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

Launched by NATIONAL CANCER INSTITUTE (NCI) · Feb 9, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for people with advanced or metastatic endometrial cancer, particularly those whose cancer shows higher levels of a protein called HER2. The treatment combines a vaccine made from the patient's own blood, which targets HER2, with two approved cancer drugs that help boost the immune system and fight cancer. This trial is looking for adults aged 18 and older who have previously received treatment for their cancer but have seen it return or worsen. To participate, patients must have confirmed HER2-positive endometrial cancer and be in good overall health.

Participants in this trial can expect to receive the new vaccine along with two standard cancer treatments over several treatment cycles lasting up to a year. The vaccine will be injected under the skin, while one of the drugs is taken as a daily pill, and the other is given through an IV. Follow-up visits will occur for up to two years after treatment to monitor progress. This trial is currently recruiting participants and aims to see if this combination can improve outcomes for patients with aggressive endometrial cancer.

Gender

ALL

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 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.