Emerging Therapies for Mesothelioma: CAR T-Cell, Gene Therapy, and Tumor Treating Fields

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• CAR T-Cell Therapy for Mesothelioma
• Gene Therapy in Mesothelioma Treatment
• Tumor Treating Fields (TT Fields) Application
• Clinical Trial Advances and Evidence
• Future of Mesothelioma Treatment Landscape
• Full Transcript

CAR T-Cell Therapy for Mesothelioma

CAR T-cell therapy represents an exciting frontier in mesothelioma treatment. Dr. Dean Fennell, MD, highlights promising early data from Memorial Sloan Kettering Cancer Center. This innovative approach targets the mesothelin antigen, which is highly expressed in mesothelioma tumors.

The therapy involves genetically engineering a patient's own T-cells to recognize and attack cancer cells. Dr. Dean Fennell, MD, notes that combining CAR T-cell therapy with immune checkpoint inhibitors may enhance T-cell activity. However, he emphasizes that quality phase 2 efficacy data is needed to establish this as a standard treatment approach.

Gene Therapy in Mesothelioma Treatment

Gene therapy approaches are advancing rapidly in mesothelioma research. Dr. Dean Fennell, MD, discusses the INFINITE study, a randomized phase 3 clinical trial. This trial uses a viral vector delivery system developed by East Coast scientists to transport cytokines directly to mesothelioma tumors.

The therapy specifically delivers GM-CSF to augment immune infiltration of mesothelioma. Dr. Dean Fennell, MD, explains that earlier studies showed promising activity with this approach. The current phase 3 trial combines this viral delivery system with gemcitabine chemotherapy. Positive results could make this the first routinely used gene therapy for mesothelioma patients.

Tumor Treating Fields (TT Fields) Application

Tumor Treating Fields represent a novel non-invasive treatment technology for mesothelioma. Dr. Dean Fennell, MD, explains that TT Fields received FDA approval based on a single-arm phase 2 study. This treatment involves using electric fields to disrupt cancer cell division while sparing healthy cells.

The approval was based on survival data showing approximately 12.5 months in mesothelioma patients. Dr. Dean Fennell, MD, notes that this survival duration appeared significantly better than historical controls from 2003. However, he acknowledges that many experts call for randomized data to determine the true magnitude of benefit from TT Fields in modern treatment contexts.

Clinical Trial Advances and Evidence

Robust clinical trial data remains crucial for advancing mesothelioma treatments. Dr. Dean Fennell, MD, emphasizes the importance of randomized studies for proper treatment evaluation. He references the CONFIRM clinical trial that demonstrated immunotherapy benefits in relapsed mesothelioma.

Dr. Dean Fennell, MD, explains that survival outcomes have improved over the past 17 years due to multiple treatment advances. He cautions against comparing single-arm study results with historical data from different eras. The interview with Dr. Anton Titov, MD, highlights how combination approaches and repeat chemotherapy challenges can provide real patient benefits.

Future of Mesothelioma Treatment Landscape

The mesothelioma treatment landscape continues to evolve with multiple emerging technologies. Dr. Dean Fennell, MD, expresses optimism about CAR T-cell therapy, gene therapy, and Tumor Treating Fields. Each approach offers unique mechanisms of action against this aggressive cancer.

Dr. Dean Fennell, MD, emphasizes that these innovations represent complementary strategies rather than competing treatments. The combination of traditional chemotherapy with novel approaches like viral vector gene delivery shows particular promise. As Dr. Anton Titov, MD, discusses with Dr. Fennell, the field is moving toward personalized combination therapies tailored to individual patient profiles and tumor characteristics.

Full Transcript

Dr. Anton Titov, MD: There is a chimeric antigen receptor T, CAR-T therapy. It has influenced outcomes in a lot of cancers. Can CAR-T therapy be applied in mesothelioma?

Dr. Dean Fennell, MD: We've seen some exciting data from CAR-T therapy, particularly from the Memorial Sloan Kettering Cancer Center in New York. I think it's very early days. Certainly, there is a potential for targeting an antigen called mesothelin, which is highly expressed within mesothelioma.

Mesothelin does lend itself to this type of adoptive T-cell therapy (CAR-T). I have to say at the present time, whether you use a single agent or you combine it with an immune checkpoint inhibitor to augment the T-cell activity, it is unclear. We really have to await that quality phase 2 efficacy data to establish whether this is a new way forward for patients with mesothelioma.

But yes, amongst many other treatments that are out there, I think CAR-T is an exciting opportunity.

Dr. Anton Titov, MD: What about gene therapy? Again, considering how aggressive the nature of mesothelioma is, gene therapy has had its ups and downs throughout the years for different applications. How do you see the gene therapy potential in mesothelioma treatment?

Dr. Dean Fennell, MD: I think we're about as close as we possibly can be towards getting an answer to that question. There is a study called the INFINITE study. It is a randomized phase three clinical trial.

It is using a discovery from scientists from the East Coast of the US who have developed a viral vector that can deliver cytokines, GM-CSF, to augment immune infiltration of the mesothelioma. We can review this clinical study design. We can actually look at the synergistic interaction between chemotherapy alone with gemcitabine combined with this viral delivery system.

This is a phase 3 study because earlier studies had shown very promising activity. My hope is that we will see the results of this study. If the results are positive, this could be the first example of gene therapy becoming used routinely within mesothelioma.

So we're just waiting for the gene therapy results. I think that's the key thing in mesothelioma gene therapy.

Dr. Anton Titov, MD: For some aggressive tumors, glioblastomas for example, there is a non-medical treatment that is being applied now. It's called Tumor Treating Fields, TTF. And that has also been tried for mesothelioma treatment. Is that an additional opportunity? Or is it just trying to apply different technology to any tumor that can potentially be influenced by it?

Dr. Dean Fennell, MD: The Tumor Treating Fields are very intriguing. It is based on a single-arm phase two study of the use of the TTF fields in combination with standard chemotherapy. TTF was accepted by the regulatory agency, the FDA, as an approved treatment for mesothelioma.

This was based on the presumption of survival about 12 and a half months in patients with mesothelioma. That was based on the original publication from 2003. There's no licensing data that was out there.

Seeing a survival that was significantly greater than that in the single-arm Phase two study was the hypothesis that was tested. It was confirmed as being positive. Therefore, the regulatory authorities approved tumor treating fields, TTF, which is fantastic.

I think, however, that many have called for randomized data to determine what the magnitude of benefit for TTF is in mesothelioma. We know that survival has pushed upward over the last number of years. It is partly due to the increasing numbers of treatment options.

I've mentioned the CONFIRM clinical trial, for example, in the relapse of mesothelioma. Immunotherapy may have been used. We know over the last 17 years that the repeat tumor challenge with chemotherapy can, for some patients, confer some real benefits.

Therefore, is it right to look at the overall survival in the single-arm study 10 years later? Maybe Tumor Treating Fields is the real deal. I suspect, certainly from the data associated with TT Fields, that something very important could be happening that's pushed out that survival to the duration that it has.

But the traditional approach, certainly in European approvals, is actually to have some form of randomization. But yes, it is a very interesting, perhaps under-discussed, new technology that's emerged recently and is now licensed for therapy.