September 26, 2016

SITC 2016: Intralesional injection with Rose Bengal and systemic chemotherapy induces anti-tumor immunity in a murine model of pancreatic cancer

Updated below: 9/26/16 {twice}, 9/28/16 and 9/30/16.

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Updated (9/26/16): According to the Pancreatic Cancer Action Network, there are three chemotherapy drugs approved by the United States Food and Drug Administration (FDA) for the treatment of pancreatic cancer: albumin-bound paclitaxel (ABRAXANE®), gemcitabine (Gemzar®) and fluorouracil (5-FU).
"Gemcitabine (Gemzar®) was approved in 1996 for the treatment of unresectable pancreatic cancer. Studies have also shown that there is a benefit to using gemcitabine after surgery for pancreatic cancer. Prior to gemcitabine, fluorouracil (5-FU) was used as the standard treatment for unresectable pancreatic cancer. Both of these drugs are still used today. 
Most recently, in September 2013, albumin-bound paclitaxel (ABRAXANE®) was approved to be used in combination with gemcitabine (Gemzar®) as first-line treatment for metastatic pancreatic adenocarcinoma, the most common type of pancreatic cancer. 
In addition to the three FDA-approved drugs, FOLFIRINOX, a combination of three chemotherapy drugs (5-FU/leucovorin, irinotecan, and oxaliplatin) is commonly used in the treatment of metastatic pancreatic adenocarcinoma. In 2010, a Phase III clinical trial showed positive results for patients treated with FOLFIRINOX. Due to the results of this study, FOLFIRINOX is also considered a standard treatment option for patients with metastatic pancreatic cancer. However, patients treated with FOLFIRINOX may experience more severe side effects than those treated with gemcitabine alone, so this combination is usually given to patients who are healthy enough to tolerate the potential side effects."
Abraxane is made by Celgene. Gemzar is made by Eli Lilly. Provectus previously showed the combination of 5-FU and PV-10 for hepatocellular carcinoma in murine model work (SITC 2012).

Updated (9/26/16): I believe the systemic chemotherapy used in Moffitt's work is gemcitabine (Gemzar®), which by now is produced by generics manufacturers.

Some recent information on the competitive landscape for pancreatic cancer:
  • "Eli Lilly's chemotherapy drug Gemzar (gemcitabine) is widely considered the standard of care for pancreatic cancer. Generic gemcitabine is available from numerous companies" {January 2014 source},
  • "In the past, companies have combined various targeted treatments with gemcitabine in an attempt to increase their survival benefit. These efforts include Bristol-Myers Squibb/Eli Lilly's Erbitux, Roche's Avastin, Pfizer's Inlyta, and Amgen/Bayer's Nexavar, among others. Unfortunately, none of these drugs has shown a significant survival benefit when combined with gemcitabine" {above source},
    • "Frontline therapies for patients with metastatic pancreatic cancer have advanced in the past 5 years, with the FDA approval of nab-paclitaxel (Abraxane) plus gemcitabine (Gemzar). These advancements branch off the established treatment paradigm of gemcitabine monotherapy, which showed a significant extension in overall survival (OS) compared with 5-FU alone in a phase III study."
  • "Pancreatic cancer is a particularly tough cancer to treat and a number of other companies have failed in their efforts to develop an effective treatment. In February, Incyte halted trials of its drug Jakafi in solid tumors, after a Phase 3 study in pancreatic cancer failed to show efficacy. And this past May saw pancreatic cancer immunotherapies from NewLink Genetics and Aduro Biotech fall short of goal in Phase 3 and Phase 2b trials, respectively" {September 2016 source}, and
  • Momenta Pharmaceuticals has decided to end development of necuparanib, an experimental drug for advanced pancreatic cancer and the biotech's lead clinical candidate, according to a regulatory filing submitted Thursday. Enrollment in a Phase 2 trial testing necuparanib in combination with Celgene's Abraxane was halted earlier this month after an independent data safety monitoring board concluded treatment didn't demonstrate a sufficient level of efficacy {above source}.
Updated (9/28/16): In 2011 co-founder and former Chairman and CEO Dr. Craig Dees, PhD presented Provectus' murine model work examining PV-10's "immunologic potential in treating melanoma and other cancer indications including liver, pancreatic and colorectal cancer." See several pertinent slides below.
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Updated (9/30/16): H/t @bradpalm1: Vitamin D + immunotherapy + chemotherapy..."Physicians and Physicists Join Forces to Fight Pancreatic Cancer," The Wall Street Journal, September 25th, Ron Winslow
"The team is planning a clinical trial soon in which patients who are candidates for pancreatic-cancer surgery first will be treated with synthetic vitamin D, chemotherapy and Bristol-Myers Squibb Co.’s cancer immunotherapy Opdivo. Opdivo is one of the new so-called checkpoint inhibitors that are transforming treatment of cancers such as melanoma and lung cancer. The drugs work by releasing brakes on immune-system T cells, enabling them to pursue tumor cells." 
Bristol-Myers also is combining Opdivo with several other companies and drugs to treat pancreatic cancer, such as Celgene (Abraxane/Paclitaxel protein-bound) and Aduro Biotech (CRS-207 and GVAX)*. Opdivo combination trials for pancreatic cancer on include at least eight studies.

* CRS-207 and GVAX failed as a regimen for pancreatic cancer.

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