Comparing an Investigational Targeted Drug AZD5335 to Standard Treatments in People With Platinum‑Resistant Ovarian Cancer (TREVI‑OC‑01)

About the Study

This study is testing whether a new targeted therapy called AZD5335 works better than currently used treatments for people with platinum‑resistant ovarian, fallopian tube, or primary peritoneal cancer. The study is looking at how long people live without their cancer getting worse while taking AZD5335 compared with standard treatments. 

AZD5335 is a type of targeted therapy known as an antibody-drug conjugate (ACD). ACDs are made up of an antibody attached to chemotherapy. The antibody binds to the cancer cell and delivers the chemotherapy directly into the cell. 

This study is open to people whose cancer returned or got worse after receiving a PARP inhibitor. 

What the Study Involves

Before joining, each participant’s tumor will be tested for biomarker known as folate receptor alpha (FRα). Based on the results, participants will be placed into one of two groups. 

FRα‑High Group

People whose tumor is FRα-high will be randomly assigned to one of two groups. One group will receive the investigational drug AZD5335 and the other group will receive an FDA-approved drug called Elahere (mirvetuximab soravtansine). Both drugs are a type of targeted therapy known as an antibody-drug conjugate (ACD). ACDs are made up of an antibody attached to chemotherapy. The antibody binds to the cancer cell and delivers the chemotherapy directly into the cell. 

• AZD5335 group: People in this group will receive the investigational drug AZD5335 by intravenous (IV) injection every three weeks. 
• Standard of care group: People in this group will receive the drug Elahere (mirvetuximab soravtansine) by intravenous (IV) injection every three weeks.

FRα‑Low Group

People whose tumor is FRα-high will be randomly assigned to one of two groups. One group will receive the investigational drug AZD5335 and the other group will receive standard chemotherapy. 

• AZD5335 group: People in this group will receive the investigational drug AZD5335 by intravenous (IV) injection every three weeks. 
• Standard chemotherapy group: People in this group will receive their doctor's choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The frequency of treatment will depend on which chemotherapy is selected. 

Treatment continues until one of the following happens:

• The cancer gets worse
• Side effects become unacceptable or unsafe
• The participant or doctor decides to stop treatment for another medical reason
• The participant chooses to stop the study treatment

All participants will be followed for several years, even after they stop the study treatment.

People may be eligible if they have all of the following: 

• Are 18 years or older.
• High‑grade ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
• Cancer that is platinum‑resistant (it came back within 6 months after platinum chemotherapy).
• Received 1 to 3 prior lines of treatment
• Are well enough to receive single‑agent treatment.

• People with a known BRCA mutation must have already received a PARP inhibitor, if appropriate, unless they could not tolerate it.

People cannot participate if they have any of the following: 

• The cancer is primary platinum refractory, which means it didn't respond or got worse on platinum chemotherapy. 
• Active or chronic corneal (eye surface) problems.
• Have a history of serious lung inflammation (ILD or pneumonitis) or significant lung disease.