As noted in an earlier blog, GVAX is a kind of vaccine that appears to work by enhancing “granulocyte-macrophage colony-stimulating factor” (GM-CSF) which in turn enhances white blood cells including monocytes that can somewhat freely move and have the ability to transform into so-called “professional” antigen-presenting cells such as macrophages and dendritic cells – which can augment the internal immune system’s own ability to fight cancer.
We were alerted to recent GVAX work by David Desert, and want to thank him for this. In an article first presented by electronic release on September 18, 2013, Laheru and colleagues from Johns Hopkins University published work in the Annals of Surgical Oncology that noted a possible relationship between hematologic status and survival in patients with pancreatic cancer who had received treatment with GVAX.
The researchers studied 59 pancreatic cancer patients in an existing Phase II clinical trial who received adjuvant chemoradiation plus GVAX after initial surgery. The Hopkins team found that those who carried a baseline total lymphocyte count of less than 1,500 cells per mm³ were at higher risk of poor overall survival and of progression-free survival. The authors also found that the chemoradiation treatment significantly reduced lymphocyte counts from baseline levels, and that those patients with such suppression to lower than 500 cells per mm³ were also at a disadvantage in terms of overall survival and of progression-free survival.
This is an interesting study that links potential efficacy of treatment (or lack thereof) with immunologic therapy under conditions of immunosuppression. These are early findings with a number of potential confounders, but nonetheless a highly interesting study result.
Dale O’Brien, MD
FDA Grants Orphan Status for CRS-207 (Mesothelin Targeting Vaccine) in Sequence with GVAX Immunotherapy
In an interesting step with intriguingly complex promise, the Office of Orphan Products Development of the U.S. Food and Drug Administration recently designated the immunotherapy CRS-207 as having orphan drug status for use in sequential combination with the GVAX Pancreas biologic for the treatment of pancreatic cancer. Both of these immunotherapeutic agents are owned by Aduro BioTech Inc. of Berkeley, California.
This move by the FDA coincides with Aduro having recently completed a randomized controlled Phase II clinical trial of patients with metastatic pancreatic cancer with this regimen (as yet unpublished), and appears to have sprung from the earlier work of Laheru and colleagues at Johns Hopkins University pursuant to a study published in the February 2012 issue of Clinical Cancer Research, the official journal of the American Association For Cancer Research. In this earlier Phase I research study, three of the patients with pancreatic cancer who had been earlier treated with GVAX appeared to show disease stability after the addition of further immunotherapy that included CRS-207.
Although vaccines and immunotherapies have been an interesting concept in theory generally in cancer and specifically in pancreatic cancer – there have been no clear breakthroughs.
CRS-207 is a live but attenuated Listeria monocytogenes strain that is aimed to induce an immunologic response specific to the antigen: mesothelin – which tends to be over-expressed in pancreatic adenocarcinoma. GVAX is a biologic that stimulates “granulocyte-macrophage colony-stimulating factor” (GM-CSF), boosting white cells including monocytes that roam and can mature into macrophages and dendritic cells – which augment the immune system’s ability to fight cancer.
In February 2013, Aduro purchased GVAX from BioSante Pharmaceuticals, Inc. Drew Pardoll, MD, PhD of Johns Hopkins University is the Chairman of the Scientific Advisory Board of Aduro BioTech. He and other researchers from Johns Hopkins have been involved in research with GVAX and pancreatic cancer for over a decade.
This 1-2 punch (CRS-207 / GVAX) at different areas of the immunologic / inflammatory cascade is a clever and promising idea. It will be interesting to see the results of the Phase II work, and to follow the results of this novel and creative line of study.
Dale O’Brien, MD
Since the promising article on the 4-drug 5-FU led FOLFIRINOX regimen for metastatic pancreatic cancer per the May 12, 2011 article in the New England Journal of Medicine, this treatment approach has emerged as a solid first-line option. In the ensuing months there have been a number of studies exploring further options with this drug combination, including for other stages of cancer of the pancreas.
Now comes interesting research by Wahba and El-Hadaad of Mansoura University, Egypt as published in the September issue of the Journal of Gastrointestinal Cancer looking at a somewhat truncated version of this regimen in patients whose advanced pancreatic cancer showed progression after treatment with gemcitabine.
In a phase 2 clinical trial, the authors treated thirty such patients with a regimen that included 5-FU (fluorouacil), folinic acid, and oxaliplatin (the FOLFIRINOX regimen without irinotecan) with tolerable (adjudged) side-effects and a median overall survival of 22 weeks, and a six-month survival rate of 30%. They conclude that this regimen is active and in need of further study.
We concur. Very interesting work – that would benefit by follow-up research.
Dale O’Brien, MD