Working to improve front line TNBC regimens
About the MARIO 3 study
The MARIO-3 trial is investigating whether an investigational drug called eganelisib (IPI-549) could improve outcomes for patients newly diagnosed with triple negative breast cancer (TNBC), when added to a standard of care regimen. The main goal of the trial is to evaluate patients’ complete response to therapy, which means the absence of all detectable cancer after receiving treatment. If this approach is successful, it has the potential to enhance the standard of care for TNBC patients.
The trial is studying a “triple combination,” which includes the addition of a new investigational drug called eganelisib (IPI-549) to an FDA-approved combination treatment of a chemotherapy known as Abraxane and an immunotherapy (IO) known as Tecentriq for patients with TNBC. Eganelisib, which has already been studied in over 300 cancer patients in several combination regimens, is being investigated for its potential to enhance the effects of the chemotherapy and IO combination.
Each of the three drugs plays a specific role in helping control cancer:
- Chemotherapy (Abraxane) works to directly kill tumors
- Immunotherapy checkpoint inhibitors (Tecentriq) work with the immune system to activate T-cells, triggering an anti-tumor immune response to kill tumors
- Eganelisib (IPI-549) works to augment and maintain the body’s immune response by further activating an anti-tumor immune response and limiting the tumor’s ability to suppress this response, with the goal of sustaining T cell activity and preventing the tumor from growing back
- Patients must be over 18 years of age
- At least 1 measurable disease lesion by CT or MRI performed within 2 weeks prior to first dose
- Willing to undergo one ‘pre-treatment’ core biopsy (unless archival tumor tissue is available within 3 months of first dose), one ‘on-treatment’ tumor biopsy, unless not safe or medically feasible, and an optional biopsy within 30 days of the last dose of study treatment. Tumor tissue will be used for biomarker analysis including PD-L1 expression. PD-L1 Results are not required prior to start of study treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- Life expectancy ≥12 weeks
- Adequate baseline hematologic and organ function
- Metastatic or locally advanced, histologically documented TNBC, i.e., absence of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER) and progesterone receptor (PR) expression
- No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC. Radiation therapy for metastatic disease is permitted. There is no required minimum washout period for radiation therapy. Patients should be recovered from the effects of radiation. Prior treatment with taxanes in the neoadjuvant or adjuvant setting is allowable if treatment was completed ≥12 months prior to first treatment at C1D1. Prior treatment with non-taxane chemotherapy in the neoadjuvant or adjuvant setting is allowable if treatment was completed ≥ 6 months prior to first treatment at C1D1.
- Any history of, or currently active, brain or leptomeningeal metastases.
- Significant cardiovascular disease as defined in the study protocol.
- Major surgical procedure within 4 weeks prior to enrollment or the need for a major surgical procedure during the course of the study.
- Active tuberculosis. Ongoing systemic bacterial, fungal, or viral infections at Screening.
- Positive test for human immunodeficiency virus (HIV), HBV, HCV
- Dependence on continuous supplemental oxygen use.
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
- 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.
- History of stroke, transient ischemic attack, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to Screening.
- Other prior malignancy active within the previous 5 years except for local or organ confined early stage cancer that has been definitively treated with curative intent, does not require ongoing treatment, has no evidence of residual active disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the primary and secondary endpoints of the study, including response rate and safety.
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
- Prior therapy with experimental anti-tumor vaccines; any T cell co-stimulation or checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, including ipilimumab, or other medicines specifically targeting the T cell; or IPI-549.
- Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to enrollment, or anticipated requirement for systemic immunosuppressive medications during the trial. Exceptions apply as specified in the protocol.
- Uncontrolled tumor-related pain
Frequently Asked Questions
A clinical trial is a controlled study where an investigational drug is evaluated in humans. The purpose of a clinical trial is to evaluate the safety and efficacy (how well it works) of an investigational drug. To participate in a clinical trial, you must meet all eligibility criteria and be willing to following the directions of the study doctor. Throughout the study, a team of nurses, doctors and trial coordinators will be closely working with you. They will monitor any symptoms or changes and ensure you are comfortable and informed throughout the process.
No compensation will be provided, but all study drugs will be provided to you at no cost.
Previous studies have shown eganelisib (IPI-549) to be well tolerated and have also provided evidence suggesting that it has the potential to enhance the effects of the current standard of care, an IO and chemotherapy combination.
See below for a map of our current trial sites.