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Investigators will examine the combination with pembrolizumab and lenvatinib in patients with HER2-expressing endometrial cancer.
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Trial Name: 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
ClinicalTrials.gov ID: NCT06253494
Sponsor: National Cancer Institute (NCI)
Completion Date (Estimated): December 31, 2028
A phase 1/2 clinical trial, QUILT 502 (NCT06253494), evaluating nogapendekin alfa inbakicept-pmln (N-803, Anktiva; ImmunityBio Inc) in combination with the investigational autologous dendritic cells transduced with HER2-expressing adenovirus vaccine (AdHER2DC; ImmunityBio Inc) in patients with HER2-expressing endometrial cancer was announced. The trial will evaluate N-803 as an agent to replace the short-term activity of checkpoint inhibitor immunotherapies with long-term effectiveness.1
In April 2024, N-803 in addition with Bacillus Calmette-Guérin (BCG) was approved by the FDA for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ, with or without papillary tumors. The agent is a first-in-class interleukin-15 agonist immunotherapy for NMIBC and initially received a breakthrough therapy designation and approval following the safety and efficacy outcome of complete response and duration of compete response in a clinical trial.2
In addition, the AdHER2DC vaccine targets the HER2 protein, which is elevated by approximately 30% in patients who have endometrial cancer and is present in more that 50% of high-risk subtypes. AdHER2DCs are autologous and use the patient’s own blood cells obtained through apheresis, passed through a machine to filter out target cells, and then returned to the patient in a different vein.1
QUILT 502 will consist of a phase 1 segment and phase 2 segment, and the trial will assess whether the AdHER2DC vaccine in combination with N-803, the checkpoint inhibitor, pembrolizumab, and the kinase inhibitor, lenvatinib, can be safely administered in combination while providing preliminary clinical efficacy. The study authors are anticipating enrolling 60 patients and expect completion in 2026.1,3
The open-label, 2-arm phase 1 portion of the trial will determine the recommended dose of pembrolizumab, lenvatinib, N-803, and AdHER2DC in participants with HER2+ endometrial cancer. Pembrolizumab and lenvatinib have been both been approved by the FDA for indications in endometrial cancer. The phase 2 portion will assess the combination regimen’s efficacy, which will be determined by the proportion of participants without disease progression after a 6-month duration. The primary end points of phase 1 (number of dose limiting toxicities) and phase 2 (the efficacy of the treatment regimen) will be assessed on days 1 through 28 of cycle 1 and at 6 months, respectively.1,3
The AdHER2DC vaccine will be administered via intradermal injections on day 1 of cycles 1 through 3, followed by up to 3 optional boost doses on day 1 of cycles 6, 9, and 12. Pembrolizumab will be administered via intravenous infusion on day 8 of cycle 1 and day 1 of cycles 2 through 16. Additionally, lenvatinib will be given orally on days 8 through 28 on cycle 1, then every day of cycles 2 through 16. N-803 will be administered subcutaneously on day 1 of cycles 1 through 16.1,3
“We are pleased to partner with the NCI on this important cancer control study involving [N-803], which has demonstrated in clinical trials that activation of memory T cells may help deliver long-duration response well beyond that of checkpoint inhibitors alone,” said Patrick Soon-Shiong, MD, executive chairman and global chief scientific and medical officer at ImmunityBio, in a news release. “We are hopeful that the AdHER2DC investigational vaccine plus [N-803] will ‘rescue’ the checkpoint inhibitor pembrolizumab and kinase inhibitor lenvatinib and lead to an improved response compared with the current standard of care in this high-risk population.”1
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