The oncology world’s version of a “smart bomb” is well underway.
While traditional treatments such as chemotherapy or radiation target active cancer cells in a physical region, new procedures are waging an extremely precise war against specific proteins and molecules involved in cancer growth.
The cancer world’s smart bomb comes in the form of an immunotoxin. Immunotoxins carry a payload of chemotherapy and attach to the cancerous cell, killing it when the time is right.
An immunotoxin is an antibody combined with a toxin. The antibody seeks out and attaches itself to a cancer cell — the cancer cell allows it because it does not initially perceive the antibody as a threat. The antibody unlocks the cell and releases a deadly toxin inside. The toxin kills the cancerous cell.
Nicholas Vogelzang
Immunotoxins are different than immunotherapy, or immuno-oncology, which is another form of targeted therapy. Immuno-oncology therapies boost the body’s immune system to attack cancer cells.
One targeted therapy, developed in part by Comprehensive Cancer Centers of Nevada, is the anti-PDL1 compound MPDL3280A. This therapy was proven to be effective in combatting a number of different cancers containing the PDL1 protein, including melanoma, kidney, bladder, head and neck as well as breast cancers. The anti-PDL1 therapy was fully approved by the Food and Drug Administration in October 2014.
Edwin Kingsley
Targeted therapy such as anti-PDL1 and immunotoxins can come with less severe and minimalized side effects, as treatments focus on specific molecules and not all metastasizing and/or cancerous cells throughout the body. Side effects from using immunotoxins are typically very mild – some patients may experience a mild reaction such as a rash, low blood pressure or swelling in targeted areas. Additionally, collateral damage to surrounding, otherwise healthy cells is reduced.
A first in the U.S., right here in Nevada
Recently, CCCN became the first site in the country to open a very promising Phase I immunotoxin drug trial. The drug being tested, SGN-CD70, targets a specific protein found in lymphoma and kidney cancers known as CD70.
The SGN-CD70 drug is a first-in-class drug and is the only drug on the market targeting the CD70 protein. SGN-CD70 is an immunotoxin designed and engineered to identify and attach to the CD70 protein, which is found on the cell surface of some high-grade lymphomas and kidney cancers.
CCCN was directly approached by Seattle Genetics to spearhead the SGN-CD70 trial, thanks to its recent clinical successes in the lymphoma realm, and remains one of the very few sites across the country to have it open. CCCN is granted access to more than 170 clinical trials each year, in large part due to its affiliations with the U.S. Oncology Network and Jonsson Comprehensive Cancer Center at UCLA.
Before a treatment achieves FDA approval, it must be tested. The SGN-CD70 trial is in Phase I, meaning the immunotoxin has been pre-clinically studied in test tubes as well as animals and there is significant evidence suggesting it will work in human beings. This Phase I trial marks the first time the drug has been administered in humans — now is the time to determine which tumors it will work in, the safety of a range of doses and toxicity in humans.
In the oncology world, the goal is always to hit a home run in Phase I trials – once efficacy, dosage and toxicity are determined, the trial can potentially move through to Phase II (detailing the safety of a treatment), Phase III (comparing a drug to most effective treatments available) and Phase IV (testing a drug once it has been approved by the FDA). To date, CCCN has played a role in developing 52 FDA-approved cancer therapies and hopes to add to its successes with this trial.
There has been notable patient success with immunotoxin drugs and trials similar to SGN-CD70, one example being the drug Ontak, which is also known by its generic name Denileukin Diftitox. Ontak is used in the treatment of recurrent T-cell lymphoma for patients who have a high-rate of the CD-25 protein and is typically administered intravenously. The drug was originally approved by the FDA in 1999 and has since helped countless patients across the globe.
Before the SGN-CD70 drug can potentially make its way through the phases and impact lives in an Ontak-like fashion, there must be a strong base of Phase I patients.
Wanted: patients
So, who is the optimal patient for the SGN-CD70 trial? First and foremost a prospective patient must have the CD70 protein present. A simple test at a local CCCN clinic can verify the eligibility requirements.
During these beginning stages of the SGN-CD70 trial, CCCN is solely seeking lymphoma patients, specifically those with an aggressive form of non-Hodgkins lymphoma.
The majority of Phase I patients are those who have had their respective disease for a while and/or have received multiple treatments without lasting success. One advantage of this drug is that it can be given to patients who have other health issues, and it will have a minimal impact on their overall vitality.
CCCN remains the only center in Nevada conducting Phase I research. Specifically for local patients who have struggled to find the right treatment, this trial provides a significant and convenient opportunity in our backyard.
Another step forward in treating kidney cancer
On the spectrum of cancer treatment, lymphoma is traditionally easier to treat than kidney cancer. Once an appropriate dosage is identified for lymphoma patients, the trial will be subsequently opened up to kidney cancer patients.
The advances in kidney cancer in recent years have been nothing short of astounding. Today, the average person whose cancer metastasizes lives an approximate 2 1/2 to more than three years. Before modern medicine, these patients lived approximately nine months – thus, the quality and length of life has greatly improved overall.
Kidney cancer remains such an attractive target for clinical trials because the cancer is very unique, has the potential to go into remission and also has the potential to be recalcitrant through therapy. Amid the improvements, there are still younger cancer patients, in their 40s and 50s, who are still seeking the right treatment that will work for them. For kidney cancer patients, this specific drug is shaping up to be quite promising.
It is a novel-agent that has the capacity to hit kidney tumors in a way that they have not been hit before – attacking the CD70 protein, which is expressed in the majority of kidney cancer patients. Now that we have the drug and a novel way to target the CD70 molecule, it is an exciting, prospective new chapter for kidney cancer patients.
Currently, there are only a handful of patients in the world enrolled in the SGN-CD70 study. As more qualifying patients enroll in the lymphoma portion of the study, the kidney cancer trials will become more of a reality – potentially as early as the second quarter of 2015.
Through targeted therapies, such as the SGN-CD70 trial, cancer is being combatted in a sophisticated and strategic fashion. In addition to providing improved health and quality of life to patients who have otherwise exhausted all other treatment options, these trials are also providing a new level of hope to all of those touched by cancer.
Dr. Edwin Kingsley is a veteran of medical oncology and hematology in Las Vegas and is one of the co-founders of Comprehensive Cancer Centers of Nevada. He is the principal investigator of multiple clinical trials at the practice and the author of nine publications. He is an adjunct assistant clinical professor at Touro University, a past president of the Nevada State Medical Association as well as the Clark County Medical Society and an active investigator for the Southern Nevada Community Clinical Oncology Program.
Dr. Nicholas Vogelzang is a medical oncologist at Comprehensive Cancer Centers of Nevada and serves as medical director of the Research Executive Committee, associate chair of the Developmental Therapeutics Committee, and member of the Genitourinary Committee for US Oncology Research.
In his roles, he leads cutting-edge clinical trials in genitourinary malignancies and mesothelioma, and is involved in new therapies for patients with metastatic kidney cancer, including gene therapy and cytokine therapy.