Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)
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|ClinicalTrials.gov Identifier: NCT03980041|
Recruitment Status : Completed
First Posted : June 10, 2019
Last Update Posted : November 25, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer Urothelial Carcinoma Solid Tumor Advanced Cancer||Drug: IPI-549 (eganelisib) Drug: Nivolumab Drug: Placebos||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||49 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|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 :||September 25, 2019|
|Actual Primary Completion Date :||November 30, 2020|
|Actual Study Completion Date :||November 15, 2022|
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 Name: IPI549
Nivolumab (480mg Q4W) administered intravenously (IV) in 28-day cycles
Other Name: OPDIVO®
Active Comparator: Placebo + Nivolumab
Participants receive placebo orally (PO) daily in combination with nivolumab IV infusion every 4 weeks
Nivolumab (480mg Q4W) administered intravenously (IV) in 28-day cycles
Other Name: OPDIVO®
Placebo administered orally in 28-day cycles
Other Name: Placebo
- Objective Response Rate (ORR) per RECISTv1.1 [ Time Frame: 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.
- Time to Response (TTR) [ Time Frame: 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.
- Duration of Response (DOR) [ Time Frame: 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.
- Progression-Free Survival (PFS) [ Time Frame: 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.
- 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 ]If TSH result is abnormal, subsequent testing of Free T3 and free T4 required.
- Changes from baseline in electrocardiograms (ECGs) [ Time Frame: 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.
- Changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance [ Time Frame: 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).
- 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) ]IPI-549 blood concentrations in ng/mL.
- 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) ]Nivolumab blood concentrations will be assayed in ug/mL.
- Changes from baseline in pulse rate [ Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months ]Pulse rate as measured in beats per minute (bpm)
- Changes from baseline in temperature [ Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months ]Temperature as measured in celsius.
- Changes from baseline in respiration rate [ Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months ]Respiration rate as measured in breaths per minute.
- Changes from baseline in blood pressure [ Time Frame: Screening to date of confirmed disease progression, assessed up to 24 months ]Systolic and diastolic blood pressure as measured in mmHg.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03980041
|Study Director:||Halle Zhang, PhD, RN||Infinity Pharmaceuticals, Inc.|
|Responsible Party:||Infinity Pharmaceuticals, Inc.|
|Other Study ID Numbers:||
|First Posted:||June 10, 2019 Key Record Dates|
|Last Update Posted:||November 25, 2022|
|Last Verified:||November 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action