Biothera Pharmaceuticals Presents Immune Pharmacodynamic Data (IPD) Showing Immune Activation in Phase 2 Melanoma and Triple Negative Breast Cancer Study
Two Late-Breaking Poster Presentations at the Society for Immunotherapy of
Cancer (SITC) Annual Meeting
Imprime PGG-induced IPD Changes Associated with
Stable Disease, Progression-Free Survival and Overall Survival
EAGAN, MN — November 8, 2019 — Biothera Pharmaceuticals, Inc. announced today immune pharmacodynamic data from its Phase 2 clinical study evaluating the therapeutic combination of Imprime PGG and KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in chemo-refractory metastatic triple negative breast cancer (mTNBC) patients and metastatic melanoma patients who have failed immune checkpoint inhibitor (CPI) therapy. The data are being presented in two late-breaking posters at the Society for Immunotherapy of Cancer’s annual meeting on November 8 and 9 in National Harbor, MD.
Analyses of peripheral blood samples taken over the course of the IMPRIME 1 study show that Imprime PGG, a dectin receptor agonist, induced anti-tumor immune responses culminating in a substantial increase in activated killer T cells. “These data provide key evidence that Imprime PGG, in combination with pembrolizumab, successfully activates T cells, particularly in patients who realize the greatest clinical benefit,” said Jeremy Graff, Ph.D., President and Chief Scientific Officer of Biothera Pharmaceuticals.
IMPRIME 1 Study Results
In three previous mTNBC studies, CPI monotherapies resulted in a disease control rate of
7-10% (CR +PR+ SD >24 weeks), median overall survival (mOS) of 7-9 months and a 12-month OS of 37-40%. Primary data from the 44-patient Phase 2 study evaluating Imprime PGG and KEYTRUDA show a disease control rate of 25% (N= 11; 1 CR, 6 PR and 4 SD>24 weeks), mOS of 16.4 months and 12-month OS rate of 57.6%.
Translational analysis of blood samples from 41 patients found Imprime PGG successfully elicited serum and cellular immune pharmacodynamic changes (e.g., Anti-beta glucan antibody levels, circulating immune complexes, complement activation, cytokine/chemokine and gene expression changes) in patients who showed the greatest clinical benefit.
Similar results were observed in the melanoma arm of the study, which tested the combination of Imprime PGG and KEYTRUDA in heavily CPI pre-treated melanoma patients (20 patients; 13/20 had >2 prior CPI regimens and 17/20 had progressed on pembrolizumab). The disease control rate was 50% (1 CR and 9 SD as best response), 12-month OS rate was 45%.
“In this difficult to treat population, we see clear evidence that Imprime PGG re-awakened the immune system and triggered robust anti-cancer immune responses critical to effective CPI therapy,” said Dr. Graff. “In both melanoma and TNBC patients there is a compelling link between the mechanistic data and clinical benefit of combining Imprime PGG with CPI therapy. This proof of concept study gives us the confidence to advance the clinical development of Imprime PGG.”
Late-Breaking Poster Presentations at SITC
The IMPRIME 1 IPD data will be presented during the late-breaking poster sessions from 7:00 a.m. – 8:30 p.m. ET on both Friday, November 8 and Saturday, November 9.
- Poster #P862
Clinical benefit potentially evident with immunopharmacodynamic responses in prior-checkpoint failed metastatic melanoma patients treated with Imprime PGG and pembrolizumab
- Poster #P859
Association of immunopharmacodynamic responses of Imprime PGG plus pembrolizumab with clinical benefit in metastatic triple negative breast cancer (TNBC) subjects failing front-line chemotherapy
IMPRIME 1 Study Design
IMPRIME 1 is an open-label Phase 2 trial (clinicaltrials.gov, NCT02981303) evaluating whether Imprime PGG can enhance sensitivity to checkpoint inhibitors through activation of the innate and adaptive immune systems in heavily CPI pre-treated melanoma patients and mTNBC patients who have failed one or more lines of therapy and were CPI-naïve. A biomarker was used to select patients who were most likely to respond to Imprime PGG. Patients received Imprime PGG (4 mpk IV weekly) + KEYTRUDA (200 mg IV q3w) until disease progression or intolerable toxicity.
The primary endpoint was ORR by RECIST v1.1 and safety, and secondary endpoints included OS and DCR. Pre- and on-therapy tumor biopsies were collected to assess immune activation at the tumor site. The tissue samples showed that Imprime PGG induced heavy infiltration of tumor tissues by activated innate immune cells (M1 state, PD-L1+) and activated CD8 and CD4 T cells. On-treatment peripheral blood samples showed Imprime PGG-specific innate immune cell mobilization and activation, as well as enhanced T cell activation.
About Biothera Pharmaceuticals, Inc.
Biothera Pharmaceuticals is a privately held biotechnology company developing Imprime PGG, a novel dectin receptor agonist that reverses tumor-mediated immunosuppression while promoting antigen presentation to drive T cell activation and infiltration into tumors and to enhance clinical benefit from immune checkpoint inhibitors. Biothera Pharmaceuticals is currently developing this platform drug through clinical research collaborations with Merck, Genentech, Dana Farber Cancer Institute and the Big Ten Cancer Research Consortium in cancers that include triple negative breast cancer, advanced melanoma, colorectal cancer and non-small lung cell cancer.
Jeremy Graff, Ph.D.
President and Chief Scientific Officer
Biothera Pharmaceuticals, Inc.