Abstract CT109: Livmoniplimab and budigalimab combination therapy in treating patients with metastatic ovarian granulosa cell tumors: Results from dose escalation in a first-in-human study
Authors: Rivera Ildefonso Rodriguez , Sommerhalder David , Sahtout Mohammad , Ferlini Cristiano , Ngo Duyen , Jha Sujata , Engelhardt John , Tolcher Anthony 
Published: April 2024

Abstract
Background: Ovarian granulosa cell tumors (OGC) are rare, accounting for 5-7% of all ovarian cancers and fatal when metastatic. There are no approved targeted therapies for metastatic OGC. Several agents with different targets, such as pembrolizumab, nirogacestat, orteronel, and STM 434, are being evaluated but to date have not shown clinical benefit. Most OGC carry a C134W mutation in the FOXL2 gene, which manifests its protumor effects via the transforming growth factor (TGF)-β signaling pathway. Livmoniplimab (livmo) is a monoclonal antibody (mAb) that specifically binds to the TGF-β1-glycoprotein-A repetitions predominant protein complex, blocking the release of active TGF-β1. Livmo has been assessed with or without budigalimab (budi), an anti-PD-1 mAb, in the dose escalation (ESC) part of a first-in-human study in patients (pts) with advanced solid tumors, including OGC. Herein, we report results of 4 pts with OGC enrolled into the combination ESC part of this phase 1 study (NCT03821935).
Methods: Pts ≥18 years with ECOG PS 0-1 were enrolled in ESC, including pts with metastatic OGC refractory to/not eligible for standard therapies. The maximum tolerated dose was not reached, and pts received the maximum administered dose of 1500 mg livmo (Q2W IV) + 500 mg budi (Q4W IV). Safety and overall response rate (ORR) per RECIST v1.1 were assessed.
Results: As of 28 Sep 2023, 57 pts were enrolled in ESC, including 4 with metastatic OGC aged 50-63 years who received 3-7 prior lines of systemic therapy. In total, 98% (n=56) pts in ESC experienced TEAEs, most commonly fatigue (42%), nausea (37%), and anemia (37%). One pt with OGC was enrolled in the study with metastatic target lesions in the lung, liver, and peritoneum at screening. She had received 7 prior lines of therapy including doxorubicin, bevacizumab, anastrozole, tamoxifen, and carboplatin + paclitaxel. Upon treatment with livmo + budi, she had a deep partial response (-92% from baseline) and a complete response in the target liver lesion. The pt stayed in response for ~2.5 years before death due to an event unrelated to study drugs. Furthermore, 2 other pts with metastatic OGC had a partial response (ORR=75%) and none of the 4 pts with OGC experienced disease progression (disease control rate=100%).
Conclusions: Livmo + budi had promising antitumor efficacy and a tolerable safety profile in pts with metastatic OGC, a rare TGF-β signaling-dependent tumor. All enrolled pts with OGC showed tumor shrinkage and 1 pt had durable and near-complete response. Since single-agent pembrolizumab exhibited an ORR of 0% in pts with OGC (How et al. Invest New Drugs, 2021;39:829-835), we conclude that OGC is a proof-of-mechanism indication for livmo and that targeting TGF-β may represent an effective strategy for treating pts with OGC.
Citation Format: Ildefonso Rodriguez Rivera, David Sommerhalder, Mohammad Sahtout, Cristiano Ferlini, Duyen Ngo, Sujata Jha, John Engelhardt, Anthony Tolcher. Livmoniplimab and budigalimab combination therapy in treating patients with metastatic ovarian granulosa cell tumors: Results from dose escalation in a first-in-human study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT109.