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Novel Targeted Agents Emerging in Ovarian Cancer

Angelica Welch
Published: Thursday, Nov 15, 2018

Diana P. English, MD

Diana P. English, MD

Among the recent success in the ovarian cancer landscape with PARP inhibitors, many novel agents have also emerged and are paving paths in various settings of the disease.

Antibody-drug conjugates (ADCs) are being evaluated in ovarian cancer. Mirvetuximab soravtansine is currently being investigated in the phase III FORWARD I trial (NCT02631876). In this study, mirvetuximab soravtansine is being compared with investigator’s choice of chemotherapy in patient’s with platinum-resistant disease, explained Diana P. English, MD, a gynecologic oncologist at Stanford Hospital and Clinics.

English also noted that p53 mutation is a target of interest in ovarian cancer. Although drugs are still in trials for the treatment of patients with ovarian cancer who harbor p53 mutations, she emphasized the importance of tumor profiling in this disease. These panels give results that are now actionable, and may help patients who have specific alterations.

In an interview during the 2018 OncLive® State of the Science Summit™ on Ovarian Cancer, English discussed the promise for ADCs in the landscape of ovarian cancer treatment and targeting p53 mutations in patients with ovarian cancer.

OncLive: Could you please provide an overview of your presentation?

English: I spoke about novel treatment options in ovarian cancer, namely ADCs, and a bit about p53 reactivation drug therapy. The most promising thing would be the ADCs that are already in phase III trials. 

Namely the ADC, mirvetuximab soravtansine, which targets the folate receptor-alpha (FRα). This ADC has the antibody specific to the FRα. It is linked to a cytotoxic agent, which is the antimicrotubular agent DM4. The specificity of the antibody for the FRα, allows us to target tumor cells that tend to have a high expression of FRα.

About 80% of ovarian cancers overexpress FRα, and about 60% of ovarian cancers express it at high levels. [Overexpression is] anywhere from 50% to 75% of tumor cells with intense staining on immunohistochemistry. In the population of patients who are platinum resistant and not heavily pretreated—less than 3 prior lines—this drug has shown some very meaningful and promising results, with objective response rates around 39%.

It is now being looked at in a phase III clinical trial, called FORWARD I, and being compared with physician’s choice in platinum-resistant ovarian cancer. The physician’s choice options include the typical single agents that we use in platinum-resistant ovarian cancer such as doxorubicin, topotecan, and paclitaxel. The typical single agents used in this setting have response rates in the range of 10% to 20%. This ADC does seem to hold promise.

Are there any other ADCs in development?

There are other ADCs targeting other antigens or proteins that are overexpressed in ovarian cancer. One [target] is mesothelin, which is expressed on the majority of ovarian cancers. There is an ADC called anetumab ravtansine that is targeting the mesothelin protein. This ADC is conjugated to the antimicrotubular agent DM4. It did show some promise in ovarian cancer, but there were more meaningful results in mesothelioma. There is a phase II trial looking at this ADC in combination with bevacizumab (Avastin) versus bevacizumab plus paclitaxel in platinum-resistant disease.

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