Viewpoints

An Interview with Dr. Peter Prieto of Iovance Biotherapeutics on TIL Therapy

By Sherrif F. Ibrahim, MD, PhD, FACMS

Interviewee:

Peter A. Prieto, MD, MPH, FACS
Adjunct Professor Surgical Oncology, University of Rochester Medical Center
Senior Vice President, Medical Affairs, Iovance Biotherapeutics, Inc.
CEO & Founder, Prieto Medical, LLC.

On February 16, 2024, Iovance Biotherapeutics received FDA accelerated approval for Amtagvi (lifileucel) for the treatment of unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. This is a first-in-class treatment using a patient’s own tumor infiltrating lymphocytes (TIL) for previously treated advanced melanoma. I had the privilege of speaking with Dr. Prieto about this exciting news.

SI:  Can you tell me a little bit about what Iovance does?

PP:  Iovance is a global leader in innovating, developing and delivering T-cell therapies for solid tumors. We are the only pharmaceutical company to have translated TIL technology out of the research world to a now commercially available treatment. 

SI:  Can you give me an overview of how TIL therapy works?

PP: Amtagvi and our pipeline look at isolating a patient’s own lymphocytes from their tumor and giving them back to the patient in diseases such as metastatic melanoma, non-small cell lung cancer, endometrial cancer, cervical cancer, and head and neck cancers and in the case of melanoma we’ve now been able to scale this up to be able to deliver it across the country and soon to other places in the world.

SI:  How was TIL therapy first developed?

PP:  This technology was pioneered by a surgeon – my former mentor – Dr. Steven A. Rosenberg, who is the chief of the Surgery Branch, National Cancer Institute of the NIH. During my residency at Yale, I was able to work in the lab of Dr. Rosenberg. He taught me that you could cure cancer with the immune system. He was taking metastatic tumors from patients that were told they had weeks to live, isolating the tumor infiltrating lymphocytes, expanding them in the lab (to the billions), and then giving them back to the patient after a preparative lymphodepletion regimen. At the time of infusion and by design these are the only lymphocytes circulating in their bodies.  And he saw response rates that were pretty phenomenal. Our outcomes at Iovance have also been very exciting as evidenced by our label for Amtagvi which is supported by response rates of 31.4%.

SI:  Can you take me through how it works for melanoma? If I am a patient with metastatic disease, how can I get TIL treatment?

PP:  Patients with metastatic melanoma must have first failed traditional systemic immunotherapy (anti-PD1 agents) and if their melanoma harbors the BRAF mutation, they must have also seen targeted therapy. Patients who progress on those agents have no other approved second line systemic therapy. Amtagvi is currently the only FDA approved second line therapy for metastatic melanoma and it is the first-in-class approved T-cell therapy for this challenging disease. So once a patient has failed traditional first line therapies, they would come to an Iovance-authorized treatment center (ATC).

SI:  How does an institution become a treatment center and how many of these centers exist in the nation?

PP: You become an ATC by being authorized by our ATC cell therapy operations team that goes to an institution and leads them through a systematic process and evaluation to ensure that the infrastructure is in place, that providers are experienced with cell therapies (such as CAR-T cells) and making sure that everything is in line with delivering the drug safely. At launch we had 30 centers, and we’ve now increased that number and are on track to have 50 ATCs by the end of this May. We hope to expand to Europe and Canada very soon.

SI:  So everything is done at the site?

PP:  Right. So, at an authorized treatment center, the surgeon takes the patient to the operating room and selects the metastatic lesion that can be resected least invasively. The tumor is then couriered overnight to our state of the art centralized manufacturing facility in Philadelphia where the cells are made. It takes about 22 days to manufacture the cells followed by rigorous quality checks. The patient then goes back to the treatment center for a course of lymphodepletion, which brings their lymphocyte count essentially to zero, followed by infusion of Amtagvi and supportive IL-2.

SI:  It sounds to me almost like a stem cell transplant.

PP: That’s exactly right. The concept is very similar in some ways. It’s a cell transplant of your own tumor infiltrating lymphocytes. 

SI:  How is it different than CAR-T therapy?

PP:  It’s different than CAR-T therapy because in those cases, patients undergo leukophoresis and their lymphocytes are reprogrammed, or genetically modified. TIL by way of Amtagvi are not genetically modified, they come from your own tumor. So there is little to no off-target toxicity, they only go to the tumor. In my opinion, it is THE most personalized form of immunotherapy, it’s your own product.

SI:  How are the TIL’s removed from the tumor?

PP:  They are grown from a proprietary process that was modeled after what was done at the NCI. To support the TIL, patients are also given up to six courses of high dose IL-2 afetr infusion.

SI:  What is the median time to response after TIL infusion?

PP: Based on our clinical trials and pivotal data its about 6 weeks. I will add that you see some really interesting things. We see patients who have gone from a partial response to complete response as late as 3 years, with on-going responses years later. Really impressive results. And remember, they’ve failed as many as 9 other therapies in some cases. So, while not every patient is cured, and not every patient responds, about a third of them do with a meaningful and sustained durability.

SI:  What about transplant patients? Who are not candidates for other immunotherapies?

PP:  If they are not candidates for immune checkpoint immunotherapy, they could be considered for Amtagvi treatment at the practitioner’s’ discretion, although this would be off label. There isn’t an absolute contraindication for these patients for TIL per se, but the Amtagvi label is in the second line.

SI:  How is this process considered a drug?

PP:  It is the most personalized drug made from the patient’s own starting material. By FDA classification it is considered a drug. It gets shipped in up to 4 bags back to the treatment center and can be kept in liquid nitrogen for months until the patient is ready to receive the product.

SI:  What are some future steps that Iovance is looking in to for the treatment of metastatic melanoma?

PP:  While our label is currently approved as second line systemic treatment, we are looking at lifileucel in combination with PD-1 inhibition vs TIL alone as first line therapy with our multinational randomized phase 3 confirmatory trial TILVANCE. Based on the output from this trial our hope is that we can expand to first line therapy.  TIL is a one-time ‘living therapy’. Just like checkpoint inhibitors ten or fifteen years ago, we believe that this is the next chapter in immunotherapy. Melanoma is the beginning, but we are also looking at a variety of other solid tumors.

SI: Absolutely fascinating. Thank you, Peter.

PP: My pleasure.