ASCO: Biothera to present phase 2 study data on predictive serum biomarker for NSCLC

Biothera will present research at the American Society of Clinical Oncology (ASCO) annual meeting linking a potential predictive serum biomarker to the clinical response to Imprime PGG^® immunotherapy in a recent phase 2 study in non-small cell lung cancer patients. The meeting begins today and runs through June 3 in Chicago. 

Biothera's Imprime PGG is a yeast-derived, soluble β-glucan that primes innate immune cells such as neutrophils and macrophages to kill antibody-targeted cancer cells via a complement receptor 3 (CR3)-dependent mechanism. In humans, naturally occurring anti-β-glucan antibodies (ABA) are required for binding of Imprime PGG to CR3 and subsequent activation of innate immune cells.

In a study of healthy volunteers, serum ABA levels above a threshold cutoff level were predictive of higher neutrophil binding of Imprime PGG as well as enhanced functional activities, including complement activation, complement receptor expression, activation marker modulation, and selective chemokine production.

The potential of serum ABA levels as a biomarker for clinical response to Imprime PGG was subsequently evaluated in a Phase 2 clinical trial by retrospectively segregating subjects into populations at or above the independently established ABA threshold (biomarker positive; BM+) or below the ABA threshold (biomarker negative; BM-).

In this randomized, phase 2 study, stage IV NSCLC patients received cetuximab, carboplatin and paclitaxel without (Control) or with Imprime PGG 4 mg/kg on Days 1, 8 and 15 of each 3-week treatment cycle for the first 4 to 6 cycles. Maintenance treatment with cetuximab alone or in combination with Imprime PGG was continued until disease progression.

Overall, the objective response rate (ORR; primary endpoint) was 23% in the control group (6/26), and 48% in the Imprime PGG group (22/46;>

"In NSCLC patients, the addition of Imprime PGG to carboplatin, paclitaxel and cetuximab therapy resulted in significantly improved objective response rate," said Ada Braun, M.D., Ph.D., Biothera chief medical officer. "In patients with ABA levels above the pre-specified threshold cutoff, the objective response rate nearly tripled compared to control and there was a trend for improved survival."

Median overall survival was 11.3 months in the control group, 12.4 months in the entire Imprime PGG group.

Serum ABA levels may be a predictive biomarker for Imprime PGG activity. Further research to characterize the predictive significance of the biomarker is ongoing.

"Establishment of a predictive biomarker for Imprime PGG will enable the enrichment of future clinical trials and, ultimately, provide oncologists with additional tools for evaluating treatment options for their patients," said Dan Conners, president of Biothera's Pharmaceutical Group.

Biothera ASCO Presentation Details
Biothera's presentation will be part of the general poster session on Developmental Therapeutics - Immunotherapy. The presentation is scheduled for 8:00-11:45 am on Monday, June 1 in McCormick Place, S Hall A2. The Biothera presentation is #112 and entitled, "Endogenous Anti-β-Glucan Antibodies as a Potential Predictive Biomarker for Clinical Response to Imprime PGG Immunotherapy in Non-Small Cell Lung Cancer (NSCLC) Patients." Abstract ID: 3045.

The research is a collaboration of Biothera and:

• Thoraxklinik, University of Heidelberg, Translational Lung Research Center Heidelberg, Heidelberg, Germany.
• Johannes Wesling Klinikum Minden, Minden, Germany.
• Policlinic of the Klinikum rechts der Isar, Technical University Munich, Muenchen, Germany.

Source Biothera