We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A phase II study of induction PD-1 blockade (nivolumab) in patients with surgically completely resectable mismatch repair deficient endometrial cancer.
- Authors
Jung-yun Lee; Yong Jae Lee; Yoo-Young LEE; Jeong-Yeol PARK; Hyun-Woong CHO; Myong Cheol LIM; Mi Kyung KIM; Jong-Min LEE
- Abstract
Background: Mismatch repair deficiency (MMRd) tumors are known to be highly immunogenic and of great interest for immune checkpoint inhibitor. However, there is no data about the complete response rate of programmed cell death protein 1 (PD-1) blockade and surgery in subjects with mismatch repair deficient surgically resectable endometrial cancer. In this regard, we suggest a window of opportunity study of induction PD-1 blockade (nivolumab) in patients with surgically resectable MMRd endometrial cancer. Methods: We designed a single-arm phase 2 investigatorinitiated study utilizing the nivolumab, an anti PD-1 blockade, in patients with surgically completely resectable mismatch repair deficient endometrial cancer. Additional inclusion criteria include clinical stage I-IIIC2, tumor specimen that demonstrates MMRd by immunohistochemistry or microsatellite instability as demonstrated by next-generation sequencing or polymerase chain reaction. Exclusion criteria include multiple primary cancers, residual adverse effects of prior therapy or effects of surgery. Patients are treated with nivolumab IV 480 mg every 4 weeks up to 6 months followed by standard surgery and/or adjuvant treatment. The primary endpoint of the study is the complete response rate of PD-1 blockade and surgery. Secondary endpoints include objective response rate, progression-free survival, overall survival, and adverse events. Correlative studies include genomic characterization of tumors, assessment of immune infiltration of tumor microenvironment, and serial circulating cell-free DNA and immune biomarkers. Thirty patients will be enrolled at 4 South Korea sites. The Simon's 2-stage minimax design was used. Complete response rate from the unacceptable rate of 27.5% to an acceptable rate of 50% with type I error of 0.05 and 80% power. In the first stage, we would enroll 15 patients. If there are 4 or fewer responders, the study will stop for futility; if there are 13 or more complete responders the study will stop for efficacy. In the second stage, we will enroll an additional 15 patients for a total of 30 patients on study.
- Subjects
SOUTH Korea; IMMUNOTHERAPY; ENDOMETRIAL cancer; HEREDITARY nonpolyposis colorectal cancer; PROGRAMMED cell death 1 receptors; NIVOLUMAB; IMMUNE checkpoint inhibitors; FALSE positive error
- Publication
Journal of Gynecologic Oncology, 2024, Vol 35, p24
- ISSN
2005-0380
- Publication type
Article
- DOI
10.3802/jgo.2024.35.S2.P7