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

NCT03961698 | Unknown Phase 2 FDA Drug

• 1 other identifier: IPI-549-03
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 24

Brief Summary

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).

Conditions

Breast Cancer; Renal Cell Carcinoma

Keywords

Phase 2; PI3K; IPI-549; Advanced Solid Tumor; Triple Negative Breast Cancer (TNBC); Renal Cell Carcinoma (RCC); PD-L1; Myeloid-Derived Suppressor Cells (MDSCs); Front-Line Treatment; eganelisib

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) rate (change in target lesion size).

  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.

  CR rate assessments will be conducted through month 12 for Cohort A (TNBC) and through month 18 for Cohort B (RCC) until unacceptable toxicity, confirmed progression of disease, withdrawal of consent, or other treatment discontinuation criteria are met.

Secondary Outcomes (16)

• Incidence of treatment-emergent adverse events (TEAEs)

  TEAE assessments will be conducted from screening through month 12 for Cohort A (TNBC) and from screening through month 18 for Cohort B (RCC). Additional assessments will be conducted 30 days and 90 days from last dose.

• Incidence of serious adverse events (SAEs), including deaths

  SAE assessments will be conducted from screening through month 12 for Cohort A (TNBC) and from screening through month 18 for Cohort B (RCC). Additional assessments will be conducted 30 days and 90 days from last dose.

• Incidence of adverse events (AEs) leading to treatment discontinuation

  AE assessments will be conducted from screening through month 12 for Cohort A (TNBC) and from screening through month 18 for Cohort B (RCC). Additional assessments will be conducted 30 days and 90 days from last dose.

• Changes from baseline in electrocardiograms (ECGs)

  ECG assessments will be performed from screening through month 12 for Cohort A (TNBC) and from screening through month 18 for Cohort B (RCC).

• Objective response rate (ORR)

  ORR will be assessed from screening through month 12 for Cohort A (TNBC) and from screening through month 18 for Cohort B (RCC).

Study Arms (2)

Cohort A (TNBC)

EXPERIMENTAL

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.

Drug: IPI-549 (eganelisib); Drug: Atezolizumab; Drug: nab-paclitaxel

Cohort B (RCC)

EXPERIMENTAL

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.

Drug: IPI-549 (eganelisib); Drug: Atezolizumab; Drug: Bevacizumab

Interventions

IPI-549 (eganelisib) DRUG

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.

Cohort A (TNBC); Cohort B (RCC)

Atezolizumab DRUG

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.

Also known as: Tecentriq

Cohort A (TNBC); Cohort B (RCC)

nab-paclitaxel DRUG

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.

Also known as: Abraxane

Cohort A (TNBC)

Bevacizumab DRUG

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.

Also known as: Avastin

Cohort B (RCC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age.
• Have signed and dated an independent review board (IRB)/independent ethics committee (IEC) approved informed consent form (ICF) in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
• Willing and able to comply with scheduled visits, treatment schedule, laboratory tests, fresh tumor biopsies, and all other protocol requirements.
• At least 1 measurable disease lesion by computed tomography (CT) or magnetic resonance imaging (MRI) as defined by RECIST v1.1 performed within 1 week prior to first dose.
• Willing to undergo one pre-treatment core biopsy (unless archival tumor tissue is available within 3 months of first dose) and one on-treatment tumor biopsy, unless not safe or medically feasible. If the patient is unwilling to undergo biopsy, they may be eligible with approval of the medical monitor.
• Evaluable tumor tissue (archived \[without time constraints\] or new biopsy) must be provided for biomarker analysis, which will include PD-L1 expression level using immunohistochemistry (IHC) to measure specific PD-L1 signals in tumor-infiltrating immune cells (ICs). Results are not required prior to start of study treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Life expectancy ≥12 weeks.
• Baseline laboratory values must meet the following criteria within 14 days of the first dose:
• Adequate hematologic function, defined as white blood cell (WBC) count ≥2.0 × 109/L, absolute neutrophil count ≥1.5 × 109/L (without granulocyte colony-stimulating factor \[GCSF\] support within 2 weeks prior to Cycle 1, Day 1), lymphocyte count ≥0.5 × 109/L, hemoglobin ≥9.0 g/dL (patients may be transfused or receive erythropoietic treatment to meet this criterion), and platelet count ≥100 × 109/L (without transfusion within 2 weeks prior to Cycle 1, Day 1).
• Calculated creatinine clearance ≥30 mL/min.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) \<2.5 × upper limit of normal (ULN). ALT and AST ≤5 × ULN if documented liver metastasis. ALP ≤5 × ULN if documented bone or liver metastasis.
• Total bilirubin ≤1.25 × ULN (unless elevated due to Gilbert's syndrome who can have total bilirubin \<3.0 mg/dL).
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN. This applies to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
• Serum albumin \>2.5 g/dL

You may not qualify if:

• WOCBP who are pregnant or breastfeeding.
• Women with a positive pregnancy test at enrollment or prior to administration of study medication.
• Any serious or uncontrolled medical disorder that, in the opinion of the Investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the patient to receive protocol therapy, or interfere with the interpretation of study results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
• Any history of, or currently active, brain or leptomeningeal metastases.
• Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina. Patients with a known left ventricular ejection fraction (LVEF) \<40% will be excluded. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF \<50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
• Baseline QT interval corrected with Fridericia's method (QTcF) \>480 ms.
• Major surgical procedure within 4 weeks prior to enrollment or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis. Placement of central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure and is therefore permitted.
• Active tuberculosis.
• Ongoing systemic bacterial, fungal, or viral infections at Screening.
• Positive test for human immunodeficiency virus (HIV).
• Active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
• Dependence on continuous supplemental oxygen use.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled hypercalcemia (\>1.5 mmol/L ionized calcium or calcium \>12 mg/dL or corrected serum calcium \>ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy. Patients who are receiving denosumab must discontinue denosumab use and replace it with a bisphosphonate instead while on study. There is no required minimum washout period for denosumab. Patients who are receiving bisphosphonate therapy specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells, or any of the study drug components.

Sponsors & Collaborators

• Infinity Pharmaceuticals, Inc.: lead
• Roche Pharma AG: collaborator

Study Sites (24)

Ironwood Cancer and Research Center

Chandler, Arizona, 85224, United States

Location

Arizona Oncology Associates

Tucson, Arizona, 85704, United States

Location

Arizona Clinical Research Center

Tucson, Arizona, 85715, United States

Location

St. Joseph Heritage Healthcare

Fullerton, California, 92835, United States

Location

Cancer & Blood Specialty Clinic

Los Alamitos, California, 90720, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

Samsum Clinic

Santa Barbara, California, 93105, United States

Location

UCLA

Santa Monica, California, 90404, United States

Location

Olive View - UCLA Medical Center

Sylmar, California, 91342, United States

Location

Valley Breast Cancer Care and Women's Health Center

Van Nuys, California, 15211, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Orlando Health

Orlando, Florida, 32806, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University Cancer & Blood Center

Athens, Georgia, 30607, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, 46804, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

UT Health East Texas HOPE Cancer Center

Tyler, Texas, 75701, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

Related Links

• IPI-549

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Renal Cell; Triple Negative Breast Neoplasms

Interventions

IPI-549; atezolizumab; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• Feng Chi, PhD, RN

  Medical Lead

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: April 8, 2019
• First Posted: May 23, 2019
• Study Start: December 17, 2019
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (24)