Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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

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

IPI-549 (40mg QD) administered orally in 28-day cycles

IPI-549 (eganelisib)

Nivolumab (480mg Q4W) administered intravenously (IV) in 28-day cycles

Placebo administered orally in 28-day cycles

Placebos

Halle Zhang, PhD, RN

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

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

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.

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.

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

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

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

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.

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).

Nivolumab blood concentrations will be assayed in ug/mL.

Pulse rate as measured in beats per minute (bpm)

Respiration rate as measured in breaths per minute.

Systolic and diastolic blood pressure as measured in mmHg.

Bristol-Myers Squibb

Infinity Pharmaceuticals, Inc.

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Carcinoma, Renal Cell

Breast Diseases

Skin Diseases

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Paclitaxel

Albumin-Bound Paclitaxel

Bevacizumab

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Endothelial Growth Factors

Mitogens

Antimitotic Agents

Tubulin Modulators

Angiogenesis Inhibitors

Growth Inhibitors

IPI-549 in combination with front-line treatment. Cohort A will include two sub-cohorts: Cohorts A1 and A2.

Cohort A1: Approximately 30 patients with locally advanced and/or metastatic TNBC with programmed death-ligand 1 (PDL1) positive disease based on immunohistochemistry (IHC) defined as IC1/2/3.

Cohort A2: Approximately 30 patients with locally advanced and/or metastatic TNBC with PDL1 negative disease based on IHC defined as IC0.

IPI-549 in combination with front-line treatment. Cohort B will include two sub-cohorts: Cohorts B1 and B2.

Cohort B1: Approximately 15 patients with locally advanced and/or metastatic RCC, with PDL1 positive disease based on IHC defined as IC1/2/3.

Cohort B2: Approximately 15 patients with locally advanced and/or metastatic RCC, with PDL1 negative disease based on IHC defined as IC0.

IPI-549 is an oral, selective inhibitor of phosphoinositide-3-kinase gamma (PI3K-gamma). It is an orally-administered capsule that will be dosed at either 20mg/day, 30mg/day, or 40mg/day to patients in both cohorts A and B depending on the results of the safety run-in phase for each cohort.

Atezolizumab is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1). 840 mg of the drug will be administered intravenously (IV) on days 1 and 15 in combination of each 28-day cycle for patients with TNBC. 1200mg will be administered IV on day 1 of each 21-day cycle to patients with RCC.

Nab-paclitaxel is a nanoparticle albumin-bound formulation of paclitaxel (Taxol), a mitotic inhibitor chemotherapy, with less toxicity than solvent-based (sb) paclitaxel and achieves a 33% higher tumor uptake in preclinical models. Nab-paclitaxel will be administered intravenously (IV) at 100 mg/m2 on days 1, 8 and 15 of each 28-day cycle for patients with TNBC.

nab-paclitaxel

Bevacizumab is an anti-vascular endothelial growth factor (anti-VEGF) recombinant monoclonal antibody that is approved by the FDA for the treatment of multiple solid tumors in combination with chemotherapy. It will be administered at 15 mg/kg IV on day 1 of each 21-day cycle to patients with RCC.

Feng Chi, PhD, RN

MARIO-3 is a Phase 2 multi-arm combination cohort study designed to evaluate IPI-549, Infinity Pharmaceutical's first-in-class, oral immuno-oncology product candidate targeting immune-suppressive tumor-associated myeloid cells through selective inhibition of phosphoinositide-3-kinase (PI3K)-gamma, in combinations with Tecentriq and Abraxane (nab-paclitaxel) in front-line triple negative breast cancer (TNBC) and in combination with Tecentriq and Avastin (bevacizumab) in front-line renal cell cancer (RCC).

MARIO-3 (Macrophage Reprogramming in Immuno-Oncology) is a prospective Phase 2 multi-arm, multicenter, open-label, combination cohort study designed to evaluate IPI-549, Infinity Pharmaceutical's first-in-class, oral immuno-oncology product candidate targeting immune-suppressive tumor-associated myeloid cells through selective inhibition of phosphoinositide-3-kinase (PI3K)-gamma. IPI-549 will be administered in combinations with Tecentriq and Abraxane (nab-paclitaxel) in front-line triple negative breast cancer (TNBC) and in combination with Tecentriq and Avastin (bevacizumab) in front-line renal cell cancer (RCC).

This study will enroll approximately 90 treatment-naïve patients across the following disease cohorts. Cohort A will be composed of patients with locally advanced and/or metastatic triple-negative breast cancer (TNBC). Cohort B will be composed of patients with locally advanced and/or metastatic renal cell carcinoma (RCC).

The primary objective of MARIO-3 is to evaluate the complete response (CR) rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 following combination treatment with IPI-549 and front-line treatment in patients with TNBC and RCC. Its secondary objectives include evaluation of the safety, objective response rate (ORR), time to CR (TTCR), time to response (TTR), duration of CR (DOCR), duration of response (DOR), and progression-free survival (PFS).

Participants are assigned to one of two or more groups in parallel for the duration of the study.

Evaluation of IPI-549 Combined With Front-line Treatments in Pts. With Triple-Negative Breast Cancer or Renal Cell Carcinoma

Ph 2, Multi-arm, Multicenter, Open-label Study to Evaluate Efficacy and Safety of IPI-549 Administered in Combo With Front-line Treatment Regimens in Pts With Locally Advanced and/or Metastatic Triple-Negative Breast Cancer or Renal Cell Carcinoma

Complete Response (CR) rate is defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as disappearance of all target and non-target lesions.

Treatment emergent adverse events (TEAE) are undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment.

Serious adverse events include death, life-threatening events, initial or prolonged hospitalization, disability or permanent damage, or require an intervention to prevent impairment.

An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

ORR is defined as best response of CR or partial response (PR), as determined by RECIST v1.1.

TTCR is defined as the time from the first dose of study treatment to CR.

TTR is defined as the time from the first dose of study treatment to first objective response (CR or PR) in patients with CR or PR.

DOCR is defined as the time from the first CR to documented disease progression in patients with CR.

Population PK estimates (variability in drug concentrations within the study population measured in ng/mL) includes inter- and intra-subject variability and covariate effects.

Concentration of Atezolizumab in the blood at predose measured in ug/mL.

Pulse rate as measured in beats per minute (bpm).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)	NCT03980041	Bladder Cancer Urothelial Carc... Solid Tumor Advanced Cancer	IPI-549 (eganel... Nivolumab Placebos	18 Years -	Infinity Pharmaceuticals, Inc.
Evaluation of IPI-549 Combined With Front-line Treatments in Pts. With Triple-Negative Breast Cancer or Renal Cell Carcinoma	NCT03961698	Breast Cancer Renal Cell Carc...	IPI-549 (eganel... Atezolizumab nab-paclitaxel Bevacizumab	18 Years -	Infinity Pharmaceuticals, Inc.

Spots Global Cancer Trial Database for eganelisib

Every month we try and update this database with for eganelisib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for eganelisib

Every month we try and update this database with for eganelisib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for eganelisib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.