Recruiting

Phase 1

Phase 2

Pembrolizumab, Lenvatinib, N-803Pembrolizumab, 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

Sponsor:

National Cancer Institute (NCI)

Code:

NCT06253494

Conditions

Endometrial Cancer

Cancer of Endometrium

Carcinoma of Endometrium

Endometrial Carcinoma

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

AdHER2DC vaccine

Pembrolizumab

N-803

Lenvatinib

PATHWAY HER2 (4B5) assay

Study Details

Brief 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.

Conditions

Endometrial Cancer

Cancer of Endometrium

Carcinoma of Endometrium

Endometrial Carcinoma

Study ID

NCT06253494

Start date

May 14, 2024

Status verified date

Apr 7, 2026

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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 <=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 CRITERIA

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.

Study Design

Enrollment

60 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1

AdHER2DC vaccine + pembrolizumab + de-escalating doses of lenvatinib

experimental: Arm 2

AdHER2DC vaccine + N-803 + pembrolizumab + RP2D of lenvatinib

Interventions

AdHER2DC 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

Pembrolizumab

Pembrolizumab is given by IV infusion on Day 8 of cycle 1 and Day 1 of cycles 2-16

N-803

N-803 is given by subcutaneous injections on Day 1 of cycles 1-16

Lenvatinib

Lenvatinib is taken orally on Days 8-28 on cycle 1 and every day of cycles 2-16

PATHWAY HER2 (4B5) assay

Used during screening to estimate eligibility

Primary outcome measure

Phase I: Estimate recommended RP2D of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancer [ Time Frame: Days 1-28 of Cycle 1 ]
Phase II: Preliminarily assess the efficacy of a combination of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancer [ Time Frame: 6 months ]

Central Contacts and Locations

Central contacts

Megan P Hausler, R.N.

(240) 858-3544 megan.hausler@nih.gov

Hoyoung M Maeng, M.D.

(240) 781-3253 hoyoung.maeng@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

National Cancer Institute Referral Office

888-624-1937 NCIMO_Referrals@mail.nih.gov

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Apr 9, 2026

Last verified

Apr 7, 2026

Keywords

Cancer Vaccine
Combination of anti-cancer drugs
Immunotherapy
HER2 Positive Cancer

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-04-09.