Abstract CT049: VELOCITY-Lung: A phase 2 study evaluating safety and efficacy of sacituzumab govitecan (SG) + zimberelimab (zim) + etrumadenant (etruma) in patients (pts) with advanced or metastatic non-small cell lung cancer (mNSCLC) progressing on or after platinum (PT)-based chemotherapy and checkpoint inhibitors (CPI)
Authors: Rohatgi Anjali , Yang James Chih-Hsin , Kim Dong-Wan , Li Molly , Park Joseph , Seto Anna , Zhang Jie , Peled Nir 
Published: April 2023

Abstract
Background: Single-agent chemotherapy is the standard of care (SOC) in pts with mNSCLC progressing on or after PT-based chemotherapy and CPI but is associated with poor outcomes. SG is a Trop-2-directed antibody-drug conjugate. SG monotherapy demonstrated an objective response rate (ORR) of 17%, with a manageable safety profile in 54 pts with mNSCLC who had multiple prior therapies (Heist RS, et al. J Clin Oncol. 2017), and a phase 3 study is currently ongoing in this population (NCT05089734). Zim (anti-PD-1) and etruma (dual adenosine receptor antagonist) are under clinical investigation for anti-tumor activity. Zim+etruma and SG+CPI have been previously studied, with overall manageable safety profiles. Here we describe the design of substudy-02 of the VELOCITY-Lung phase 2 platform study, which will evaluate novel treatment combinations, including SG+zim+etruma, in pts with advanced or mNSCLC progressing on or after PT-based chemotherapy and CPI.
Methods: VELOCITY-Lung (NCT05633667) is an open-label, multicenter, randomized, phase 2 platform study, interrogating multiple diverse mechanisms of targeting tumor cells. Eligibility criteria include pathologically documented stage IV NSCLC, and progression after PT-based chemotherapy and CPI given either in combination or sequentially, including pts who received maintenance CPI for stage III disease. Pts with actionable genomic alterations must have received ≥1 previous targeted treatment. Pts will be enrolled into the preliminary stage treatment arm, SG+zim+etruma. After new treatment arms are added to this stage, or when the study proceeds to the expansion stage, patients will be randomized. The randomization ratio will be determined by the sponsor depending on the number of experimental arms initiated in the expansion stage, the comparator arm, and any newly added preliminary stage treatment arms. Randomization will be stratified by histology and prior therapy for actionable genomic alterations. Dosing is per recommended phase 2 dose or maximum tolerated dose for study agents and pts will continue to receive treatment until progressive disease, death, unacceptable toxicity, or initiation of a subsequent anticancer therapy. The primary endpoint is ORR assessed by investigator per RECIST v1.1. Secondary endpoints include progression-free survival, duration of response, OS, and safety. During the preliminary stage, efficacy will be compared against historical SOC; during the expansion stage, efficacy will be compared with an active comparator arm within the study. Depending on the number of treatment arms being tested in the expansion stage, this study plans to enroll ~23 to 133 patients globally and is open for recruitment.
Citation Format: Anjali Rohatgi, James Chih-Hsin Yang, Dong-Wan Kim, Molly Li, Joseph Park, Anna Seto, Jie Zhang, Nir Peled. VELOCITY-Lung: A phase 2 study evaluating safety and efficacy of sacituzumab govitecan (SG) + zimberelimab (zim) + etrumadenant (etruma) in patients (pts) with advanced or metastatic non-small cell lung cancer (mNSCLC) progressing on or after platinum (PT)-based chemotherapy and checkpoint inhibitors (CPI) [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 CT049.