Ongoing ADC Development Continues to Gain Traction in Ovarian Cancer

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Sarah Crafton, MD, discusses the ongoing development of agents targeting key biomarkers in ovarian cancer, such as FRα and HER2; expands on the integration of mirvetuximab soravtansine into clinical practice and its investigation in earlier lines; and emphasizes the importance of continued patient enrollment onto ongoing or planned ADC trials in ovarian cancer.

Sarah Crafton, MD

Sarah Crafton, MD

The approval of mirvetuximab soravtansine-gynx (Elahere) in ovarian cancer signals an increasing interest in the potential role for antibody-drug conjugates (ADC) in ovarian cancer, according to Sarah Crafton, MD, who added that the agent’s approval has bolstered ongoing and planned efforts to identify novel targets for ADC development.

On November 14, 2022, the FDA granted accelerated approval to mirvetuximab soravtansine for the treatment of adult patients with folate receptor α (Frα)–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received 1 to 3 prior systemic treatment regimens. The decision was based on findings from the phase 3 MIRASOL trial (NCT04209855), in which the ADC improved progression-free survival, objective response rate, and overall survival vs investigator’s choice of single-agent chemotherapy.

An application for conversion of this indication to full approval was granted priority review by the FDA in December 2023.

“ADCs are a unique new novel class of anti-cancer therapies that have certainly had some success in ovarian cancer,” said Crafton regarding her presentation at a recent OncLive® State of the Science Summit™ on gynecologic oncology. “Everyone was very excited for the FDA accelerated approval of mirvetuximab soravtansine in the fall of 2022. The information to date highlight that this is going to be a developing class of drugs in ovarian cancer.”

In an interview with OncLive, Crafton discussed the ongoing development of agents targeting key biomarkers in ovarian cancer, such as FRα and HER2; expanded on the integration of mirvetuximab soravtansine into clinical practice and its investigation in earlier lines; and emphasized the importance of continued patient enrollment onto ongoing or planned ADC trials in ovarian cancer.

Crafton is a gynecologic oncologist at Allegheny Health Network in Pittsburgh, Pennsylvania.

OncLive: What are some key biomarkers of interest for drug development in ovarian cancer?

Crafton: Based on the active trials that are recruiting, FRα is a very popular target and biomarker for ADCs in ovarian cancer. NaPi2b was the target of interest for the drug upifitamab rilsodotin (UpRi; XMT-1536), developed by Mersana. As of summer 2023, this drug is unfortunately no longer in development, and as of [my] last query on clinical trials.gov, it doesn’t look like there’s any ongoing development of that biomarker at this time.

In my presentation [I discussed] a trial of tisotumab vedotin-tftv [Tivdak], which has current FDA approval for cervical cancer. There was a trial in platinum-resistant ovarian cancer, which has been completed with some preliminary data. Final publication [of the data] is still pending, but that’s something to keep an eye out for.

[There is also research surrounding] HER2, which we know is an important prognostic biomarker for many cancers. Now that we have the technology of an ADC and not just monoclonal antibody therapy, such as trastuzumab [Herceptin], this is going to be an ongoing target for development, not just for ovarian cancer, but in many other cancers.

What emerging ADCs in ovarian cancer have the potential to change the current treatment paradigm?

Any of the HER2 ADCs have the potential [to change practice]. We still need independent data in ovarian cancer, but the [phase 2] DESTINY-PanTumor02 [NCT04482309] trial that was presented at the 2023 ASCO Annual Meeting has [generated] excitement across the board. Although there was a very small number of [patients with gynecologic malignancies in this trial], HER2 is a biomarker that’s worth further pursuit and investigation. FRα is, by and large, the most popular and common target for ADCs in ovarian cancer. There are also a few trials right now investigating TROP-2 as another potential target for ADCs. That seems to be very early in development but is something to watch.

In your personal experience, how have the recent approvals of ADCs such as tisotumab vedotin in cervical cancer and mirvetuximab soravtansine in ovarian cancer affected clinical practice?

We were fortunate to have several trials with mirvetuximab soravtansine open at our clinical location. That experience gave us the opportunity to become comfortable with the treatment before it became a standard of care. [Accordingly], the transition of mirvetuximab soravtansine into my practice has been relatively seamless. One of the other [topics] I [hear about] is about adverse effects and toxicity profiles. With this class of medication, we can’t ignore ocular toxicities. However, because we were familiar with it in clinical trials, we also had the infrastructure [to mitigate them through] close relationships with our ophthalmologists at our institution. This made the incorporation of mirvetuximab soravtansine into our standard practice very seamless.

What is your main message for colleagues based on your presentation?

Active screening and recruitment to clinical trials in ovarian cancer is going to be the most important thing as we further investigate these ADCs. ADCs as a class of medications have a lot of potential for all cancers, particularly ovarian cancer given the success of mirvetuximab soravtansine. We’re excited to continue to enroll [patients in these] trials and await results from the ongoing trials we’re recruiting for.

[Ultimately], it is important to understand, recognize, and appreciate that novel therapeutics, not just historic cytotoxic therapies in various combinations, seem to be the new wave of present and future [research]. Familiarizing ourselves early on with the mechanism and toxicity profiles [of these agents] is important as we [expand] the treatment approaches we’re using.

Is there any ongoing research in ovarian cancer that you’d like to highlight?

We know [about] the FDA approval for mirvetuximab soravtansine in the platinum-resistant setting, but there are two ongoing trials [aiming to] move this drug into earlier lines of treatment. One of them is [the phase 3] GLORIOSA trial [NCT05445778]. This study is [evaluating] mirvetuximab soravtansine with or without bevacizumab [Avastin] as maintenance therapy in the platinum-sensitive [setting]. That trial is ongoing and recruiting patients.

There is also a [phase 2] investigator-initiated trial at the University of Alabama Birmingham using mirvetuximab soravtansine with carboplatin in the neoadjuvant setting [NCT04606914]. We’re excited about the results and potential of both of those trials.

Reference

FDA grants priority review of ImmunoGen’s supplemental biologics license application for Elahere (mirvetuximab soravtansine-gynx) in platinum-resistant ovarian cancer. News release. ImmunoGen, Inc. December 5, 2023. Accessed January 18, 2024. https://investor.immunogen.com/news-releases/news-release-details/fda-grants-priority-review-immunogens-supplemental-biologics

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