A new clinical trial through the Mesothelioma Center at the Baylor College of Medicine Lung Institute will be testing a new combination therapy as a second-line treatment for pleural mesothelioma. The phase 2 trial is combining the immunotherapy drug nivolumab with a new agent called MTG201 developed by Momotaro-Gene Inc. in Japan, in hopes of ultimately extending survival. After promising responses in a phase 1 trial with MTG201, which took place over the course of about two years, researchers at Baylor College of Medicine hope to see positive treatment-related responses in this next phase of study.
Dr. Bryan Burt, Associate Professor of Surgery at Baylor College of Medicine and member of the Dan L Duncan Comprehensive Cancer Center at Baylor, recently spoke with Mesothelioma.com about the upcoming clinical trial.
Combining MTG201 with Nivolumab
Mesothelioma research has long been focused on finding a viable second-line treatment for patients who experience disease progression or recurrence after treatment with standard therapy. The recruiting clinical trial at Baylor is available for pleural mesothelioma patients who have previously undergone chemotherapy and seen disease progression.
“After first-line standard chemotherapy, patients move onto the second-line if the disease progresses after chemotherapy,” Dr. Burt explained. “This trial is a treatment trial for patients with mesothelioma in which they are treated with a combination of two drugs. One drug, nivolumab, has become a standard immunotherapy drug for a number of malignancies, including lung cancer, and these classes of immunotherapy drugs are recommended for mesothelioma patients in the second-line.”
Immunotherapy drugs work by boosting the patient’s immune system to recognize and kill the cancer cells. Nivolumab is a PD-1 inhibitor, meaning the drug works by blocking the negative interaction of the PD-L1 protein, which can be found on normal and cancer cells, with the PD-1 receptor on T cells. With the presence of the PD-L1 protein, the cancer cells trick the immune system into thinking they are healthy, normal cells. By blocking the protein signal, cancer cells can be recognized by the T cells in the immune system, thus preventing them from growing and spreading.
“Our trial uses this immunotherapy drug in combination with the new agent, MTG201,” Dr. Burt continued. “It’s an adenovirus-based therapeutic that accelerates cell death in cancer cells. By doing that, it releases the contents of the cancer cells, including antigens that the immune system can potentially recognize that weren’t available before. This, we believe, may be one mechanism that provides the immunotherapy with an opportunity to be more effective.”
A Look at the Phase 1 Trial
The combination therapy of nivolumab with MTG201 is able to move into a phase 2 clinical trial because of the results from a phase 1 trial in Japan.
“This is a phase 2 trial because it has been tested in other human tumors before, including mesothelioma and prostate cancer,” Dr. Burt told Mesothelioma.com. “The MTG201 was shown to be well tolerated when delivered in the pleural space of patients with mesothelioma and there were also some objective responses noted. Our current trial is the first in which MTG201 will be combined with immunotherapy in patients with mesothelioma.”
The researchers feel confident moving forward with the combination treatment because of how the therapy worked in a mouse model. Dr. Burt’s laboratory found that the two drugs eradicate mouse mesothelioma tumors consistently and rapidly.
Researchers Hope for Continued Positive Results
In the phase 2 study, Dr. Burt and his team are looking to see if the treatment will shrink tumors. Ultimately, they hope to see the treatment extend survival for patients.
If patients are interested in participating in the clinical trial at Baylor, they should discuss the option with their medical team. Patients who want to participate will have to travel to Baylor College of Medicine for treatment, as it is currently the only center testing the treatment combination. The study will include patients with any stage of pleural mesothelioma and any cell type.
Patients who have not previously undergone mesothelioma treatment, however, are not eligible. The trial is only accepting patients who have previously been treated with chemotherapy or surgery and seen growth or recurrence following treatment. Detailed information for this study can be found at clinicaltrials.gov NCT04013334.
Once the trial gets underway, Dr. Burt anticipates it will run for one to two years. If the researchers see promising results like in phase 1, the combination therapy would likely continue to be studied in additional clinical trials.
“The next step would be to make this available to more patients, potentially in a larger randomized trial involving multiple institutions,” Dr. Burt said. “We are currently working on understanding the mechanism by which this combination works in preclinical studies and the biomarker component of our trials will facilitate the understanding in humans.”