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.
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.
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).
Sequential
AdHER2DC vaccine
Biological/VaccineAdHER2DC 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
Biological/VaccinePembrolizumab is given by IV infusion on Day 8 of cycle 1 and Day 1 of cycles 2-16
N-803
Biological/VaccineN-803 is given by subcutaneous injections on Day 1 of cycles 1-16
Lenvatinib
DrugLenvatinib is taken orally on Days 8-28 on cycle 1 and every day of cycles 2-16
PATHWAY HER2 (4B5) assay
DeviceUsed during screening to estimate eligibility
Phase I: Estimate recommended RP2D of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancer
Number of Dose Limiting Toxicities (DLT).
Phase II: Preliminarily assess the efficacy of a combination of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancer
Defined as the time from the start of treatment to time of progression, death, or 6 months. The fraction who can be alive without progression at 6 months will be reported along with an 80% two-sided confidence interval (the lower bound is the one-sided 90% bound, which will be used to compare to an estimated 54-55% from the Makker 2022 result) and a 95% two-sided confidence interval.
Determine the safety of the combination of pembrolizumab, lenvatinib, N-803, and AdHER2DC vaccine in participants with HER2 positive endometrial cancer
For participants receiving 4 agents, their safety will be evaluated with respect to the grades and types of toxicities obtained. The results will be presented descriptively and tabled if appropriate.
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