Abstract CT131: RVU120 SOL-021: An open-label, single agent, phase I/II trial of RVU120 (SEL120) in patients with relapsed/refractory metastatic or advanced solid tumors

Abstract Background: CDK8 and its paralog CDK19 have central roles in maintenance of cancer cell viability and undifferentiated state for a variety of tumor types. (Dannappel et al. 2019; Rzymski et al. 2015; Philip et al. 2018). CDK8 and CDK19 work by incorporating in a mutually exclusive manner, into a Mediator kinase module, that reversibly associates with a protein complex regulator of RNA Polymerase II, to mediate gene transcription. Targeting cancer-specific gene transcription via CDK8/19 inhibition has potential for treatment of solid tumors. RVU120 (SEL120) is a selective CDK8/19 inhibitor with preclinical efficacy in hematologic malignancies and a variety of solid tumor types (Rzymski et al. 2017). RVU120 showed strong anticancer activity in preclinical triple-negative breast cancer (TNBC) models, especially in the mesenchymal stem-like (MSL) molecular subtype (Rzymski et al SABCS 2021). Methods: SOL-021 is a Phase I/II clinical trial of RVU120 in Patients with metastatic or advanced solid tumors, who have exhausted available treatments, currently ongoing in Poland and Spain under NCT05052255 clinical trial register number. RVU120 is administered as single oral dose every other day (QOD) for a total of 7 doses on Days 1, 3, 5, 7, 9, 11 and 13, in a 3-week treatment cycle until progression or unacceptable toxicity. The study is designed in 2 parts: Part 1 follows a 3+3 dose escalation design and has primary objectives to characterize the safety and tolerability of RVU120 (SEL120) as single agent in patients with different tumors types and determination of the RP2D. Secondary objectives include objective response rate (ORR) according to RECIST criteria v1.1, duration of response (DoR), disease-control rate, progression-free survival (PFS), overall survival (OS) and pharmacokinetic profile of RVU120.Part 2 will primarily explore the anti-tumor activity of RVU120 as single agent in different patient populations. Based on strong preclinical evidence of anticancer activity of RVU120 on TNBC cells (Tomasz Rzymski SABCS #1766), patients with relapsed/refractory TNBC will be enrolled. Additionally, relapsed/refractory patients agnostic of their solid tumor type and selected based on their biomarker profile will be enrolled. The total duration of the study is approximately 27 months (12 and 15 for part 1 and 2, respectively). Results: At 11 Feb 2022 data cut off, 5 patients have been enrolled in part 1 of the study and no SAE have been observed: First cohort, 75 mg, was closed on 24 Nov 2021 with no DLT observed; current ongoing cohort, 100 mg dose level, is expected to be closed in the upcoming week, and subsequent cohort, 125 mg, to be opened mid-March. Conclusion: The trial is continuing as planned; the next data analysis will occur first week of March 2022. Citation Format: Rafal Dziadziuszko, Elena Garralda, Noemi Angelosanto, Tomasz Rzymski, Renata Dudziak, Krzysztof Brzózka, Peter Littlewood, Hendrik Nogai, Axel Glasmacher, Iwona Lugowska. RVU120 SOL-021: An open-label, single agent, phase I/II trial of RVU120 (SEL120) in patients with relapsed/refractory metastatic or advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT131.