FDA Grants Fast Track Designation to Eganelisib Combination in TNBC

September 29, 2020

A Fast Track designation was granted by the FDA to eganelisib in combination with an immune checkpoint inhibitor and chemotherapy for the first-line treatment of patients with inoperable locally advanced or metastatic triple-negative breast cancer.

A Fast Track designation was granted by the FDA to eganelisib (IPI-549) in combination with an immune checkpoint inhibitor and chemotherapy for the first-line treatment of patients with inoperable locally advanced or metastatic triple-negative breast cancer (TNBC), Infinity Pharmaceuticals announced in a press release.1

This designation follows another Fast Track designation issued to the drug in combination with nivolumab (Opdivo) for the treatment of patients with advanced urothelial carcinoma, a combination being evaluated in the MARIO-275 clinical trial (NCT03980041).

“Fast Track designation is an exciting regulatory milestone that bolsters our momentum in TNBC,” said Adelene Perkins, chief executive officer and chair of Infinity Pharmaceuticals, in a statement. “TNBC remains the deadliest form of breast cancer, and there is tremendous need to expedite the development of new treatments that have the potential to improve outcomes in these patients.”

Eganelisib combined with atezolizumab (Tecentriq) and nab-paclitaxel as treatment of patients with TNBC will be investigated in the phase 2, multi-arm, open-label, MARIO-3 study (NCT03961698). The study is a collaborative effort between Roche and Infinity Pharmaceuticals, Inc.2 The primary end point being explored is the complete response rate per RECIST v1.1. Secondary end points in MARIO-3 include the incidence of treatment-emergent adverse events (AEs), the incidence of serious AEs, changes from baseline in electrocardiograph results, objective response rate, time to complete remission, time to response, duration of response, progression-free survival, and pharmacokinetics.1

Eligible patients are aged 18 years or older with measurable disease, an ECOG performance status us ≤1, and a life expectancy of at least 12 weeks. Patients are also required to have adequate baseline laboratory values within 14 das of dosing with any study drug.

Certain comorbidities and infections were grounds for exclusion from the study. In addition, prior treatment with anti-tumor vaccines, systemic immunostimulatory agents, systemic corticosteroids, or prior surgery with 4 weeks of enrollment, allogeneic stem cell transplantation, or solid organ transplantations were included in the exclusion criteria.

“We believe that adding eganelisib on top of standard of care in a novel triple combination front-line regimen with Tecentriq and Abraxane has the potential to provide meaningful benefits to patients and are particularly encouraged by the early signals of clinical activity we have seen in MARIO-3 to date. We look forward to presenting these important data later this year,” Perkins added.

The MARIO-3 study has a target completion date of 2022.

Enganelisib is a first-in-class immunotherapy agent with the ability to selectively inhibit PI3K-gamma, according to multiple clinical trials. In addition to TNBC, the drug is being used to treat renal cell carcinoma and other solid tumors. Ongoing clinical trials involving enganelisib include the previously mentioned MARIO-275, as well as the phase 1/1b first-in-human, dose-escalation study MARIO-1 (NCT02637531).

References:

Infinity receives Fast Track Designation for eganelisib in combination with a checkpoint inhibitor and chemotherapy for first-line treatment of advanced TNBC. News release. September 29, 2020. Accessed September 29, 2020. https://bit.ly/3imQjYR

Infinity to initiate MARIO-3, a phase 2 multi-arm study evaluating IPI-549 in front-line triple negative breast cancer and renal cell cancer. News release. March 14, 2019. Accessed September 29, 2020. https://bit.ly/2ScftyE