Infinity Pharmaceuticals Presents Updated Data from Phase 2 MARIO-275 Trial in Urothelial Cancer (UC) and Phase 2 MARIO-3 Trial in Triple Negative Breast Cancer (TNBC)
– MARIO-275 median overall survival data show combination of eganelisib with nivolumab achieves 15.4 months compared to 7.9 months on nivolumab control arm in 2L UC -
- MARIO-3 TNBC early data suggest the addition of eganelisib to standard of care regimens extends progression free survival regardless of PD-L1 status with majority of patients still on treatment –
- 86.8% of evaluable 1L patients with TNBC in MARIO-3 achieved tumor reduction with a total disease control rate of 84.2% –
- MARIO-275 and MARIO-3 translational data demonstrated on-mechanism increased immune activation and decreased immune suppression -
- KOL event scheduled for today,
MARIO-275 Key Data Updates:
49 patients were enrolled in the trial with the last patient enrolled in
Median overall survival (mOS) in the intent to treat (ITT) population was 15.4 months (6.2, NE) on the eganelisib plus nivolumab combination arm as compared to 7.9 months (2.3, NE) on the control arm of nivolumab alone with a hazard ratio of 0.62 (0.28, 1.36), which reflects a 38% lower probability of death on the combination arm.
- At the one-year landmark, 59% of patients in the ITT population receiving the eganelisib plus nivolumab combination remained alive, compared to 32% in the nivolumab control arm.
The mOS benefit observed in patients with PD-L1(-) tumors was the same as in the ITT population, with a mOS of 15.4 months (4.7, NE) on the eganelisib plus nivolumab combination arm as compared to 7.9 months (1.9, NE) on the control arm of nivolumab alone with a hazard ratio of 0.60 (0.21, 1.71), which reflects a 40% lower probability of death on the combination arm.
- At the one-year landmark, 54% of the patients with PD-L1(-) tumors receiving the eganelisib plus nivolumab combination remained alive, compared to 17% in the nivolumab control arm.
- The most common treatment emergent adverse events (TEAEs) across all doses, all causality, were pyrexia (33.3%), decreased appetite (30.3%), pruritus (27.3%), asthenia (27.3%), rash (27.3%), disease progression (27.3%) and increased alanine aminotransferase (24.2%); and the most common ≥Grade 3 TEAEs across all doses, all causality, were disease progression (27.3%), anemia (12.1%), and hepatic AEs including hepatotoxicity (15.2%), increased ALT (12.1%) and increased AST (12.1%) with no Hy’s Law. No Grade 5 hepatic AEs were reported.
- Translational data: Gene expression studies from peripheral blood, followed by gene set enrichment analysis using Hallmark gene signature sets show the pro-inflammatory interferon gamma and interferon alpha pathways were the most significantly enriched pathways in the combination arm when comparing Day 15 to baseline, regardless of PD-L1 status, with higher enrichment scores and lower p values than on the control arm. These data are consistent with eganelisib’s mechanism of action which decreases immune suppression and increases immune activation.
MARIO-3 Key Data Updates:
This data update includes 43 patients enrolled with 38 evaluable, which compares to 20 patients enrolled with 13 evaluable at our update at the San Antonio Breast Cancer Symposium in
- 86.8% (33/38) of evaluable patients demonstrated tumor reduction.
Disease control rate (DCR)
- 78.2% (18/23) DCR in patients with PD-L1 negative tumors: complete response (CR) 0% (0/23), partial response (PR) 47.8% (11/23), stable disease (SD) 30.4% (7/23)
- 91.7% (11/12) DCR in patients with PD-L1 positive tumors: CR 16.7% (2/12), PR 50% (6/12), SD 25% (3/12)
- 84.2% (32/38) DCR in all patients: CR 5.3% (2/38), PR 50% (19/38), SD 28.9% (11/38)
Early progression free survival (PFS)
- In patients with PD-L1(-) tumors, PFS was extended as compared to benchmark data for atezolizumab and nab-paclitaxel alone, increasing from 5.6 months to 7.3 months (3.5, NA).
