Current and Emerging Therapies for Platinum-Resistant Ovarian Cancer

At the 2022 Great Debates & Updates in Women’s Oncology virtual meeting, Kathleen Moore, MD, Stephenson Cancer Center, Oklahoma City, Oklahoma, gives an overview on recent developments in first-line treatments for advanced stage ovarian cancer.

In her presentation, Dr Moore discussed the current landscape for platinum-resistant ovarian cancer, such as chemotherapy options, as well as novel mechanisms including antibody drug conjugates, cell signaling, and targeted therapies.

Transcript

Hello, I'm Dr. Kathleen Moore. I am a professor of gynecologic oncology, and I serve as the Associate Director of Clinical Research and Director of Phase 1 Clinical Trials at the Stephenson Cancer Center in Oklahoma City. It is my great pleasure to give this short overview of a recent presentation entitled New and Emerging Targets in Platinum Resistant Ovarian Cancer.

When we think about advanced ovarian cancer, there have been some exciting developments in the treatment of frontline advanced stage ovarian cancer, in terms of the addition of PARP inhibitors, with or without bevacizumab. We'll see readout in 2023 of some completed studies with those combinations plus immunotherapy to see if that adds to the frontline armamentarium. We hope that converts more of our patients into the fraction who are cured.

The reality is, even if we do that, we still have many women who will recur from their ovarian cancer, and we will have used some of our best agents already upfront. Once they recur, and they're still platinum-sensitive, this is one big area of development. We still have the use of multiple platinum-doublet backbones with or without bevacizumab. And there are ongoing studies here, as well, for adding immunotherapy and PARP inhibitor therapy in that setting. We'll see those readouts, again, coming up in 2023 and 2024 to see if that area shifts.

Once tumors become resistant or refractory to platinum, this is where there is a high unmet need. If you look at the contemporary studies that have been done in the platinum-resistant space, and you look at the control arms, the overall response rates range from 4% to 13% for commonly used medications such as pegylated liposomal doxorubicin, topotecan, weekly paclitaxel, or gemcitabine. Weekly paclitaxel may be more effective than these others, at maybe 27% response rate. These are the best we have currently in our armamentarium for the platinum-resistant space.

There is a high unmet need in this area, as well as a lot of drug development. Novel targets such as antibody drug conjugates, cell signaling, and targeted therapies such as GAS6/AXL signaling with better accept, and to anti-angiogenesis signaling with the upcoming navicixizumab trial. Then a whole series of trials looking at either novel combinations of immune checkpoint inhibitors or novel immune-stimulating agents such as nemvaukin alfae, and we're seeing engineered T-cell therapy and T-cell receptor engagers, as well. A very exciting time with the number of trials that are ongoing.

The treatment that's closest to the bullseye in terms of hitting and hopefully getting an FDA approval is the antibody drug conjugate mirvetuximab soravtansine. This is an antibody drug conjugate that targets folate receptor alpha. It has a completed single-arm, phase 3 study, which was called SORAYA, with a response rate of 32% and a duration of response of 7 months. We are awaiting the FDA's decision on that accelerated approval application right now. The confirmatory trial is MIRASOL, which we expect a readout and hopefully a confirmed approval in first quarter of 2023.

[EDITOR’S NOTE: As of 11/14/2022, the FDA granted accelerated approval to mirvetuximab soravtansine for FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. To read more about the approval, click here.]

The antibody drug conjugate next in line is upifitamab rilsodotin, which targets the sodium-dependent phosphate transporter as a target. We call this NaPi2b. This also has an accelerated approval run study called UPLIFT, with a confirmatory trial called UP-NEXT, being led by Dr Debra Richardson [MD, Stephenson Cancer Center]. There are also a whole series of these antibody drug conjugates that are all in development and quite exciting. These are just what's most proximal to potentially reading out.

Other exciting opportunities that will also readout in 2023 is the Novocure technology in tumor treating fields, which are interesting. We wrapped our patients in these electrodes to disrupt localization and orientation of polar molecules, which are microtubules, and combine this with weekly paclitaxel versus weekly paclitaxel alone. And this was ENGOT-ov50, or GOG-3029. This study completed accrual and is expected to readout in 2023. This would be the next big readout other than MIRASOL for hopefully another confirmed new technology for our patients and many other things to come.

A lot of activity in this space. A lot of trials ongoing. Some nearing results and presentations, which hopefully will change the standard of care for our patients, and lots of beautiful preclinical work ongoing to bring new drugs to trials for our patients.\

I think that's where I will stop. Thank you.

Source

Moore, K. Current and Emerging Therapies for Platinum-Resistant Ovarian Malignancies. Presented at: Great Debates & Updates in Women’s Oncology. Sep 21-23, 2022. Virtual.