Pembrolizumab Plus Innate Immune Activator May Benefit Metastatic TNBC Patients

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: IMPRIME 1 trial results indicate that an innate immune activator may offer a novel approach to the treatment of metastatic triple-negative breast cancer (TNBC) when given alongside pembrolizumab. 

Imprime PGG is an immune complex formed between a beta glucan and endogenous antibodies that acts as an active drug designed to reprogram the tumour microenvironment, activate antigen presenting cells, and increase tumour-specific T cell activation and infiltration, said Steven O’Day, from the John Wayne Cancer Institute in Santa Monica, California, USA. 

Presenting the findings at the 2020 AACR Virtual Annual Meeting I, he said that the study showed “encouraging clinical benefit evidence across all clinical measures” in the 44 metastatic TNBC patients with a poor prognosis after initial non-immune checkpoint inhibitor therapy. 

Specifically, 15.9% of patients given intravenous Imprime PGG 4 mg/kg per week plus pembrolizumab 200 mg every 3 weeks achieved an objective response and 38.6% had stable disease, with disease control over a minimum of 24 weeks reported for 25.0% of the group. 

And Imprime PGG plus pembrolizumab achieved a “particularly pronounced” response among 12 women who had initially been diagnosed with hormone receptor-positive breast cancer that converted to TNBC after endocrine therapy, the presenter noted. 

The objective response rate (ORR) and stable disease rate were 50.0% and 33.0%, respectively, in this subgroup, with a 6-month disease control rate of 50.0%, he said, contrasting both sets of combination findings with those of the KEYNOTE-086 study of pembrolizumab monotherapy in a similar population, where the ORR was 5.3% and the 24-week disease control rate was 7.6%. 

Similarly, overall survival (OS) in the full combination therapy group was a median of 16.4 months, rising to 17.1 months in the converted TNBC subgroup, versus 9.0 months in the historical pembrolizumab monotherapy study. 

Steven O’Day also reported translational data demonstrating both innate and adaptive immune activation, with peripheral blood samples from 43 patients indicating a significant OS benefit among patients who did versus did not achieve an increase in CD86 monocyte expression (median 22.1 vs 11.1 months., hazard ratio [HR] for death=0.310) or T cell activation (22.1 vs 11.9 months, HR=0.334). 

In addition, paired slides of liver metastasis biopsies taken before and after combination therapy showed “robust” myeloid and T cell activation and infiltration, he said. 

Imprime PGG plus pembrolizumab was a “well-tolerated combination” with “no unexpected safety observations”, the presenter remarked. Grade 3–4 adverse events occurred in 9.0% of the participants, which included an infusion reaction in one patient and immune-mediated pericarditis and pancreatitis in one patient each. 

The investigator concluded that “larger controlled studies are warranted” for the combination regimen, especially among patients who have converted to TNBC after endocrine therapy. 

Reference  

O’Day SJ, Borges VF, Chmielowski B, et al. IMPRIME 1 (NCT02981303): A novel phase 2 study in second-line +, metastatic triple negative breast cancer patients shows promising clinical benefit for the combination of the immune checkpoint inhibitor, pembrolizumab (pembro), with the novel innate immune activator, Imprime PGG. American Association of Cancer Research Virtual Annual Meeting I; 27–28 April 2020 (Abstract CT073).