Comparing an Experimental Drug Puxi-Sam to Standard Chemotherapy for Metastatic Endometrial Cancer (Bluestar‑Endometrial01)

About the Study

This is a phase 3 study testing whether a new targeted drug called puxitatug samrotecan (Puxi-Sam) works better than standard chemotherapy for treating advanced or metastatic endometrial cancer which has grown or returned after prior treatment with platinum chemotherapy and an immunotherapy. Puxi-Sam 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. 

What the Study Involves

Participants will be randomly assigned to one of two groups:

• Group 1 participants will receive Puxi-Sam every 3 weeks by intravenous (IV) injection.
• Group 2 participants will receive their doctor's choice of chemotherapy given by intravenous (IV) injection. Chemotherapy may be  which may be:
  • Doxorubicin (IV once every 3 weeks), or
  • Paclitaxel (IV weekly for 3 weeks, then 1 week off)

All participants will be followed closely while they are receiving study treatment, with regular visits, scans, and safety checks.

After treatment stops, participants will continue to be followed to track:

• Whether the cancer worsens (progression)
• Overall survival
• Long‑term side effects
• Quality of life

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

• Are 18 years or older
• Have endometrial carcinoma or carcinosarcoma
• Have a biomarker called B7-H4
• Have recurrent or metastatic disease seen on scans
• Have already received:
  • Platinum‑based chemotherapy, and
  • A type of immunotherapy know as PD-1 or PD-L1
• Have had no more than 2 prior treatment lines for advanced/metastatic disease
• Have a good performance status (able to carry out daily activities)
• Have measurable disease on imaging scans

People cannot participate if they have any of the following: 

• Have a type of uterine cancer called uterine sarcoma or uterine neuroendocrine cancer
• Had a late recurrence (more than 12 months) after curative platinum therapy and did not receive platinum again
• Have previously been treated with:
  • Puxitatug samrotecan, or
  • Any other targeted therapy that targets B7-H4 cancers 
• Have received a type of treatment called a TOP1 inhibitor
• Have a history of serious lung inflammation (ILD or pneumonitis) or significant lung disease