Novel Antibody-Drug Conjugate to Be Tested in Lung, Gynecologic Cancers

In the second half of 2024, researchers will seek authorization to begin clinical trials with the novel antibody-drug conjugate.

The Food and Drug Administration (FDA) has cleared an investigational new drug application for ZW191 for patients with ovarian and other gynecologic cancers and patients with non-small cell lung cancer (NSCLC).

ZW191 is a novel drug called a folate receptor-alpha (FRα) targeted topoisomerase I inhibitor antibody-drug conjugate, according to a news release from Zymeworks, the drug’s manufacturer.

An antibody-drug conjugate (ADC) is a substance made from monoclonal antibodies that is chemically linked to a drug. It works by binding to receptors on cancer cells, according to the National Cancer Institute. The linked drug then enters and destroys the cancer cells without affecting the other cells.

According to a study published in the journal Nature, FRα is a type of glycoprotein that binds to folic acid that “mediates cellular processes, including cell division, proliferation and tissue growth.”

READ MORE: What Patients With Breast Cancer Need to Know About ADC-Related Fatigue

“Developed to target [folate receptor-alpha], which is expressed in several types of difficult-to-treat cancers, ZW191 incorporates a novel antibody and drug-linker that provide a unique combination of antibody-linker stability and payload potency, together with strong bystander activity, which could result in improved efficacy and enable targeting lower levels of [folate receptor-alpha] compared to previously developed drug candidates,” Paul Moore, chief scientific officer of Zymeworks, said in the release.

The manufacturing company designed ZW191 using its drug conjugate platforms, which also included a similar drug, ZD06519, targeting folate receptor-alpha-expressing tumors. These tumor types include ovarian cancer, other gynecological cancers and NSCLC, the news release stated.

Folate receptor-alpha expressions are clinically validated as treatment targets, the release noted. Interestingly, this type of expression is in approximately 75% of ovarian cancers and 70% of NSCLC, the release said.

READ MORE: FDA Fast Tracks Novel ADC for Ovarian Cancer Treatment

So far, the novel drug has shown beneficial anti-tumor activity and a good safety profile through preclinical models (meaning those that were not performed in humans), according to the news release.

Researchers developing ZW191 expect a balance between the tolerability and efficacy of the drug.

During the second half of 2024, Zymeworks aims to file applications to seek authorization to begin clinical trials for ZW191 in areas outside of the U.S.

Moore said in the news release. “We are pleased to reach this R&D milestone following on the heels of our recent FDA clearance for ZW171 in June and look forward to initiating clinical development of both ZW191 and ZW171 during 2024.”

Of note, Elahere (mirvetuximab soravtansine-gynx), another FRα drug, was FDA-approved in March this year for patients with epithelial ovarian, fallopian tube or primary peritoneal cancer who previously received treatment and are platinum-resistant. This approval was based on findings from the phase 3 MIRASOL trial, which included 453 patients and compared Elahere with standard-of-care chemotherapy, a study published in the Journal of Clinical Oncology showed.

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