This study is currently recruiting participants.
Number
001557-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Children;Fetuses;Neonates;Pregnant Women
Keywords
Cancer Vaccine; Combination of anti-cancer drugs; Immunotherapy; HER2 Positive Cancer
Recruitment Keyword(s)
None
Condition(s)
Endometrial Cancer; Cancer of Endometrium; Carcinoma of Endometrium; Endometrial Carcinoma
Investigational Drug(s)
Ad5f35HER2ECTM transduced autologous dendritic cell vaccine N-803
Investigational Device(s)
Intervention(s)
Biological/Vaccine: AdHER2DC vaccine Biological/Vaccine: Pembrolizumab Biological/Vaccine: N-803 Drug: Lenvatinib Device: PATHWAY HER2 (4B5) assay
Supporting Site
National Cancer Institute
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.
--Back to Top--
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 - Syphilis-infected participants can be enrolled if no signs of active infection as determined by an infectious disease specialist - Participants with previously treated non-active brain metastases or central nervous system metastases more than 28 days from definitive radiotherapy or surgery are eligible - Women of child-bearing potential (WOCBP) 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) - Breastfeeding participants must be willing to discontinue breastfeeding 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 - Prior 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) - 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% - 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) - 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 WOCBP at screening) - Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.
- 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
- Syphilis-infected participants can be enrolled if no signs of active infection as determined by an infectious disease specialist
- Participants with previously treated non-active brain metastases or central nervous system metastases more than 28 days from definitive radiotherapy or surgery are eligible
- Women of child-bearing potential (WOCBP) 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)
- Breastfeeding participants must be willing to discontinue breastfeeding 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
- Prior 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)
- 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%
- 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)
- 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 WOCBP at screening)
- Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.
Principal Investigator
Referral Contact
For more information: