Background:
Endometrial cancer (EC) of the uterus is becoming more common in the US. Sometimes EC often has increased levels of a protein called HER2. Cancers with HER2 tend to be more aggressive and have poorer outcomes.
Objective:
To test 2 study drugs-a vaccine that targets HER2 (AdHER2DC) plus a drug that supercharges immune cells that kill tumor cells (N-803)-combined with 2 FDA-approved cancer treatment drugs in people with EC.
Eligibility:
Adults aged 18 and older with HER2-positive EC that returned or got worse after treatment.
Design:
AdHER2DC vaccine is made from each participant s own blood. Participants will undergo apheresis: Blood is removed from the body through a tube attached to a needle. The blood passes through a machine that separates out the target cells. The remaining blood is returned to the body through a second needle. A special catheter may be needed.
The first treatment cycle is 28 days; each cycle after that will be 21 days.
All participants will get the 2 approved drugs and the vaccine. One drug is a tablet taken by mouth once a day, every day. The other drug is given through a tube attached to a needle inserted into a vein.
The vaccine is injected under the skin. Participants will receive the vaccine on day 1 of cycles 1, 2, and 3. Additional doses up to 3 doses will be give if possible.
Some participants will receive N-803. This drug is injected under the skin of the abdomen on day 1 of each cycle.
Treatment may last up to 1 year. Follow-up visits will continue up to 2 more years.
Histologically confirmed endometrial cancer.
Radiographically confirmed metastatic or locally advanced disease.
Evaluable (measurable or non-measurable) disease, per RECIST 1.1.
HER2 IHC 1+, 2+ or 3+ tumor confirmed by PATHWAY HER2 (4B5) test. NOTE: The HER2 status in participants who had prior anti-HER2 therapy should be confirmed in the tumor tissue obtained after completing the anti-HER2 therapy.
Administration of any standard of care or investigational checkpoint inhibitors (e.g., anti-CTLA, anti-PD-1, anti-PD-L1, anti-TIGIT, anti-TIM3, or anti-LAG3 antibodies or small molecules) within 6 months prior to apheresis.
History of grade 3 or 4 immune related adverse events from the use of immune checkpoint inhibitors.
History of Lenvatinib use
History of severe immediate hypersensitivity reaction to compounds similar to study drugs or their components (e.g., monoclonal antibody preparations).