A 46 year-old man residing in the Louisville, Kentucky area was given about six months to live, according to a physician’s grim forecast. With stage four lung cancer that August, Tony Burton’s options for life narrowed but he sought out a second opinion with Dr. Jason Chesney at the University of Louisville Health’s James Graham Brown Cancer Center. Thanks to the clinical research as a care movement, a potential advanced but investigational therapy was identified as a potential treatment course for Mr. Burton. Just a couple years ago, the Kentucky resident would have had to travel far to access the same immuno-oncology-based investigational therapy. Tumor infiltrating lymphocytes (TIL), where some of the patient’s tumor is surgically removed while cell-based therapy actually is used in the lab to “reprogram” the patient’s existing cells, which are later reinfused, and unleashed back into the patient to destroy the tumor cells. As it turned out, the physician Burton consulted, Dr. Chesney, also happened to be the principal investigator for this advanced, not-yet-approved FDA approved approach. To date, this procedure has eliminated six of Mr. Burton’s seven tumors. Declaring to local 12 WKRC media, Mr. Burton shared “As of today, I only have one tumor left. I’m hoping at my next scan it will be gone.” This near “game changer” of a treatment has given the patient a second chance look at extending life. This treatment actually fits in a powerful class called immuno-oncology. The specific investigational approach is sponsored by Iovance Biotherapeutics: the company embraced the TIL approach developed at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH).
Huge Promise for Cancer Patients
University of Louisville’s Dr. Jason Chesney recently connected with local media (Local 12 WKRC), commenting that immunotherapy treatments are making a significant impact on cancer care, reducing death by cancer by as much as 25 percent. The Kentucky-based physician and principal investigator suggests a “game changer” such as cell-based therapies could save even another 25 percent.
He declared “I have 10 to 20 patients who have been told to ‘go home and die,” and now they’re living normal life spans without having to receive any treatment.” TrialSite suggests the reader consider this carefully.
A great advancement has already been made and it is still the early inning of a long game. The potential is huge: Cancer patients need to be aware of these studies and the potential for an extension on life.
Bringing Advanced Therapies to All Regions
The cancer research as a care option movement, supported extensively by the NCI, seeks to bring life-saving advance treatments to parts of the country that heretofore patients would have to travel long and far to access. Often considered “underrepresented,” these patients can be far from major urban centers such as New York, Boston, Los Angeles, or Houston. The goal is to bring the cutting-edge cancer treatments to top academic medical centers in regions around the nation to ensure patients far from traditional primary academic medical center hubs have the opportunity to access the same studies.
For example, just a few years ago this advanced immuno-oncology-based investigational therapy targeting “incurable cancers” was only available in major coastal metropolitan areas.
For instance, residents in the Louisville, KY area had to travel all the way to Houston to visit MD Anderson to access this TIL-based investigational therapy. But a couple years ago, the University of Louisville, Kentucky Brown Cancer Center’s embrace of the study ensured that Kentucky was the only “landlocked” state to make this experimental therapy available, reported the university. Of course, this greatly benefits residents in Kentucky and surrounding states making advanced cancer studies more available.
NCI Origins of Treatment
The use of the immuno-oncology-based therapy involving tumor infiltrating lymphocytes (TIL) is actually part of a treatment called adoptive cell therapy or ACT. The TIL approach embraced by Iovance Biotherapeutics was first taken on and further developed by Lion Biotechnologies, which merged in with another biotech venture to form the present day Iovance Biotherapeutics.
As described in the company’s SEC disclosures, the process of adoptive cell therapy (ACT) centers on the autologous tumor infiltrating lymphocytes (TIL) approach invented by Dr. Steven Rosenberg, Chief of Surgery at the National Cancer Institute, a recognized pioneer in immuno-oncology. A timeline for the origins and development of this treatment can be read here.
The Experimental Treatment
Called “Tumor-infiltrating lymphocytes,” this experimental treatment represents the use of a type of white blood cell that has been reprogrammed outside of, and re-infused into the human body. Upon entry, they stimulate the immune system to kill the cancerous tumor.
Dr. Chesney likens the treatment “as a mini version of a bone marrow transplant.” Described as “difficult and painful,” nonetheless early progress shows significant patient benefit while early studies already evidence induced durable remissions.
The actual name for this investigational treatment produced by Iovance Biotherapeutics Inc. is LN-145 or lifileucel. A form of immuno-therapy, the sponsor describes in more detail how this investigational treatment actually works.
In summary, first the patient’s tumor is surgically isolated from the patient and thereafter the sample is shipped to the GMP (FDA compliant good manufacturing process) facility where TIL are isolated and multiplied to generate billions of TIL over three weeks. In parallel the cancer center (trial site organization) prepares the patient with pre-conditioning therapy so the patient can receive the TIL. Finally the investigational TIL product (lifileucel) is administered as a one-time therapy followed up by up to 6 doses of IL-2 to support growth and activation of the TIL therapy inside the patient.
Based on information gathered from the company’s investor presentation, they now run five clinical programs in melanoma, cervical, head & neck, non-small cell lung cancer (NSCLC) and CLL indications.
Clinicaltrials.gov actually lists three clinical trials involving TIL at University of Louisville Brown Cancer Center; one withdrawn, one study (NCT02360579) is active and not recruiting, and one study (NCT03108495) remains actively recruiting patients.
The active and not recruiting study (NCT02360579) is a multicenter prospective, interventional study investigating adoptive cell therapy (ACT) via infusion of LN-145 (autologous TIL) followed by interleukin 2 (IL-2) after a nonmyeloablative lymphodepletion (NMA LD) preconditioning regimen. This latter regimen involves use of chemotherapy.
This latter actively recruiting study (NCT03108495) investigates the use of LN-145, the adoptive cell transfer therapy based on an autologous (done outside of one’s body) TIL manufacturing process for the treatment of patients with recurrent, metastatic, or persistent cervical carcinoma.
A total of eight (8) studies are listed that have involved the intervention LN-145.
About James Graham Brown Cancer Center
The University of Louisville James Graham Brown Cancer Center is a nationally recognized academic cancer center affiliated with the University of Louisville School of Medicine. With a significant national recognition of quality programs, with awards of excellence for clinical care, research, and education, as well as community outreach, this cancer center considers itself one of the top such cancer centers in the nation. It serves a city with about 625,000 residents as well as a greater metropolitan area totaling 1.3 million people.
This center has earned a number of accreditations including the Commission on Cancer, National Accreditation Program for Breast Cancers, American College of Radiology and their Blood and Marrow Transplant Program is nationally accredited by the Foundation for the Accreditation of Cellular Therapy (FACT), the gold standard of excellence for blood and bone marrow transplant programs in the United States. Moreover, Anthem Blue Cross and Blue Shield in Kentucky has recognized the James Graham Brown Cancer Center with a Blue Distinction® Centers for Cancer Care designation as part of the major health insurer’s value-based program involving adult bone marrow and stem cell transplants.
Headquartered in San Carlos, CA (San Francisco Peninsula), Iovance Biotherapeutics, Inc. also has offices in New York and Philadelphia with a research facility in Tampa, Florida, and a commercial manufacturing facility under construction in the navy corporate yard in Philadelphia.
This late-stage biotechnology company centers its effort on the development of novel T cell-based cancer immunotherapies with its primary investigational therapy based on its tumor-infiltrating lymphocyte (TIL) therapy called lifileucel targeting first metastatic melanoma. The company is preparing to submit to the U.S. FDA a Biologics License Application (BLA) and is actively engaged in discussions with the regulatory agency.
As described in a recent investor presentation, the company positions its investors (overwhelming institutional investors) that they are working toward FDA approval which would open up a large market with a great unmet need. If approved in 2021, the company first plans on focusing on post-checkpoint and solid tumor patients and thereafter expands into combinations and earlier lines of therapy.
The company sponsors five clinical programs in melanoma, cervical, head & neck, non-small cell lung cancer (NSCLC) and CLL indications; more details can be reviewed in their investor presentation.
Call to Action: If you or a loved one have a cancer diagnosis, talk to your physician about immuno-oncology approaches and the various advancements ongoing. Feel free to check in with TrialSite if you need help locating studies. If you are based in KY, you can request an appointment with Dr. Chesney here.