Addition of Imprime PGG to chemotherapy improved outcomes in NSCLC

The combination of carboplatin, paclitaxel and cetuximab plus the immunotherapy Imprime PGG induced response and improved survival in patients with late-stage, non–small cell lung cancer who had high levels of natural anti-beta glucan antibodies, according to phase 2 study results presented at the AACR-IASLC Joint Conference on the Molecular Origins of Lung Cancer.

Richard D. Huhn, MD, medical director and senior vice president at Biothera Inc., and colleagues enrolled 90 patients with stage IIIb or stage IV NSCLC to evaluate the efficacy of Imprime PGG (Biothera Inc.), a yeast-derived beta 1,3/1,6 glucan.

“Imprime PGG is an immunotherapy that capitalizes on a natural defense mechanism in our bodies through which … neutrophils and monocytes recognize and kill infectious organisms,” Huhn said in a press release. “When combined with an antitumor monoclonal antibody, Imprime PGG redirects neutrophils and monocytes to recognize and kill cancer.”

All patients received carboplatin and 200 mg/m2 paclitaxel on day 2 of each 3-week cycle for the first four to six cycles.

Researchers assigned 30 patients to a control arm. They received a 400-mg/m2 loading dose of cetuximab (Erbitux, Eli Lilly), followed by 250-mg/m2 maintenance doses.

The remaining 60 patients received cetuximab plus 4 mg/kg Imprime PGG on days 1, 8 and 15.

Patients who achieved radiographic stable disease or tumor responses (RECIST 1.0) continued maintenance therapy.

Twenty-six patients in the control arm and 46 in the Imprime PGG arm were evaluable for response. Those assigned to the control arm achieved longer median OS (11.2 months vs. 10.2 months; HR=1.06; P=.85).

However, 3-year OS was 0% in the control arm vs. 7% in the Imprime PGG arm.

Objective response rate was 23% in the control arm vs. 48% in the Imprime PGG arm (P=.048).

The researchers conducted additional biomarker analyses evaluating anti-beta glucan antibody levels conducive to the binding of Imprime PGG to CR3 on immune cells.

Median OS among 15 patients who were biomarker-positive in the Imprime PGG arm was 16.5 months (HR=0.63; P=.26 vs. control) and 9.1 months among 31 patients who were biomarker-negative in the Imprime PGG arm (HR=1.35; P=.35 vs. control).

Three-year OS was 17% among biomarker-positive patients vs. 0% in biomarker-negative patients.

Researchers reported an objective response rate of 48% in the Imprime group and 23% in the control group. In the Imprime group, the objective response rate was 67% among biomarker-positive patients (P=.009 vs. control) and 39% among biomarker-negative patients (P=.26 vs. control).

All adverse events were comparable to those typically associated with chemotherapy or cetuximab, researchers said. More patients in the control arm experienced a grade 3 or grade 4 adverse event compared with patients in the Imprime PGG arm (86% vs. 78%).

“We believe that Imprime PGG can change the way cancer is treated,” Huhn said in the press release. “The discovery of a biomarker-positive population may enable the enrichment of future clinical trials.”

For more information:

Thomas M. Abstract #A26. Presented at: AACR-IASLC Joint Conference on the Molecular Origins of Lung Cancer; Jan. 6-9, 2014; San Diego.

Disclosure: The researchers report employment with Biothera Inc. Biothera Inc. funded the study.