Pembrolizumab, Lenvatinib, N-803, and AdHER2DC Vaccine for HER2-Positive Endometrial Cancer
This study is testing a combination of treatments for advanced or metastatic endometrial cancer that has higher levels of a protein called HER2. Researchers are studying four treatments: AdHER2DC vaccine (which targets HER2), N-803 (which boosts immune cells), pembrolizumab (a checkpoint inhibitor), and lenvatinib. You may be able to join if you are an adult with HER2-positive endometrial cancer that has spread or returned after previous treatment. The study aims to find the best dose for these treatments and see how well they work together to shrink tumors. The current status of this study is unclear, and it plans to enroll 60 participants.
- Study design
- This interventional study plans to enroll 60 participants. It is testing a combination of four treatments, including a vaccine made from your own blood.
- What's involved
- You will receive the AdHER2DC vaccine through skin injections, pembrolizumab through IV infusions, N-803 through subcutaneous injections, and lenvatinib orally. The AdHER2DC vaccine involves apheresis, where blood is taken, processed, and returned to you.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will assess the best dose within the first 28 days of treatment and check for treatment effectiveness at 6 months.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
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
Recruiting
PHASE1Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~60 participants
Updated 2026-04-09 on ClinicalTrials.gov
What's tested:AdHER2DC vaccinePembrolizumabN-803LenvatinibPATHWAY HER2 (4B5) assay
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Phase I: Estimate recommended RP2D of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancer
Measured over Days 1-28 of Cycle 1
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesMaryland1
Study leadership
- Hoyoung M Maeng, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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.
Exclusion
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).
Surgery to abdomen/pelvis/chest within 3 months prior to apheresis.
Other malignancies diagnosed within 24 months prior to apheresis. NOTE: Participants who completed treatment for in-situ carcinomas (e.g., breast, cervix, bladder), or basal or squamous cell carcinoma of the skin are eligible if no ongoing treatment is needed per Standard of Care.
Arterial or venous thromboembolism within 6 months prior to apheresis.
History of cerebrovascular accident or stroke (transient ischemic attack, hemorrhagic or ischemic) within 6 months prior to apheresis.
Functional or objective cardiac dysfunction: New York Heart Association (NYHA) Functional Capacity III or IV or Objective Assessment C or D.
Fridericia's corrected QT interval (QTcF) \>= 480 msec or evidence of third-degree AV block on screening electrocardiogram (ECG).
Ejection fraction by screening echocardiogram \< 50 percent.
Participants requiring therapeutic anticoagulation regimen(s) (e.g., warfarin, rivaroxaban, apixaban, dabigatran, edoxaban, low molecular weight heparin \[e.g., enoxaparin, dalteparin, tinzaparin\], heparin, fondaparinux).
History of gastrointestinal or non-gastrointestinal fistula \>= Grade 3 (CTCAE v.5.0).
Radiographic evidence of major blood vessel invasion/infiltration.
History of hemoptysis or tumor bleeding within 1 month prior to apheresis.
Current gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
Any form of primary immunodeficiency.
Participants with active autoimmune disease or a history of autoimmune disease, which require immune suppressive treatment such as systemic corticosteroids or other systemic immune suppressants (e.g., methotrexate, cyclosporine, and biologics). NOTE: Participants with vitiligo, endocrine deficiencies on replacement dose are eligible.
Systemic corticosteroid therapy of higher than a physiologic dose (the equivalent of prednisone 10 mg/day) within 14 days prior to apheresis. NOTE: Any topical steroid medications (e.g., corticosteroid creams, ointments, and eye drops) are allowed.
Solid organ or allogeneic hematopoietic stem cell transplant recipients.
Human immunodeficiency virus (HIV)-positive participants.
Pregnancy (confirmed with beta-Human chorionic gonadotropin (HCG) serum or urine pregnancy test performed in IOCBP at screening).
Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.
What this trial measures
- Phase I: Estimate recommended RP2D of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancerDays 1-28 of Cycle 1
Number of Dose Limiting Toxicities (DLT).
- Phase II: Preliminarily assess the efficacy of a combination of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancer6 months
Defined as the time from the start of treatment to time of progression, death, or 6 months. The fraction who can be alive without progression at 6 months will be reported along with an 80% two-sided confidence interval (the lower bound is the one-sided 90% bound, which will be used to compare to an estimated 54-55% from the Makker 2022 result) and a 95% two-sided confidence interval.