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

Brief Title

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

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.

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Objective Response Rate (ORR) per RECISTv1.1

Secondary Outcome

 Time to Response (TTR)

Condition

Bladder Cancer

Intervention

IPI-549 (eganelisib)

Study Arms / Comparison Groups

 IPI-549 + Nivolumab

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

September 25, 2019

Completion Date

November 15, 2022

Primary Completion Date

November 30, 2020

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

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Halle Zhang, PhD, RN, ,

Location Countries

Czechia

Location Countries

Czechia

Administrative Informations

NCT ID

NCT03980041

Organization ID

IPI-549-02

Responsible Party

Sponsor

Study Sponsor

Infinity Pharmaceuticals, Inc.

Collaborators

 Bristol-Myers Squibb

Study Sponsor

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

Verification Date

November 2022