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

Plain English Summary

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 a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Endometrial Cancer, Cancer of Endometrium, Carcinoma of Endometrium, Endometrial Carcinoma. This trial tests a new combination of treatments including a HER2-targeting vaccine, an immune-boosting drug, and two approved cancer drugs. It is for adults with advanced or metastatic endometrial cancer that has returned or worsened after previous treatment and has high levels of the HER2 protein. Participation involves receiving the vaccine by injection, taking a tablet, and receiving infusions or injections of the other drugs over a period of up to one year, followed by two years of follow-up. Alternative treatments may include other chemotherapy, hormone therapy, or targeted therapies depending on the patient's specific situation and prior treatments. The trial aims to enroll 60 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with endometrial cancer that has spread or cannot be treated with surgery. Patients whose cancer has a specific marker called HER2 (tested by a PATHWAY HER2 assay). Individuals whose cancer has progressed after at least one prior treatment. Patients must have good organ function and be willing to undergo a research biopsy if needed. This trial is studying Endometrial Cancer, Cancer of Endometrium, Carcinoma of Endometrium, Endometrial Carcinoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures will assess how well the combination therapy works in shrinking tumors and how safe it is, aiming to provide a new treatment option for patients with this specific type of The specific primary outcome measures are: Phase I: Estimate recommended RP2D of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancer (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 (6 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a need for more effective treatments for HER2-positive endometrial cancer, which is often more aggressive and harder to treat. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Endometrial Cancer, Cancer of Endometrium, Carcinoma of Endometrium, Endometrial Carcinoma, where improved treatment options are needed.

Investor Insight

This Phase 2 trial explores a novel combination therapy for a subset of endometrial cancer patients, potentially expanding treatment options and indicating a move towards personalized medicine in this Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific drugs being tested, how they are given, and the potential side effects. Understand that participation involves regular clinic visits for treatments, monitoring, and potential biopsies. Be prepared for a treatment period of up to one year, followed by two years of follow-up appointments. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 60 participants

Interventions

• BIOLOGICAL: 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
• BIOLOGICAL: Pembrolizumab — Pembrolizumab is given by IV infusion on Day 8 of cycle 1 and Day 1 of cycles 2-16
• BIOLOGICAL: N-803 — N-803 is given by subcutaneous injections on Day 1 of cycles 1-16
• DRUG: Lenvatinib — Lenvatinib is taken orally on Days 8-28 on cycle 1 and every day of cycles 2-16
• DEVICE: PATHWAY HER2 (4B5) assay — Used during screening to estimate eligibility

Primary Outcomes

• Phase I: Estimate recommended RP2D of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancer (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 (6 months)

Secondary Outcomes

• Determine the safety of the combination of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancer (While on treatment (up to 1 year) and at the Safety Follow Up visit (30 days after treatment completion).)

Full Eligibility Criteria

* 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 biol

Trial Locations

• National Institutes of Health Clinical Center, Bethesda, Maryland, United States

Frequently Asked Questions

Related Conditions

• Endometrial Cancer
• Uterine Cancer
• Gynecologic Cancers
• HER2-Positive Cancers
• Metastatic Cancer
• Recurrent Cancer
• Advanced Cancer
• Immunotherapy
• Targeted Therapy
• Cancer Vaccines

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