Ovarian Cancer Moon Shot works to broaden immunotherapy impact
Clayton Boldt, Ph.D.
Immunotherapies have brought the potential for long-term remission and even cures to patients with many cancer types, but the benefits have not yet extended to all patients or all cancer types. Ovarian cancer is one such example.
What’s the current state of using immunotherapy to treat patients with ovarian cancer?
We're still in the very early stages of learning how to best employ immunotherapy for ovarian cancer. Some of the initial single-checkpoint studies are showing benefit in only about 10% to 15% of patients. But there is a lot of interest in using combination immunotherapy and working to better understand the immunosuppressive mechanisms that are particular to ovarian cancer, so we can attack it where it matters. We haven't found a home run and there are no FDA-approved therapies yet, but there is tons of interest and ovarian cancer research in this area.
Are there particular patients who would benefit from new immunotherapy-based approaches?
Many of our clinical trials target what is in some ways the most at-need population within ovarian cancer. Those are patients who develop what's called platinum-resistant or chemo-resistant disease.
Ovarian cancer's natural history is such that early on in the disease, chemotherapies are more effective, and over time the cancer cells become resistant to these treatments. For these patients, really, we're hoping that immunotherapy is going to be the difference maker because other chemotherapies have low benefit rates when the cancer becomes chemo-resistant.
Can you describe some of the Moon Shot’s efforts to investigate new immunotherapy approaches for these patients?
In some ways, immunotherapy has revolutionized cancer care. When you hear that, you think of the patients being treated with immunotherapy, but there’s another way it’s really impacted our understanding of disease.
Evidence suggests that even the effects of chemotherapy may be in part due to immunologically induced cell death. So that’s one of the things that we've been interested in investigating. Through the Moon Shot, we’re leveraging two of our clinical trials that allow us to look at ovarian cancers before and during treatment. These trials use standard chemotherapy, which is carboplatin and taxol, or a combination of carboplatin, taxol and durvalumab, an anti-PD-L1 immune checkpoint inhibitor.
We’re looking at the immunologic effects of chemotherapy alone as well as those of chemotherapy plus immunotherapy. By looking at samples of these two trials in parallel, we'll better understand the impact of chemotherapy and the impact of chemotherapy plus immunotherapy. That's been a major focus of the Moon Shot in upfront ovarian cancer treatment.
We also have a number of clinical trials in the recurrent, platinum-resistant setting. These include approaches that are as diverse as combinations versus sequential use of immune checkpoint inhibitors. We have a trial of intraperitoneally administered immunotherapy.
We also have T cell therapies, including tumor-infiltrating lymphocytes or TILs. This is a type of immunotherapy where immune cells are harvested from a patient’s own tumor samples. The idea is that these are the most relevant T cells, those that have made it to the tumor. In that natural state, there’s too few of them to make a difference. So we grow these T cells in the lab, and patients receive back their own TILs along with a high dose of a growth factor called IL-2 that helps T cells proliferate.
How has the Moon Shots Program® enabled this work?
I don’t think this type of work would really be possible at any other institution. The Moon Shots Program’s exploratory and seemingly unlikely ideas can be tried elsewhere, but may not be supported by typical funding sources or grant mechanisms. Allowing everyone to see the results of their work faster and leveraging those results toward additional funding and clinical trials is really critical. It’s an investment that pays dividends manifold.
The Moon Shots Program has also been a tremendous way to work collaboratively. The TIL program is a great example of multidisciplinary collaboration. This would never be done in just one department. This is a basket trial that includes several cancer types, so we have experts in different diseases as well as a variety of surgical experts. The team that actually treats the patients is in Melanoma Medical Oncology, because they have the greatest experience using TIL therapy. All of this happens in a unit that has extensive experience and can do this as safely as possible. It really is a diverse group of investigators that have come together to offer this to our patients.
What ovarian cancer project are you most excited about now and looking forward?
I am really excited about the intraperitoneal project, especially because of the ability to serially gather cells from the abdominal cavity. Our patients have an intraperitoneal port placed for their treatment, and this allows us to collect cells without an invasive biopsy. We can look at the malignant cells and immune cell populations to get a sense of how they are evolving over the course of treatment.
In the trial I mentioned, patients are being treated every two weeks. That means that every two weeks we can sample the tumor microenvironment, and that’s simply not possible if it required the patient to have an invasive biopsy.
This project gives us the best chance of understanding what obstacles exist to current immunotherapies so that we can come up with more effective approaches for our patients.