On February 11, 2021 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) ("Infinity" or the "Company") reported data from MARIO-275 (MAcrophage Reprogramming in Immune Oncology), a randomized, placebo-controlled Phase 2 study evaluating the efficacy and safety of eganelisib in combination with nivolumab (Opdivo) in platinum-refractory, I/O naïve patients with advanced urothelial cancer (UC) during the 2021 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) (Press release, Infinity Pharmaceuticals, FEB 11, 2021, View Source [SID1234574938]). The objective of MARIO-275 was to address the need for better treatments for second line (2L) advanced UC patients.

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"These encouraging data demonstrate that the addition of eganelisib to the approved 2L standard of care nivolumab monotherapy is well-tolerated with the potential to improve outcomes, including progression free survival, in patients with advanced urothelial cancer," said Piotr Tomczak, M.D., Ph.D., Medical Oncologist affiliated with Centrum Medyczne Pratia in Poznan, Poland, and MARIO-275 Lead Study Investigator. "We see the greatest benefit of combination therapy with eganelisib in the PD‑L1 negative patient population, with a disease control rate four times greater in the combination arm versus control arm. This is a promising advancement that has the potential to address the significant needs of PD-L1 low patients, which represent the majority of metastatic urothelial cancer population."

Brian Schwartz, M.D., consulting Chief Physician of Infinity, said, "We are excited to report that the addition of eganelisib on top of 2L standard of care nivolumab led to clear benefits for PD-L1 low patients, with an over 85% increase in overall response rate versus the control arm. These results, in combination with other efficacy measures, including prolonged progression free survival, are particularly meaningful given that the PD-L1 low patient population has historically poor overall response rates to checkpoint inhibitors of approximately 16%. We have now demonstrated on-mechanism translational activity across MARIO-1, MARIO-3 and MARIO-275, supporting the ability of eganelisib to reprogram macrophages to reduce immune suppression in the tumor microenvironment and expand the patient population that may benefit from treatment with checkpoint inhibitors. Based on the strength of these data and the magnitude of the unmet need in the PD-L1 low population, we are planning a registration-enabling study in advanced urothelial cancer and also are exploring the potential of eganelisib in PD-L1 low patients more broadly across cancer types."

Key presentation highlights:

Poster presentation titled, "Preliminary Analysis of a Phase 2, Multicenter, Randomized, active-Control Study to Evaluate the Efficacy and Safety of Eganelisib (IPI-549) in Combination with Nivolumab Compared to Nivolumab Monotherapy in Patients with Advanced Urothelial Carcinoma" presented by Piotr Tomczak, M.D., Ph.D.

Efficacy Results:

PD-L1 Negative Study Population

Greatest benefit of eganelisib with nivolumab combination therapy over nivolumab monotherapy was observed in the PD-L1 negative patient population (n=23) with improvement over nivolumab monotherapy (n=7) for overall response rate (ORR) (26% vs. 14%); disease control rate (DCR) (57% vs. 14%); and best responses of complete response (CR) (9% vs. 0%), and stable disease (SD) (30% vs. 0%)
PD-L1 negative patients demonstrated an extended progression free survival (PFS) with a hazard ratio of 0.54 reflecting a 46% reduction in probability of progression (mPFS of 9.1 weeks on combination arm versus 7.9 weeks on control arm)
58% (11/19) of PD-L1 negative patients receiving eganelisib in combination with nivolumab achieved a reduction in tumor burden versus 17% (1/6) in the placebo arm with nivolumab monotherapy
Overall Study Population

In the overall population, the combination of eganelisib with nivolumab demonstrated an increase over nivolumab monotherapy in ORR (30% vs. 25%); DCR (55% vs. 31%); and best responses of CR (12% vs. 6%), and SD (24% vs. 6%)
Nivolumab monotherapy in the control arm of MARIO-275 demonstrated response rates consistent with nivolumab monotherapy in CheckMate-275
Patients were stratified by MDSC level, but there was no meaningful difference between the disease control rate in the myeloid derived suppressor cells (MDSCs) high combination arm (29%, n=7) versus the MDSC high control arm (33%, n=3)
Safety Results:

33 patients received eganelisib at doses between 40 mg and 30 mg, once daily, plus nivolumab, and 16 patients received nivolumab monotherapy plus placebo
The dose reduction from 40 mg to 30 mg was to address reversible liver enzyme elevations reported at the first scheduled MARIO-275 Independent Data Monitoring Committee (IDMC) meeting
The median average daily dose of eganelisib in the study was 31.5 mg which supports 30mg as the dose for the registration-enabling study being planned
The IDMC supported further exploration of this combination therapy for patients after the successful implementation of the dose reduction
The combination of eganelisib and nivolumab was well tolerated at the 30 mg once daily dose
The most common treatment emergent adverse events (TEAEs) across all doses, all causality, were pyrexia (33%), decreased appetite (33%), pruritus (24%), rash (24%) and increased alanine aminotransferase (24%) and the most common ≥Grade 3 TEAEs across all doses, all causality, were disease progression (24.2%), hepatotoxicity (24.2%), increased ALT (12.1%) and increased AST (12.1%) with no Hy’s Law
No Grade 5 TEAEs were reported
Translational Results:

Increased immune activation was observed in eganelisib with nivolumab combination therapy compared to nivolumab monotherapy across PD-L1 negative and PD-L1 positive patients as measured by increased T cell reinvigoration
Decreased immune suppression was observed in eganelisib with nivolumab combination therapy compared to nivolumab monotherapy across PD-L1 negative and PD-L1 positive patients as measured by reduced levels of circulating MDSCs
The poster presented at ASCO (Free ASCO Whitepaper) GU can be accessed on the Infinity website at Investor Events and Presentations.

Conference Call Information

A live webcast of the conference call with synchronized slides can be accessed in the "Investors/Media" section of Infinity’s website at www.infi.com. To participate in the conference call, please dial (877) 316-5293 (domestic) and (631) 291-4526 (international) five minutes prior to start time. The conference ID number is 2485636. An archived version of the webcast will be available on Infinity’s website for 30 days.