An Open-label, Randomized Phase IIB/III Active Control Study of Second-line Hyper-Acute(R)-Lung (Tergenpumatucel-L) Immunotherapy Versus Docetaxel in Progressive or Relapsed Non-Small Cell Lung Cancer
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death in men and
women in the United States. Despite advances in the treatment of advanced NSCLC in the last
decade, survival outcomes remain poor. Treatment benefit from cytotoxic chemotherapy has
reached a plateau and further progress will depend upon identifying novel methods to target
tumor cells.
Harnessing the human immune system to target lung cancer could result in the development of
effective treatment options against lung cancer and potentially enhance the effect of
cytotoxic chemotherapy. Lung cancer cells produce a number of abnormal proteins or abnormal
amounts of certain proteins found in normal lung cells. In some cancers, the abnormal
protein expression may lead to an immune response against the cancer cells much in the way
the immune system responds to an infection. In progressive lung cancer however, the immune
system fails to identify or respond to these abnormalities and the cancer cells are not
attacked or destroyed for reasons not yet fully understood. This clinical trial proposes a
novel method to stimulate the immune system to recognize the abnormal components found in
lung cancer cells and to stimulate an immune response that destroys or blocks the growth of
the cancer.
This new method of treatment helps the immune system of lung cancer patients to "identify"
and target the cancerous tissue. As an example, patients who receive an organ transplant to
replace a damaged kidney or heart are treated with special drugs to supress their immune
response from destroying or "rejecting" the transplanted organ. This "rejection" occurs when
the patient's immune system responds to differences between the cells of the transplanted
organ and their own immune system by attacking the foreign tissue in the same way as it
would attack infected tissue. When the differences between foreign tissues and the patient's
body are even larger, perhaps like differences between organs from pigs and the immune
system cells of humans, the rejection is very rapid, highly destructive and the immunity it
generates is long-lasting. This is called hyperacute rejection and the medicine used to
immunize patients in this protocol tries to harness this response to teach a patient's
immune system to fight their lung cancer just as the body would learn to reject a
transplanted organ from an animal.
To do this, we have placed a mouse gene into cultured human lung cancer cell lines. These
cells will express a sugar that will stimulate a strong immune response in humans. These
cancer cells are irradiated to prevent any growth and then injected along with chemotherapy
to patients with lung cancer. The presence of the sugar will stimulate the patient's immune
system to kill the injected immunotherapy cells. As part of the process of destroying the
immunotherapy cells, the patient's immune system is stimulated to identify as many
differences between these cancer cells and normal human cells. This extra stimulation is
thought to encourage immune responses against the lung cancer in the patient based on shared
abnormalities of lung cancer immunotherapy cells and the patient's lung cancer cells.
In this experimental therapy, patients are given docetaxel or injections of an immunotherapy
consisting of three types of modified lung cancer cells. We propose to test these treatments
in patients with lung cancer who have progressed after initial chemotherapy to demonstrate
that treatment of immunotherapy results in improved tumor stabilization or response and
could potentially improve the patient's overall survival.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall survival
The primary objective in Phase IIB and Phase III is to assess overall survival of anti-tumor immunization using HyperAcute®-Lung (HAL) Immunotherapy versus docetaxel in patients with progressed or relapsed non-small cell lung cancer (NSCLC) that have been previously treated.
Approximately 19 months, assuming a 24 month enrollment.
No
Nicholas N Vahanian, MD
Study Director
NewLink Genetics Corporation
United States: Food and Drug Administration
NLG0301
NCT01774578
January 2013
July 2015
Name | Location |
---|---|
Washington University School of Medicine | Saint Louis, Missouri 63110 |
University of Cincinnati | Cincinnati, Ohio 45267-0502 |
University of Tennessee Medical Center | Knoxville, Tennessee 37920 |