Infinity Reports IPI-549 Clinical and Translational Data from Ongoing Phase 1/1b Study at American Society of Clinical Oncology Annual Meeting

June 4, 2018 at 7:30 AM EDT
- IPI-549 Well Tolerated in Combination Dose Escalation with Nivolumab -
- Clinical Activity in Combination Dose Escalation in Indications Not Typically Responsive to Anti-PD1 Therapy Including Rapid, Deep and Durable Partial Responses in Two Patients, One with Adrenocortical Cancer and One with MSS Gallbladder Cancer -
- Translational Data Indicate Reduced Immune Suppression and Induced Immune Activation, Consistent with Mechanism of Action Demonstrated in Preclinical Studies -
- Enrollment Ongoing in Seven Combination Expansion Cohorts with Additional Clinical and Translational Data Expected in Second Half of 2018 -
- Company to Host Investor Webcast Today at 6:30 a.m. CT -

CAMBRIDGE, Mass., June 4, 2018 /PRNewswire/ -- Infinity Pharmaceuticals, Inc. (NASDAQ: INFI), announced that data to be presented today at the ASCO 2018 Annual Meeting demonstrates that IPI-549, a first-in-class immuno-oncology product candidate that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma), in combination with nivolumab was well tolerated and demonstrated evidence of clinical activity in indications not typically responsive to anti-PD1 therapy.i 40% (12 of 30) of evaluable patients demonstrated disease control with 10 patients with stable disease and two patients who achieved rapid, deep and durable partial responses, including one patient with adrenocortical cancer and one with microsatellite stable (MSS) gallbladder cancer. In addition, IPI-549 reduced immune suppression and induced immune activation, as indicated by analyses of peripheral blood and paired tumor biopsies.

"We were encouraged to see rapid, deep and durable responses in some patients with the combination of IPI-549 and nivolumab in dose escalation, and we look forward to continuing to evaluate this combination in specific patient populations through the seven combination expansion cohorts," said Dr. Ryan J. Sullivan, Massachusetts General Hospital, and an investigator on the IPI-549 Phase 1/1b study. "There remains a critical unmet need for patients with a number of solid tumors who do not benefit from anti-PD1 therapy, and IPI-549 in combination with nivolumab may offer an important therapeutic alternative."

IPI-549 combined with nivolumab in dose escalation was well tolerated at all doses tested, up to the recommended expansion dose of IPI-549 at 40mg once daily plus nivolumab at 240mg once every two weeks. No maximum tolerated dose (MTD) was determined, and there were no treatment-related deaths.  Additionally, the pharmacokinetic/pharmacodynamic profile of IPI-549 (up to 40mg QD) was unaffected by nivolumab co-administration.

IPI-549 as a monotherapy also continued to be well tolerated at all doses studied up to the recommended dose for expansion of 60 mg once daily. IPI-549 demonstrated evidence of monotherapy clinical activity, with one durable partial response in peritoneal mesothelioma, where a patient remains on study after 20 months.

"IPI-549 combined with nivolumab demonstrated compelling responses in two patients, one with adrenocortical cancer and one with MSS gallbladder cancer, and translational studies demonstrated evidence of on-mechanism IPI-549-mediated effects," said Adelene Perkins, Chief Executive Officer and Chair of Infinity Pharmaceuticals. "We are very pleased by the rapidity, depth and durability of the responses in combination with nivolumab, along with a promising safety profile. Enrollment in the seven combination expansion cohorts has been robust, and we look forward to reporting data in the second half of this year from these six disease-specific cohorts and a seventh cohort of patients selected for high baseline blood levels of myeloid derived suppressor cells. Data from these expansion cohorts will further inform our development and regulatory strategy for this first-in-class product candidate."

Data from peripheral blood and paired tumor biopsies suggest that IPI-549 reduces immune suppression and induces immune activation, consistent with the mechanism of action demonstrated in pre-clinical studies. Monotherapy paired tumor biopsies showed decreased CD163 M2 macrophage marker expression and peripheral blood data revealed a dose-related increase in proliferation of exhausted memory T cells on top of fixed-dose nivolumab. Finally, there is a statistically significant increase in exhausted T cell proliferation in combination dose escalation patients with tumor shrinkage. This statistically significant increase was also demonstrated in patients who remained on study for over 16 weeks.

The data will be presented in three events today during the American Society of Clinical Oncology Annual Meeting.

Investor Event 6:30 a.m. CT – 7:30 a.m. CT
Infinity Pharmaceuticals is hosting an investor event on this morning at 6:30 a.m. CT with Dr. Ryan Sullivan from Massachusetts General Hospital, an investigator on the IPI-549 Phase 1/1b study, to review the IPI-549 data being presented at ASCO. The event will be webcast live and can be accessed on the Investors/Media section of Infinity's website at for 30 days following the event.

