Hope Remains for CAR-T Approaches in Ovarian Cancer

Mary “Nora” Disis, MD

This is the second part of a Q&A with Mary “Nora” Disis, MD. For the first part, click here.

Although several clinical trials have evaluated chimeric antigen receptor T-cell (CAR-T) therapies in ovarian cancer, they generally have not met success. As such, some experts have moved on from exploring the potential of CAR-T therapies in this space. On the other hand, there are investigators who continue to see the potential of CAR-T for this indication, especially for patients with high unmet need, like those with advanced stage platinum-resistant ovarian cancer.

Mary “Nora” Disis, MD, director of University of Washington Medicine’s Cancer Vaccine institute, and her colleagues recently shared promising findings regarding PRGN-3005, an investigational MUC16-directed CAR-T therapy that is currently being assessed in patients with advanced stage platinum-resistant ovarian cancer in a phase 1/1b clinical trial (NCT03907527), at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois.

In an interview with CGTLive™’s sister publication OncLive™ held during the conference, Disis spoke about challenges that held back the success of earlier clinical trials applying CAR-T therapies to ovarian cancer and how newer therapies like PRGN-3005 may be able to overcome these challenges. She also discussed the potential of immunotherapy combination treatments to improve outcomes in solid tumors and emphasized the importance of evaluating CAR-T therapies in earlier treatment settings than those typically used in phase 1 trials.

OncLive: Which trends excite you at ASCO's 2023 conference?

Mary “Nora” Disis, MD: I'm really excited to see combination immunotherapy treatments and there's a lot of posters and presentations that are suggesting combination approaches over extended period of time may really benefit the patient in terms of seeing very prolonged disease stabilizations or pushing more patients into remissions. So I'm very excited as people begin to combine immune checkpoint inhibitors with CAR therapy, with cancer vaccines—we're pushing ever closer to really getting the full extent of immune therapies to patients, especially with solid tumors.

Can you speak to the potential use of CAR-T products in ovarian cancer?

CAR T-cell products in the ovarian cancer space have been tested and haven't seemed to be that effective. They were done with first-generation technologies and 1 of the major problems was that they really didn't persist in the body, and so they really didn't have much of an antitumor effect. I think with strategies that are engineering agents to help those CAR T-cell products persist we'll start seeing clinical efficacy with these products in ovarian cancer.

Beyond PRGN-3005, are there any other CAR-T therapies in development that you think might have potential to treat ovarian cancer?

I think people are looking at some of these newer technologies and bringing them to different cancers. I think ovarian cancer has been a little bit of a problem for 2 reasons. Number 1, there were some very early studies that turned out to be negative and that usually drives people away from using that as their first-in-man studies. Then the second thing is people are very curious about what the route of administration should be: intraperitoneal or intravenous? I'm hoping that once this phase 1 study is published, showing some level of efficacy and also addressing those issues of dosing [it] will bring more people working on CAR T-cells back to ovarian cancer because in cisplatin-refractory ovarian cancer we certainly do need many more treatment options.

Can you discuss the importance of disease stage when it comes to CAR-T therapies?

I think any immunotherapy needs to be given earlier in the treatment regimen than what's being done in phase 1 studies. For instance, in our phase 1 study, the majority of the patients had had 6 or 8 lines of treatment prior to getting the CAR T-cell therapy. That's why it was a surprise to be able to see some disease reduction. But if you can see responses in these advanced stage patients it makes sense that when the disease burden is more limited any type of immunotherapy should be able to work better. We certainly have seen that with immune checkpoint inhibitor therapy. So it's my hope that we might see CAR T-cell therapy integrated right after adjuvant therapy or even intermixed with adjuvant therapy, in women who've been optimally debulked, trying to mop up that micrometastatic disease, which is the major problem for patients with ovarian cancer—they have very high risk of relapse. When you think about it, the immune system really is the only way to get down to single-cell kill and we'll be able to do that rapidly with the infusion of tumor-directed CAR T-cells.

Transcript edited for clarity. Click here for more coverage of ASCO 2023.

REFERENCE
1. Liao JB, Stanton SE, Chakiath M, et al. Phase 1/1b study of PRGN-3005 autologous UltraCAR-T cells manufactured overnight for infusion next day to advanced stage platinum resistant ovarian cancer patients. Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #5590