Infinity Pharmaceuticals Presents Data from Randomized, Placebo-Controlled, Phase 2 MARIO-275 Trial of Eganelisib & Nivolumab...
11 February 2021 - 11:15PM
Business Wire
- Combination of eganelisib with nivolumab
demonstrated improved ORR, DCR, and PFS versus 2L standard of care
nivolumab monotherapy -
- 46% lower probability of progression on
combination arm versus control arm in PD-L1 negative patient
population representing the majority of metastatic UC patients
-
- Planning registration-enabling study in PD-L1
low metastatic UC -
- Conference call scheduled for today, February
11, 7:30 am ET -
Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) (“Infinity” or the
“Company”) today presented 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 Genitourinary Cancers Symposium (ASCO GU). The objective of
MARIO-275 was to address the need for better treatments for second
line (2L) advanced UC patients.
“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 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.
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,
placebo-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 (dual
adenosine receptor antagonist) plus Doxil® in advanced TNBC
patients. 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, as amended. Such forward-looking statements include those
regarding: the therapeutic potential of eganelisib; including the
potential of eganelisib to improve outcomes, including progression
free survival, in patients with advanced urothelial cancer; the
potential benefit of combination therapy with eganelisib in the
PD-L1 negative patient population and the potential of eganelisib
in PD-L1 low patients more broadly across cancer types; plans for a
registration-enabling study in urothelial cancer 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 outcome of the Company’s risk/benefit
review of its MARIO-275 clinical trial; the content and timing of
decisions made by the U.S. FDA and other regulatory authorities;
Infinity's ability to obtain and maintain requisite regulatory
approvals; unplanned cash requirements and expenditures;
development of agents by Infinity's competitors for diseases in
which Infinity is currently developing or intends to develop
eganelisib; and Infinity's ability to obtain, maintain and enforce
patent and other intellectual property protection for eganelisib.
These and other risks which may impact management's expectations
are described in greater detail under the caption "Risk Factors"
included in Infinity's Annual Report on Form 10-K and Quarterly
Reports on Form 10-Qfiled with the Securities and Exchange
Commission (SEC), and in other filings that Infinity makes with the
SEC, available through the Company’s website at www.infi.com. Any
forward-looking statements contained in this press release speak
only as of the date hereof, and Infinity does not undertake and
expressly disclaims any obligation to update any forward-looking
statements, whether as a result of new information, future events
or otherwise.
Tecentriq® is a registered trademark of Genentech, Inc. Avastin®
is a registered trademark of Genentech, Inc. Abraxane® is a
registered trademark of Abraxis BioScience, LLC, a wholly owned
subsidiary of Bristol Myers Squibb Company. Opdivo® is a registered
trademark of Bristol Myers Squibb. Doxil® is a registered trademark
of Baxter Healthcare Corporation.
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