- In patients with PD-L1(+) tumors, PFS was extended as compared to benchmark data for atezolizumab and nab-paclitaxel alone, increasing from 7.5 to 11.2 months (5.3, 11.2).
- In the ITT population, PFS was extended as compared to benchmark data for atezolizumab and nab-paclitaxel alone, increasing from 7.2 months to 7.4 months (5.3, NA).
- MARIO-3 did not demonstrate any new or additive safety signals compared to benchmark trials. The most common TEAEs, all causality, were nausea (51.2%), fatigue (48.8%), alopecia (32.6%), diarrhea (32.6%), rash maculo-papular (30.2%) increased ALT (27.9%) with only one Grade 4 and increased AST (25.6%) with one grade 4. No Hy’s Law or Grade 5 hepatic AEs were reported, and only one patient permanently discontinued study treatment due to an elevated liver function test.
- Quantification across 11 paired tumor biopsies shows increased immune activation and decreased immune suppression including an increase in CD8+ T cells, activated T cells, and anti-tumor M1 macrophages and a decrease in tumor cells and pro-tumor M2 macrophages resulting in an increase in the M1:M2 ratio.
- Paired tumor biopsy data show 5 of 8 patients with PD-L1(-) tumors converting to PD-L1(+) two months after treatment utilizing the 1% PD-L1 cutoff standard. PD-L1 expression also increased in the three patients with PD-L1(+) tumors who started the study above the 1% cutoff. None of the patients converting to PD-L1(+) or patients with PD-L1(+) tumors who experienced increased PD-L1 expression had disease progression.
KOL Event Information
In lieu of an earnings conference call, Infinity will host a KOL event today,
To register for the webinar, please click here.
About Infinity and Eganelisib
Infinity is an innovative biopharmaceutical company dedicated to advancing novel medicines for people with cancer. Infinity is advancing eganelisib, a first-in-class, oral immuno-oncology development candidate that selectively inhibits PI3K-gamma, in multiple clinical studies. MARIO-275 is a global, randomized, controlled combination study of eganelisib combined with Opdivo® in I/O naïve urothelial cancer. MARIO-3 is the first eganelisib combination study in front-line advanced cancer patients and is evaluating eganelisib in combination with Tecentriq® and Abraxane® in front-line TNBC and in combination with Tecentriq and Avastin® in front-line RCC. In collaboration with Arcus Biosciences, Infinity is evaluating a checkpoint inhibitor-free, novel combination regimen of eganelisib plus etrumadenant (AB928, a dual adenosine receptor antagonist) plus Doxil® in advanced TNBC patients. In 2019, Infinity completed enrollment in MARIO-1, a Phase 1/1b study evaluating eganelisib as a monotherapy and in combination with Opdivo (nivolumab) in patients with advanced solid tumors including patients refractory to checkpoint inhibitor therapy. With these studies Infinity is evaluating eganelisib in the anti-PD-1 refractory, I/O-naïve, and front-line settings. For more information on Infinity, please refer to Infinity's website at www.infi.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding: the therapeutic potential of eganelisib; registration trial planning; plans to present data; clinical trial enrollment projections; the timing of further clinical trial updates from the Company; and the Company's ability to execute on its strategic plans. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company's current expectations. For example, there can be no guarantee that eganelisib will successfully complete necessary preclinical and clinical development phases. Further, there can be no guarantee that any positive developments in Infinity's product portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the cost, timing and results of clinical trials and other development activities that may be delayed or disrupted by the COVID-19 pandemic or otherwise; the content and timing of decisions made by the
Opdivo® is a registered trademark of Bristol Myers Squibb.
Tecentriq® is a registered trademark of
Abraxane® is a registered trademark of
Avastin® is a registered trademark of
Doxil® is a registered trademark of