Abstract CT046: A randomized, phase 2 study of pembrolizumab plus chemotherapy with or without anti—immunoglobulin-like transcript 4 monoclonal antibody MK-4830 as neoadjuvant treatment for high-grade serous ovarian cancer
Authors: Lee Jung-Yun , Bell Maria , Bidzinski Mariusz , Bodnar Lubomir , Chan Jack Junjie , Gill-Martin Marta , Ibanez Carolina , Lorusso Domenica , Lu Chien-Hsing , Rosengarten Ora , Townson Steven M. , Kobie Julie , Zhang Yiwei , Pruitt Scott , Shapira-Frommer Ronnie 
Published: April 2023

Abstract
Background: Combination therapy with the anti-PD-1 monoclonal antibody (mAb) pembrolizumab and chemotherapy in advanced solid tumors has shown efficacy in the (neo)adjuvant and first-line setting, including high-grade serous ovarian cancer (HGSOC). The immunoglobulin-like transcript 4 (ILT4) receptor expressed on myeloid cells is involved in immune tolerance and suppression within the tumor microenvironment, and its blockade may improve treatment outcomes with combination therapies. Pembrolizumab plus chemotherapy with or without MK-4830 (a novel humanized anti-ILT4 mAb) will be investigated as neoadjuvant therapy for HGSOC in a randomized, open-label, phase 2 study (NCT05446870). Specifically, this trial is designed to evaluate the utility of circulating tumor DNA (ctDNA) as a biomarker of response and minimal residual disease in patients with treatment-naive HGSOC.
Methods: Key eligibility criteria include adult patients with treatment-naive International Federation of Gynecology and Obstetrics Stage IIIA-C/IV HGSOC, primary peritoneal cancer, or fallopian tube cancer who are candidates for neoadjuvant and adjuvant chemotherapy and interval debulking surgery (IDS), and have an ECOG performance status of 0 or 1. Approximately 160 patients will be randomly assigned (1:1) to receive 3 cycles each of neoadjuvant and adjuvant therapy with patients in arm 1 receiving chemotherapy (carboplatin AUC 5 or 6 plus paclitaxel 175 mg/m2 or docetaxel 75 mg/m2) + pembrolizumab 200 mg and patients in arm 2 receiving chemotherapy + pembrolizumab + MK-4830 800 mg. Bevacizumab (or biosimilar) may be added to either arm in the adjuvant setting. All treatments will be given on day 1 of each 3-week cycle. For patients who undergo IDS, the last dose of neoadjuvant therapy will be administered 3-6 weeks before IDS, and adjuvant therapy will commence &lt;7 weeks after IDS. Adjuvant therapy will be administered for up to 3 cycles or until disease progression, unacceptable toxicity, or withdrawal. Upon completion of adjuvant therapy, patients may undertake maintenance therapy per investigator discretion and local guidelines. Tumor imaging will be performed at baseline, ≥21 days after neoadjuvant therapy or prior to IDS, after IDS or prior to the start of adjuvant therapy, and at the end of treatment. The primary objective is to evaluate the change from baseline in ctDNA, defined as the continuous mean mutant/tumor molecules/mL as measured in a blood sample, at cycle 3. Secondary objectives are to evaluate the association between change from baseline in ctDNA at cycle 3 and surgical outcomes (including pathologic complete response and chemotherapy response score), and safety and tolerability. Enrollment is ongoing.
Citation Format: Jung-Yun Lee, Maria Bell, Mariusz Bidzinski, Lubomir Bodnar, Jack Junjie Chan, Marta Gill-Martin, Carolina Ibanez, Domenica Lorusso, Chien-Hsing Lu, Ora Rosengarten, Steven M. Townson, Julie Kobie, Yiwei Zhang, Scott Pruitt, Ronnie Shapira-Frommer. A randomized, phase 2 study of pembrolizumab plus chemotherapy with or without anti—immunoglobulin-like transcript 4 monoclonal antibody MK-4830 as neoadjuvant treatment for high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT046.