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
NCT ID: NCT06253494
Last Updated: 2025-12-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1/PHASE2
60 participants
INTERVENTIONAL
2024-05-14
2028-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Mirvetuximab Soravtansine (IMGN853) and Bevacizumab in Patients With Endometrial Cancer
NCT03836157
A Study of Lifileucel (Tumor-infiltrating Lymphocytes) in Adults With Advanced Endometrial Cancer.
NCT06481592
A Study to Evaluate the Safety and Therapeutic Activity of GI-102 As a Single Agent and in Combination with Conventional Anti-cancer Drugs, Pembrolizumab or Trastuzumab Deruxtecan(T-DXd) in Patients with Advanced Solid Tumors (KEYNOTE-G08)
NCT05824975
Study of Immune Response Modifier in the Treatment of Breast, Ovarian, Endometrial and Cervical Cancers
NCT00319748
Autologous Tumor Infiltrating Lymphocytes MDA-TIL in Treating Patients With Recurrent or Refractory Ovarian Cancer, Colorectal Cancer, or Pancreatic Ductal Adenocarcinoma
NCT03610490
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
* Endometrial cancer (EC) is the most common gynecologic cancer in the US and the incidence peaks around 50-60 years of age. 5-year overall survival in patients with metastasis is around 20 percent and treatment after the second-line treatment has not been effective for long-term control.
* Pembrolizumab is approved for microsatellite instability (MSI)-high endometrial cancer which is rare.
* Pembrolizumab and lenvatinib combination therapy as second-line therapy in patients with advanced or metastatic EC showed promising antitumor activity. Recently, the Food and Drug Administration (FDA) approved pembrolizumab and lenvatinib in patients with advanced endometrial cancer who received prior chemotherapy after decades of lapse in adding new treatment options with an improved progression free survival (PFS) 6.6 months (vs 3.8 months in standard care chemotherapy), overall response rate 30 percent and median duration of response of 9.2 months.
* HER2 is positive in 30 percent of endometrial cancer and anti-HER2 therapy has shown clinical benefit in metastatic EC. Trastuzumab is used off-label with chemotherapy and as maintenance.
* An autologous dendritic cell vaccine that is transduced with an adenoviral vector expressing extracellular domain and transmembrane domain of HER2 (AdHER2DC vaccine) was well tolerated and showed a preliminary clinical benefit of 33.3 percent among 21 evaluable patients (NCT01730118, total enrolled n=33). No cardiotoxicity was noted. Immunogenicity analysis in a limited number of patients suggested induction of both humoral and cellular immune responses.
* The combination of pembrolizumab and lenvatinib in EC showed antitumor activity with manageable toxicity but still showed the responses in a limited group of patients. To overcome the resistance to immune checkpoint inhibitors, the combination regimen to induce the antitumor immune response by the AdHER2 vaccine, control the negative immune regulators and hostile tumor microenvironment by vascular endothelial growth factor (VEGF) inhibitor lenvatinib, and an immune stimulatory cytokine IL-15 superagonist N-803 has the potential to make the tumor more responsive to the immunotherapy creating mutual synergy.
OBJECTIVES:
* Phase I: To estimate recommended Phase II dose (RP2D) of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancer
* Phase II: To preliminarily assess the efficacy of a combination of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancer as determined by the proportion of participants without progression at 6 months
ELIGIBILITY CRITERIA:
* Age \>=18 years.
* Metastatic or locally advanced endometrial cancer with HER2 immunohistochemistry (IHC) 1+, 2+ or 3+.
* Progressed after at least 1 line of standard of care (SOC) systemic therapy Participants may have received any number of prior cytotoxic agents.
* ECOG performance status \<=2 and adequate organ function.
DESIGN:
* An open-label, two-arm, phase I/II study of pembrolizumab, lenvatinib, N-803, and AdHER2.
* During Phase I, we will estimate recommended Phase II dose (RP2D) of the lenvatinib in combination with AdHER2DC vaccine, pembrolizumab, and N-803.
* During Phase II we will continue to evaluate the safety and examine the efficacy of the study regimen at the RP2D of the lenvatinib in combination with AdHER2 DC vaccine, pembrolizumab, and N-803.
* Participants will undergo apheresis, and AdHER2DC vaccine will be generated by transducing the participants monocyte-derived dendritic cells with AdHER2 vector.
* Treatment will be delivered for up to 1 year or until progression or unacceptable toxicity.
* Up to 27 participants will be treated on this trial.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm 1
AdHER2DC vaccine + pembrolizumab + de-escalating doses of lenvatinib
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
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
Arm 2
AdHER2DC vaccine + N-803 + pembrolizumab + RP2D of lenvatinib
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
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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.
18 Years
120 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Hoyoung M Maeng, M.D.
Role: PRINCIPAL_INVESTIGATOR
National Cancer Institute (NCI)
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Konecny GE, Santos L, Winterhoff B, Hatmal M, Keeney GL, Mariani A, Jones M, Neuper C, Thomas B, Muderspach L, Riehle D, Wang HJ, Dowdy S, Podratz KC, Press MF. HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer. Br J Cancer. 2009 Jan 13;100(1):89-95. doi: 10.1038/sj.bjc.6604814. Epub 2008 Dec 16.
Makker V, Colombo N, Casado Herraez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309-KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. doi: 10.1056/NEJMoa2108330. Epub 2022 Jan 19.
Constantine GD, Kessler G, Graham S, Goldstein SR. Increased Incidence of Endometrial Cancer Following the Women's Health Initiative: An Assessment of Risk Factors. J Womens Health (Larchmt). 2019 Feb;28(2):237-243. doi: 10.1089/jwh.2018.6956. Epub 2018 Nov 28.
Related Links
Access external resources that provide additional context or updates about the study.
NIH Clinical Center Detailed Web Page
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
001557-C
Identifier Type: -
Identifier Source: secondary_id
10001557
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.