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
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.
• Participants must have received and progressed after at least one (1) line of systemic therapy for endometrial cancer.
• Age \>=18 years.
• ECOG performance status \<=2.
• Participants must have available tumor tissue or be willing to undergo a mandatory research biopsy. NOTE: Samples must be collected after HER2 directed therapy if the participant had anti-HER2 therapy.
• Participants must have adequate organ and marrow function as defined below:
‣ Absolute neutrophil count (ANC) \> 1,000/microliter
⁃ Platelets \> 100,000/microliter
⁃ Hemoglobin (Hgb) \> 9 g/dL (any number of transfusions within 60 days before apheresis is allowed)
⁃ Total bilirubin \<=1.5 X upper limit of normal (ULN). NOTE: In participants with Gilbert s Syndrome or known liver metastasis, total bilirubin \<=3.0 X ULN is allowed
⁃ Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) \<=3.0 X ULN. NOTE: AST/ALT \<=5.0 X ULN is allowed in participants with known liver metastasis
⁃ An estimated creatinine clearance (CrCl) \<=1.5 X ULN OR \>30 mL/min/1.73 m2 for participants with creatinine levels \>1.5 X ULN (calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl)
⁃ Dip stick urine protein \< 3 or urine protein \< 1 gram (g)/24 hour if dip stick urine is \>= 3+
• Hepatitis B virus (HBV)-infected participants can be enrolled if HBV DNA is undetectable. Hepatitis C virus (HCV)-infected participants can be enrolled if HCV RNA level is undetectable.
• Participants with previously treated non-active brain metastases or central nervous system metastases more than 28 days from definitive radiotherapy or surgery are eligible.
• Individuals of child-bearing potential (IOCBP) must agree to use highly effective contraception (hormonal, intrauterine device (IUD), tube ligation, a partner has had the previous vasectomy, abstinence) at the time of study entry, for the duration of study treatment, and up to 6 months after the last dose of the study drug(s).
• Nursing participants must be willing to discontinue nursing from study treatment initiation through 6 months after the last dose of the study drug(s).
• Participants must be able to understand and be willing to sign a written informed consent document.