Actively Recruiting

Phase 1
Phase 2
Age: 18Years - 120Years
All Genders
NCT06253494

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

Led by National Cancer Institute (NCI) · Updated on 2026-04-09

60

Participants Needed

1

Research Sites

241 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years - 120Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Histologically confirmed endometrial cancer
  • Radiographically confirmed metastatic or locally advanced disease
  • Evaluable disease according to RECIST 1.1 criteria
  • HER2 IHC 1+, 2+, or 3+ tumor confirmed by PATHWAY HER2 (4B5) test
  • Progressed after at least one line of systemic therapy for endometrial cancer
  • Age 18 years or older
  • ECOG performance status of 2 or less
  • Available tumor tissue or willingness to undergo mandatory research biopsy
  • Adequate organ and marrow function, including ANC > 1000/microliter, platelets > 100,000/microliter, hemoglobin > 9 g/dL, total bilirubin ≤ 1.5 times upper limit of normal (ULN) or ≤ 3.0 times ULN in specific cases
  • AST/ALT ≤ 3.0 times ULN or ≤ 5.0 times ULN in cases with liver metastasis
  • Estimated creatinine clearance > 30 mL/min/1.73 m2 or ≤ 1.5 times ULN
  • Dip stick urine protein < 3 or urine protein < 1 gram/24 hour if dip stick urine ≥ 3+
  • Hepatitis B virus (HBV) with undetectable DNA or Hepatitis C virus (HCV) with undetectable RNA
  • Previously treated non-active brain or central nervous system metastases more than 28 days after radiotherapy or surgery
  • Agreement to use highly effective contraception if of child-bearing potential
  • Willingness to discontinue nursing during treatment and for 6 months after last dose
  • Ability to understand and sign informed consent
Not Eligible

You will not qualify if you...

  • Use of checkpoint inhibitors within 6 months before apheresis
  • History of grade 3 or 4 immune-related adverse events from checkpoint inhibitors
  • Previous use of lenvatinib
  • Severe immediate hypersensitivity to study drugs or components
  • Surgery to abdomen, pelvis, or chest within 3 months before apheresis
  • Other malignancies diagnosed within 24 months before apheresis except treated in-situ carcinomas or certain skin cancers
  • Arterial or venous thromboembolism within 6 months before apheresis
  • Stroke or cerebrovascular accident within 6 months before apheresis
  • Severe cardiac dysfunction (NYHA III or IV) or low ejection fraction (<50%)
  • Corrected QT interval ≥ 480 msec or third-degree AV block on ECG
  • Requirement for therapeutic anticoagulation
  • History of grade 3 or higher gastrointestinal or non-gastrointestinal fistula
  • Major blood vessel invasion or infiltration
  • Recent hemoptysis or tumor bleeding within 1 month before apheresis
  • Conditions affecting absorption of lenvatinib
  • Primary immunodeficiency
  • Active or history of autoimmune disease requiring systemic immunosuppression
  • Systemic corticosteroid therapy above physiologic dose within 14 days before apheresis
  • Solid organ or allogeneic hematopoietic stem cell transplant recipients
  • HIV positive status
  • Pregnancy
  • Uncontrolled illness or conditions limiting study compliance

AI-Screening

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Trial Site Locations

Total: 1 location

1

National Institutes of Health Clinical Center

Bethesda, Maryland, United States, 20892

Actively Recruiting

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Research Team

M

Megan P Hausler, R.N.

CONTACT

H

Hoyoung M Maeng, M.D.

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

2

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