Pembrolizumab, Lenvatinib and IL-15 Superagonist N-803 in Combination With HER2 Targeting Autologous Dendritic Cell (AdHER2DC) Vaccine in Participants With Advanced or Metastatic Endometrial Cancer
National Cancer Institute (NCI)
Summary
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.
Description
BACKGROUND: * Endometrial cancer (EC) is the most common gynecologic cancer in the US and the incidence peaks around 50-60 years of age. 5-year overall survival in patients with metastasis is around 20 percent and treatment after the second-line treatment has not been effective for long-term control. * Pembrolizumab is approved for microsatellite instability (MSI)-high endometrial cancer which is rare. * Pembrolizumab and lenvatinib combination therapy as second-line therapy in patients with advanced or metastatic EC showed promising antitumor activity. Recently, the Food and Drug Administrat…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * 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. * Participants must have received and progressed after at least one (1) line of systemic therapy for endometrial cancer. * Age \>=18 years. * ECOG performance status \…
Interventions
- BiologicalAdHER2DC vaccine
AdHER2DC vaccine is given by intradermal injections on Day 1 of cycles 1-3 (priming) followed by optional boost doses (up to 3), on Day 1 of cycles 6, 9, 12
- BiologicalPembrolizumab
Pembrolizumab is given by IV infusion on Day 8 of cycle 1 and Day 1 of cycles 2-16
- BiologicalN-803
N-803 is given by subcutaneous injections on Day 1 of cycles 1-16
- DrugLenvatinib
Lenvatinib is taken orally on Days 8-28 on cycle 1 and every day of cycles 2-16
- DevicePATHWAY HER2 (4B5) assay
Used during screening to estimate eligibility
Location
- National Institutes of Health Clinical CenterBethesda, Maryland