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352 Updated clinical data from the squamous cell carcinoma of the head and neck (SCCHN) expansion cohort of an ongoing Ph1/1b Study of eganelisib (formerly IPI-549) in combination with nivolumab
  1. Ezra Cohen1,
  2. Michael Postow2,
  3. Ryan Sullivan3,
  4. David Hong4,
  5. Heather Yeckes-Rodin5,
  6. Jerry McCarter6,
  7. Nora Zizlsperger6,
  8. Jeffery Kutok7,
  9. Brenda O’Connell6,
  10. Kara Page6,
  11. Jennifer Roberts6,
  12. Halle Zhang6 and
  13. Bartosz Chmielowski8
  1. 1University of California San Diego, La Jolla, CA, USA
  2. 2Memorial Sloan Kettering Cancer Center, New York, NY, USA
  3. 3Massachusetts General Hospital, Boston, MA, USA
  4. 4MD Anderson Cancer Center, Houston, TX, USA
  5. 5Heme-Onc Associates of Treasure Coast, Port St. Lucie, FL, USA
  6. 6Infinity Pharmaceuticals, Cambridge, MA, USA
  7. 7Epizyme, Cambridge, MA, USA
  8. 8University of California Los Angeles, Los Angeles, CA, USA


Background Eganelisib is a first-in-class, oral, selective PI3K-γ inhibitor. Preclinically, eganelisib reprograms macrophages/myeloid derived suppressor cells (MDSCs) from an immune-suppressive to an immune-activating phenotype and enhances efficacy of checkpoint inhibitors. Efficacy of eganelisib + nivolumab in patients with SCCHN resistant to immediate prior anti-PD(L)1 therapy is presented.

Methods IPI-549-01 (NCT02637531) evaluates eganelisib in advanced solid tumors, as monotherapy and in combination with nivolumab. The combination expansion dose was eganelisib 40 mg QD PO + nivolumab 240 mg Q2W IV. Combination expansion cohorts include SCCHN patients resistant to immediate prior anti-PD(L)1 therapy. Safety, preliminary clinical activity, PK, and correlative study of blood and tumor biopsy samples were mandated.

Results As of June 1, 2020, 180 patients were treated with eganelisib + nivolumab including 21 with SCCHN.The most common (>20% of patients) treatment-emergent adverse events in patients treated with eganelisib + nivolumab (N = 180) were fatigue (34.4%), increased AST (30.0%), increased ALT (26.7%), nausea (25.0%), pyrexia (25.0%), anemia (22.8%), decreased appetite (20.6%), and cough (20.6%). 85 (47.2%) patients experienced at least 1 treatment-emergent serious adverse event (SAE) and 19 (10.6%) had a treatment-related SAE. There were no treatment-related grade 5 adverse events as assessed by investigators. Preliminary data from the SCCHN cohort show that in the efficacy-evaluable population which includes all patients (n=20) who had at least 1 post-baseline response assessment or discontinued treatment due to disease progression, the overall response rate (ORR, ie. CR [complete response] or PR [partial response] per RECIST v1.1) is 10.0%, the disease control rate (DCR, ie. CR, PR, or SD [stable disease]) is 45.0%, and the clinical benefit rate (CBR, ie. CR, PR, or SD of at least 24 weeks from first treatment) is 25.0%, per RECISTv1.1. For patients that received ≤ 2 lines of prior systemic therapy (n=11), the ORR is 20.0%, the DCR is 40.0%, and the CBR is 30.0%. In total, there are 2 patients with PR (duration of response 1.6–9.3 months) and 3 with SD for greater than 6 months‘ treatment duration. Translational data including T cell proliferation in peripheral blood as well as markers of inflammation in baseline biopsy of PR patient will be presented.

Conclusions Eganelisib + nivolumab demonstrates an acceptable safety profile and preliminary clinical activity in patients with SCCHN who were resistant to immediate prior anti-PD(L)1 therapy. Updated clinical and translational data will be presented.

Ethics Approval The study was approved by WIRB, Study Number 1188591 and IRB Tracking Number: 20180297.

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