Biothera today reported positive results from its proof of concept Phase
2 clinical trial in 90 patients with advanced non-small cell lung cancer
(NSCLC) at the American
Association for Cancer Research and the International Association for
the Study of Lung Cancer joint conference on the Molecular Origins of
Lung Cancer in San Diego.
The purpose of the open label, multicenter, randomized trial was to
evaluate the safety and effectiveness of Biothera’s immunotherapeutic
drug candidate, Imprime PGG®, with cetuximab (Erbitux®),
carboplatin and paclitaxel compared with the monoclonal antibody and
chemotherapy combination alone in previously untreated patients with
advanced NSCLC. The primary endpoint of the study was Objective Response
Rate and a secondary endpoint was Overall Survival.
“We believe that combination therapies with Imprime PGG may
significantly increase survival rates for many cancers, including the
most difficult to treat like lung cancer and colorectal cancer, without
adding to the toxicity of the backbone therapy,” said Dan Conners,
president of Biothera’s Pharmaceutical Group. “The opportunity to
provide an effective immunotherapy with overall survival benefits for
squamous cell NSCLC patients, a clinically unmet need, is very exciting.”
Study Results
The combination of Imprime PGG with cetuximab
and carboplatin/paclitaxel showed a substantial and statistically
significant improvement in objective response rate (ORR) of 48%
(p=0.048) in the Imprime PGG treated group compared to 23% in the
control group. This improvement was even greater in the
biomarker-positive subgroup, which had an ORR of 67% (p=0.009).
Beneficial effects were observed in both squamous and non-squamous NSCLC
patients. Among patients with squamous cell NSCLC, a cancer for which
there few treatment options today, the ORR was 100% (N=6) for
biomarker-positive Imprime PGG subjects compared with 30% (N=10) for
control group subjects (p=0.01).
Biothera researchers discovered a predictive biomarker that identifies
patients who are most likely to best respond to Imprime PGG, a patented,
complex carbohydrate (a beta glucan) derived from the cell walls of a
proprietary strain of yeast. The biomarker is a naturally occurring
antibody to beta glucan that is required for binding Imprime PGG to
neutrophils and monocytes, the largest population of immune cells in the
body. When bound, Imprime PGG engages and directs these innate immune
cells to recognize and kill antibody-targeted cancer cells. Using a
serum-based assay, Biothera is able to identify biomarker-positive
patients.
Although the study was not powered for Overall Survival, the results
indicated a strong trend for improvement in the biomarker-positive
subgroup as well. The Median Overall Survival for the biomarker-positive
Imprime PGG-treated subgroup was 16.5 months compared with the control
group of 11.2 months. Positive survival benefits were also observed in
squamous cell as well as non-squamous cell NSCLC patients.
Imprime PGG was well tolerated, with adverse events consistent with
toxicities attributable to the cytotoxic drugs or cetuximab alone.
“Numerous preclinical studies have demonstrated the effectiveness of the
combination therapy of Imprime PGG and monoclonal antibodies in multiple
tumor models. The current clinical data confirm the preclinical results
and validate Biothera’s approach of modulating the innate immune system
to fight virtually all types of cancer,” said Myra Patchen, Ph.D., chief
scientific officer, Biothera’s Pharmaceutical Group. “The excitement
about the biomarker is that it links directly to the mechanism of action
of Imprime PGG and now we have clinical data supporting its use. This
discovery will enable future clinical trials to be enriched for subjects
most likely to respond to Imprime PGG.”
The title of AACR-IASLC poster presentation was “Imprime
PGG improves the efficacy of carboplatin, paclitaxel and cetuximab
chemoimmunotherapy of advanced non-small cell lung cancer (NSCLC).”
This study was conducted at 12 locations in the U.S. and Germany. This
poster was authored by Michael Thomas M.D., Parvis Sadjadian M.D., Jens
Kollmeier M.D., Zhonglin Hao M.D., Nandita Bose Ph.D., Mary Antonysamy
Ph.D., Myra Patchen Ph.D., Jamie Lowe, Michelle Gargano, Richard D. Huhn
M.D., Keith Gorden, Paulette Mattson, Folker Schneller M.D.
About Imprime PGG®
Imprime PGG is a novel immunomodulatory
drug in development as a cancer therapy. Innate immune cells are the
most abundant immune cells in the body and are normally responsible for
pathogen killing, but not anti-tumor activity. However, Imprime PGG has
been shown to bind to neutrophils and monocytes and redirect their
killing ability to reduce tumor growth and enhance long-term survival.
This targeted mechanism is synergistic with multiple anti-tumor
monoclonal antibodies, providing the potential to improve patient
outcomes in a wide range of cancer indications. Imprime PGG has
demonstrated marked improvements in overall response rates in multiple
clinical trials for colorectal
cancer, KRAS-mutant
colorectal cancer and chronic
lymphocytic leukemia. Imprime PGG is currently in a Phase
3 clinical trial for advanced colorectal cancer and a Phase
2 NSCLC study with bevacizumab (Avastin®).
For more information, visit our website at www.biothera.com/pharma.
About Biothera, the Immune Health Company
Biothera is a U.S.
biotechnology company dedicated to improving immune health. The company
is developing pharmaceuticals that engage the innate immune system to
fight cancer.
Copyright Business Wire 2014