Poster Session 8:00 a.m. CT – 11:00 a.m. CT
 Initial results from first-in-human study of IPI-549, a tumor macrophage-targeting agent, combined with nivolumab in advanced solid tumors. 
Session Title: Developmental Therapeutics – Immunotherapy  
Session Date and Time: Monday, June 4, 2018, 8:00 a.m. CT – 11:00 a.m. CT  
Poster Board: 227 
Abstract Number: 3013   
First Author: Ryan J. Sullivan, MD, Massachusetts General Hospital
Location: Hall A, McCormick Place convention center 

Poster Discussion Session 11:30 a.m. CT – 12:45 p.m. CT
 Initial results from first-in-human study of IPI-549, a tumor macrophage-targeting agent, combined with nivolumab in advanced solid tumors. 
Session Title: Developmental Therapeutics – Immunotherapy 
Session Date and Time: Monday, June 4, 2018, 11:30 a.m. CT – 12:45 p.m. CT
Abstract Number: 3013
First Author: Ryan J. Sullivan, MD, Massachusetts General Hospital
Location: Hall B1, McCormick Place convention center

About IPI-549 and the Ongoing Phase 1/1b Study
IPI-549 is an investigational first-in-class, oral, immuno-oncology product candidate targeting tumor-associated myeloid cells through selective phosphoinositide-3-kinase-gamma (PI3K-gamma) inhibition, thereby reducing pro-tumor macrophage function and increasing anti-tumor macrophage function. In preclinical studies, IPI-549 demonstrated the ability to reprogram macrophages from a pro-tumor (M2), immune suppressive function, to an anti-tumor (M1) immune activating function and enhance the activity of, and overcome resistance to, checkpoint inhibitors.ii iii As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially additive or synergistic approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

The ongoing Phase 1/1b study being conducted by Infinity is designed to evaluate the safety, tolerability, activity, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with nivolumab (Opdivo®) in approximately 200 patients with advanced solid tumors.iv The study includes monotherapy and combination dose-escalation components, in addition to monotherapy expansion and combination expansion components. The monotherapy dose-escalation and expansion components are complete. The combination dose-escalation component is also complete, and combination expansion cohorts are enrolling.

The combination expansion component of the study includes multiple cohorts designed to evaluate IPI-549 in patients with specific types of cancer, including patients with non-small cell lung cancer (NSCLC), melanoma and head and neck cancer whose tumors show initial resistance or initially respond to but subsequently develop resistance to immune checkpoint blockade therapy. The combination expansion component also includes a cohort of patients with triple negative breast cancer (TNBC) who have not been previously treated with immune checkpoint blockade therapy, a cohort of patients with mesothelioma, a cohort of patients with adrenocortical carcinoma and a cohort of patients with high baseline blood levels of MDSCs.

IPI-549 is an investigational compound and its safety and efficacy has not been evaluated by the U.S. Food and Drug Administration or any other health authority.

About Infinity 
Infinity is an innovative biopharmaceutical company dedicated to advancing novel cancer treatments. Infinity is advancing IPI-549, a potentially transformative immuno-oncology approach that aims to reprogram tumor-associated macrophages by selectively inhibiting PI3K-gamma. A Phase 1/1b study in approximately 200 patients with advanced solid tumors is ongoing. For more information on Infinity, please refer to Infinity's website at

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 PI3K-gamma selective inhibition and IPI-549, alone and in combination with checkpoint inhibitors, including Opdivo®, and plans to report clinical and translational data of IPI-549. 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 IPI-549 will successfully complete necessary preclinical and clinical development phases or 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: Infinity's results of clinical trials and preclinical studies; a failure of Infinity and/or Verastem to fully perform under the license agreement; 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 and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of agents by Infinity's competitors for diseases in which Infinity is currently developing or intends to develop IPI-549; and Infinity's ability to obtain, maintain and enforce patent and other intellectual property protection for IPI-549.These and other risks which may impact management's expectations are described in greater detail under the caption "Risk Factors" included in Infinity's quarterly report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 8, 2018, and other filings filed by Infinity with the SEC.  Any forward-looking statements contained in this press release speak only as of the date hereof, and Infinity expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

OPDIVO® is a registered trademark of Bristol-Myers Squibb.

Stephanie Ascher
Stern Investor Relations, Inc. 

i ORR to PD1 inhibition in ACC 9% (1/11)-- Habra et al, SITC 2017
ii Kaneda, M., Messer, K., Ralainirina, N., Li, H., et al. PI3Kγ is a molecular switch that controls immune suppression. Nature, 2016 Nov;539:437–442.
iii De Henau, O., Rausch, M., Winkler, D., Campesato, L., et al. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells. Nature, 2016 Nov;539:443-447., NCT02637531.

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SOURCE Infinity Pharmaceuticals, Inc.