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OncoMatch/Clinical Trials/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

Is NCT06253494 recruiting? Yes, currently enrolling (Jun 2026). This Phase 1/2 trial studies multiple treatments for endometrial cancer.

Phase 1/2RecruitingNational Cancer Institute (NCI)NCT06253494Data as of Jun 2026

Treatment: AdHER2DC vaccine · Pembrolizumab · N-803 · Lenvatinib · PATHWAY HER2 (4B5) assayBackground: 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.

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Extracted eligibility criteria

Treatments studied

Immunotherapy

Pembrolizumab

Targeted therapy

Lenvatinib

Other

AdHER2DC vaccineN-803PATHWAY HER2 (4B5) assay

Cancer type

Endometrial Cancer

Biomarker criteria

Required: HER2 (ERBB2) IHC 1+, 2+ or 3+ overexpression (IHC 1+, 2+ or 3+)

HER2 IHC 1+, 2+ or 3+ tumor confirmed by PATHWAY HER2 (4B5) test

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Demographics

Ages ≤ 120

Prior therapy

Min 1 prior line

Must have received: systemic therapy — endometrial cancer

Participants must have received and progressed after at least one (1) line of systemic therapy for endometrial cancer.

Cannot have received: immune checkpoint inhibitor (anti-CTLA, anti-PD-1, anti-PD-L1, anti-TIGIT, anti-TIM3, anti-LAG3)

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.

Cannot have received: VEGFR inhibitor (lenvatinib)

History of Lenvatinib use

Lab requirements

Blood counts

ANC > 1,000/microliter; Platelets > 100,000/microliter; Hemoglobin > 9 g/dL (any number of transfusions within 60 days before apheresis is allowed)

Kidney function

Estimated creatinine clearance <=1.5 X ULN OR >30 mL/min/1.73 m2 for creatinine >1.5 X ULN

Liver function

Total bilirubin <=1.5 X ULN (<=3.0 X ULN with Gilbert's Syndrome or liver metastasis); AST/ALT <=3.0 X ULN (<=5.0 X ULN with liver metastasis)

Cardiac function

Fridericia's corrected QT interval (QTcF) < 480 msec; no evidence of third-degree AV block on ECG; ejection fraction by echocardiogram >= 50 percent; NYHA Functional Capacity III or IV or Objective Assessment C or D excluded

Participants must have adequate organ and marrow function as defined below: ... 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. Functional or objective cardiac dysfunction: New York Heart Association (NYHA) Functional Capacity III or IV or Objective Assessment C or D.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • National Institutes of Health Clinical Center · Bethesda, Maryland

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Frequently asked questions

Is NCT06253494 currently recruiting?

Yes, this trial is currently recruiting patients.

Are there prior therapy exclusions?

Yes. Prior immune checkpoint inhibitor, VEGFR inhibitor disqualifies patients from enrollment.

Does this trial require ERBB2?

Yes, ERBB2 IHC 1+, 2+ or 3+ overexpression is a required biomarker for enrollment.

Is there an age limit?

Yes. Patients must be 120 years or younger.

Could you qualify for this trial?

Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.

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