Background: CPI monotherapy provides substantial clinical benefit to patients (pts) in multiple cancers, yet response rates are limited (˜15-30%) and fails to benefit the majority. In these pts there is limited or no ongoing T cell-based immune response. Imprime PGG (Imprime), a novel beta glucan derived from Saccharomyces, may expand the clinical benefit of CPI therapy by stimulating an anti-cancer immune response. Acting as a pathogen-associated molecularpattern (PAMP), Imprime enlists innate immune functions including cytotoxic effector mechanisms, reversal of immunosuppression and cross-talk with the adaptive immune system.Imprime-mediated innate immune activation requires formation of an immune complex with naturally-occurring anti-beta glucan antibodies (ABA); sufficient ABA levels is required for complex formation. Imprime is now being studied in combination with pembrolizumab (KEYTRUDA®,Pembro), a humanized mAb against PD-1 which has been previously studied in TNBC pts.

Methods: In this study of patients who previously failed chemotherapy for metastatic TNBC, Imprime is being used in combination with Pembro in a Simon 2 stage design. Asample size of 12 evaluable pts in Stage 1 was planned.Evaluable pts received at least one dose of study treatment (tx), had measurable disease at baseline per RECIST v1.1, had at least one post-baseline scan or discontinued tx as a result of progressive disease, death, or a tx-related adverse event before the first post-baseline scan.Pts received Imprime (4 mg/kg IV days 1, 8, 15 of each 3-week cycle) + Pembro 200 mg on D1 of each cycle. Criteria to advance to Stage 2 were ≤4 grade 3/4 AEs during the first tx cycle (other than infusion reactions) and ≥1 objective response. Study primary endpoints are ORR and safety; secondary endpoints are TTR, CRR, DoR, PFS, and OS. Exploratory endpoints include ORR and PFS per irRECIST. Biopsies and blood samples are being collected to assess tx impact on immune activating events at the tumor site and in the periphery.

Results: A review of efficacy and safety data was conducted at the end of Stage 1. Thirteen pts (12 evaluable) were enrolled into Stage 1. Safety review noted 2 grade 3 adverse events that met protocol definition of Stage 1 events (1 pt: cellulitis and 1 pt: pleural infusion; both unrelated to treatment). Two events lead to 2 pts discontinuing treatment (infusion reaction and pancreatitis) and only 1 autoimmune event was observed (pancreatitis). Observed efficacy responses in the evaluable pts included 1 complete response (CR; ongoing) and 2 partial responses (PR; ongoing). Secondary efficacy endpoints have not been assessed. Early translational results support proposed MOA and analysis of Stage 1 translational data is ongoing.

Conclusion: The use of Imprime with Pembro was well tolerated and met both safety and efficacy requirements to move forward with Stage 2 of the study. No significant safety concerns were identified in Stage 1. Further investigation is thus warranted and enrollment into Stage 2 is ongoing. Updated data will be presented.

Citation Format: O'Day S, Borges V, Chmielowski B, Rao R, Abu-Khalaf M, Stopeck A, Lowe J, Mattson P, Breuer K, Gargano M, Bose N, Uhlik M, Graff J, Chisamore M, Cox J, Osterwalder B. Imprime PGG, a novel innate immune modulator, combined with pembrolizumab in a phase 2 multicenter, open label study in chemotherapy-resistant metastatic triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-08.