Abstract A26: Imprime PGG improves the efficacy of carboplatin, paclitaxel, and cetuximab chemoimmunotherapy of advanced non-small cell lung cancer (NSCLC).

Abstract

Abstract Imprime PGG is a yeast-derived beta 1,3/1,6 glucan that primes innate immune cells to kill monoclonal antibody (MAb)-targeted cancer cells via a mechanism dependent on complement receptor 3 (CR3). In humans, naturally occurring anti-beta glucan antibodies are required for binding of Imprime PGG to CR3 on immune cells. A quantitative assay has been developed to measure these antibodies in serum; subjects with levels conducive to binding are considered “biomarker positive” (BM+) and others “biomarker negative” (BM-). In a Phase 2 study, stage IIIb or IV NSCLC subjects received cetuximab (250 mg/m2 following initial 400 mg/m2 loading dose) without (Control, N=30) or with Imprime PGG 4mg/kg (Imprime, N=60) on Days 1, 8 and 15 of each 3-week treatment cycle; all subjects also received carboplatin (AUC 6) plus paclitaxel (200 mg/m2) on Day 2 of each cycle for the first 4 to 6 cycles. Maintenance treatment with cetuximab alone or with Imprime was continued in subjects achieving radiographic stable disease or tumor responses (RECIST 1.0). In the efficacy population comprised of all treated subjects who had evaluable baseline and post-baseline scans, median overall survival was 11.2 mo in the control group (N=26), 10.2 mo in the entire Imprime group (N=46) (HR 1.06, p=0.85 vs. control), 16.5 mo in the BM+ Imprime group (N=15) (HR 0.63, p=0.26 vs. control) and 9.1 mo in the BM- Imprime group (N=31) (HR 1.35, p=0.35 vs. control). Three-year survival was 0% in the control group, 7% in the entire Imprime group, 17% in the BM+ Imprime group and 0% in the BM- Imprime group. The objective response rate (ORR, all partial responses) was 23% in the control group, 48% in the entire Imprime group (p= 0.048 vs. control), 67% in the BM+ Imprime group (p=0.009 vs. control) and 39% in the BM- Imprime group (p=0.26 vs. control). Among subjects with squamous cell histology, 6 of 6 BM+ Imprime subjects had responses compared with 3 of 10 control subjects (p=0.01). Grade 3/4 adverse events occurred in 25 of 29 control subjects (86%) and 46 of 59 Imprime subjects (78%). All adverse events were consistent with toxicities attributable to the cytotoxic drugs or cetuximab. In summary, the addition of Imprime PGG to chemoimmunotherapy with carboplatin, paclitaxel and cetuximab resulted in improved outcomes in BM+ subjects with respect to increased ORR and extended survival compared to control subjects and had a good safety profile. Citation Format: Michael Thomas, Parvis Sadjadian, Jens Kollmeier, Zhonglin Hao, Myra Patchen, Jamie Lowe, Paulette Mattson, Richard D. Huhn, Nandita Bose, Mary Antonysamy, Michele Gargano, Keith Gordon, Folker Schneller. Imprime PGG improves the efficacy of carboplatin, paclitaxel, and cetuximab chemoimmunotherapy of advanced non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A26.