IPI-549 (40mg QD) administered orally in 28-day cycles
Other Names:
  • IPI549

    • Drug: Nivolumab
    Nivolumab (480mg Q4W) administered intravenously (IV) in 28-day cycles
    Other Names:
  • OPDIVO®

    		•
    Active Comparator: Placebo + Nivolumab

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

    Drug: Nivolumab
    Nivolumab (480mg Q4W) administered intravenously (IV) in 28-day cycles
    Other Names:
  • OPDIVO®

    • Drug: Placebos
    Placebo administered orally in 28-day cycles
    Other Names:
  • Placebo

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate (ORR) per RECISTv1.1 [First dosing date to date of confirmed disease progression, assessed up to 24 months]

      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

    1. Time to Response (TTR) [First dosing date to date of first objective response, assessed up to 24 months]

      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.

    2. Duration of Response (DOR) [Date of first objective response to date of confirmed disease progression, assessed up to 24 months]

      DOR is defined as the time from the first objective response (CR or PR) to documented disease progression in patients with CR or PR.

    3. Progression-Free Survival (PFS) [First dosing to date to confirmed disease progression or death, assessed up to 48 months]

      PFS is defined as the time from the first dose of study treatment to documented disease progression or death due to any cause.

    4. 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]

      If TSH result is abnormal, subsequent testing of Free T3 and free T4 required.

    5. Changes from baseline in electrocardiograms (ECGs) [Screening to date of confirmed disease progression, assessed up to 24 months]

      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.

    6. Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance [Screening to date of confirmed disease progression, assessed up to 24 months]

      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).

    7. Population Pharmacokinetics (PK) of IPI-549-01 [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)]

      IPI-549 blood concentrations in ng/mL.

    8. Pharmacokinetics (PK) of Nivolumab [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)]

      Nivolumab blood concentrations will be assayed in ug/mL.

    9. Changes from baseline in pulse rate [Screening to date of confirmed disease progression, assessed up to 24 months]

      Pulse rate as measured in beats per minute (bpm)

    10. Changes from baseline in temperature [Screening to date of confirmed disease progression, assessed up to 24 months]

      Temperature as measured in celsius.

    11. Changes from baseline in respiration rate [Screening to date of confirmed disease progression, assessed up to 24 months]

      Respiration rate as measured in breaths per minute.

    12. Changes from baseline in blood pressure [Screening to date of confirmed disease progression, assessed up to 24 months]

      Systolic and diastolic blood pressure as measured in mmHg.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

      1. With at least 1 platinum-based chemotherapy regimen for the treatment of metastatic (Stage IV) or locally advanced unresectable disease; or
      1. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Parkview Physicians Fort Wayne Indiana United States 46845
    2 University of MD - Greenebaum Comprehensive Cancer Center Baltimore Maryland United States 21201
    3 Karmanos Cancer Center Detroit Michigan United States 48201
    4 Coborn Cancer Center Saint Cloud Minnesota United States 56303
    5 Montefiore Medical Center Bronx New York United States 10461
    6 Bon Secours St. Francis Cancer Center Greenville South Carolina United States 29607
    7 Sarah Cannon Tennessee Oncology Nashville Tennessee United States 37203
    8 Onkologicka Klinika Praha Czechia 140 59
    9 Centre Oscar Lambret Lille France 59020
    10 Institut Paoli-Calmettes Marseille France 13009
    11 Centre Antoine Lacassagne Nice France 06189
    12 CHU de Strasbourg Strasbourg France 67000
    13 Institut Claudius Regaud Toulouse France 31300
    14 Istituto per la Ricerca e la Cura del Cancro (IRCC) Candiolo Italy 10060
    15 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Meldola Italy 47104
    16 Istituto Nazionale dei Tumori Napoli Italy 80131
    17 Dzienny Oddzial Chemioterapii Racibórz Poland 47-400
    18 EXAMEN sp Skorzewo Poland 60-185
    19 Oddzial Chorob Rozrostowych Wojewodzki Szpital Łódź Poland 93-153
    20 Clinical Centre of Serbia Belgrade Serbia 11 000
    21 Institute for Oncology of Vojvodina Sremska Kamenica Serbia 21 204
    22 ICO Institute Catalan of Oncology Barcelona Spain 08907
    23 Hospital de Sant Creu i Sant Pau Barcelona Spain 8005
    24 IMQ Zorrotzaurre Bilbao Spain 48180
    25 MD Anderson Cancer Center Madrid Madrid Spain 28033
    26 Hospital Ramón y Cajal Madrid Spain 28034
    27 Hospital Universitatio HM Sanchinarro Madrid Spain 28050
    28 Hospital Universitario Central de Asturias Oviedo Spain 33011
    29 Hospital Universitario Sevilla Spain 41013

    Sponsors and Collaborators

    • Infinity Pharmaceuticals, Inc.
    • Bristol-Myers Squibb

    Investigators

    • Study Director: Halle Zhang, PhD, RN, Infinity Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Infinity Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT03980041
    Other Study ID Numbers:
    • IPI-549-02
    First Posted:
    Jun 10, 2019
    Last Update Posted:
    Apr 4, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Infinity Pharmaceuticals, Inc.
    eganelisib
    IPI-549
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Transitional Cell
    Nivolumab

    Study Results

    No Results Posted as of Apr 4, 2022