Imprime PGG (I) is a yeast-derived beta-glucan PAMP administered systemically. It binds endogenous ABA to form immune complexes opsonized by complement, which trigger immune cell activation. Combination Ph 2 trials with monoclonal antibodies (mAbs) in over 300 cancer pts have shown increased clinical benefit, including PFS and OS, enhanced in ABA+ patients.
PRIMUS was a Ph 3, open-label, multi-center randomized study of cetuximab + Imprime PGG in 3rd line K-RAS wild type mCRC pts. 217 pts were randomized 2:1 to doublet vs. singlet. Cetuximab (Erbitux®) (E) was given as per package insert and I at 4mg/kg, IV, over 2 h, weekly. Pts were treated until progression (by RECIST 1.1). Primary endpoint was OS in the Intent to Treat (ITT) population. Secondary endpoints included PFS, ORR, Time to Response (TTR), and Response Duration (RD). Translational prospective analyses included relationship of ABA levels with clinical outcomes in the evaluable population.
140 pts were randomized to I + E and 77 to E. The study closed early due to low accrual. Median OS in the ITT population was 15.1 mo. for E and 10.7 mo. for I + E. (log-rank p = 0.047). Post-progression therapy was higher for E (58%) than for I + E (46%). ORR was 10% for E and 7% for I + E (p = 0.45). TTR was shorter for I + E (1.41 mo.) than for E (2.58 mo., log-rank p = 0.03). RD was longer for I + E (7.20 mo.) than for E (4.21 mo. (log rank p = 0.36). There was no difference in PFS [4.07 mo. for I + E and 4.11 mo. for E (log-rank p = 0.11)]. Correlative analysis of OS and PFS with ABA levels showed that pts with baseline IgG ABA of >35 µg/mL, when compared to those with
I + E did not improve OS or PFS vs. E alone. Levels of IgG ABA >35 µg/mL correlated with a statistically significant increase in PFS and OS in pts receiving I+ E, but not in those receiving E alone. Further validation studies of this Imprime PGG-specific biomarker and its correlation with clinical outcomes are warranted.
Clinical trial identification
Legal entity responsible for the study
M. Patchen, M.A. Gargano, B. Ma, J. Lowe, J.L. Iglesias: Employee of Biothera Pharmaceuticals and receives stock options as part of her compensation. All other authors have declared no conflicts of interest.