A Randomized Phase II Study of AGS‐16C3F Versus Axitinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma. (19th January 2021)

• Record Type: Journal Article
• Authors: Kollmannsberger, Christian; Choueiri, Toni K.; Heng, Daniel Y.C.; George, Saby; Jie, Fei; Croitoru, Ruslan; Poondru, Srinivasu; Thompson, John A.
• Is Part Of: Oncologist. Volume 26:Number 3(2021)
• Page Start: 182
• Page End: e361
• Publication Date: 2021-01-19
• Subjects: Randomized controlled trial -- AGS‐16C3F -- Axitinib -- Renal cell carcinoma; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1002/onco.13628
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: Trial Information : ClinicalTrials.gov Identifier: NCT02639182 Sponsor: Astellas Pharma, Inc. Principal Investigator: Christian Kollmannsberger IRB Approved: Yes Lessons Learned : The primary endpoint of this phase II study that evaluated the efficacy and safety of the investigational compound, AGS‐16C3F, versus axitinib in previously treated patients with metastatic renal cell carcinoma (mRCC) was not met. Median progression‐free survival, the primary endpoint, was 2.9 months with AGS‐16C3F and 5.7 months with axitinib (HR, 1.676; 95% CI, 1.107–2.537; p = .015), per investigator assessment The safety profile for each study drug was as expected, with the most commonly reported adverse events being fatigue (53%) and nausea (47%) in the AGS‐16C3F arm and fatigue (57%) and diarrhea (48%) in the axitinib arm. These results provide a benchmark for axitinib use in heavily pretreated patients with mRCC. Background: AGS‐16C3F is a novel antibody‐drug conjugate that targets cell‐surface ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) and is conjugated to a microtubule disruptive agent. Here we present findings from a phase II study of AGS‐16C3F versus axitinib in metastatic renal cell carcinoma (mRCC). Methods: Patients with mRCC of any histology and disease progression during or after their last treatment regimen were randomized 1:1 to intravenous AGS‐16C3F 1.8 mg/kg every 3 weeks or oral axitinib 5 mg twice daily (starting dose). The primary objective was investigator‐assessed progression‐free survival (PFS) of AGS‐16C3F versus axitinib (RECIST version 1.1). Results: In the total population ( N = 133), 63% ( n = 84) of patients had completed the study at data cutoff (August 21, 2019). Median PFS was 2.9 months with AGS‐16C3F and 5.7 months with axitinib (hazard ratio [HR], 1.676; 95% confidence interval [CI], 1.107–2.537; p = .015). There were no significant differences between arms in secondary efficacy endpoints, including overall survival (13.1 months, AGS‐16C3F and 15.4 months, axitinib; HR, 1.079; 95% CI, 0.681–1.707; p = .747). In the safety population ( n = 131), the most commonly reported adverse events were fatigue (53%) and nausea (47%) in the AGS‐16C3F arm and fatigue (57%) and diarrhea (48%) in the axitinib arm. The incidence of diarrhea was lower in the AGS‐16C3F arm than in the axitinib arm (17% vs. 48%), and ocular toxicities were more frequent in the AGS‐16C3F arm than in the axitinib arm (44% vs. 26%). Conclusion: The investigational compound, AGS‐16C3F, did not meet the primary endpoint of this trial. These study results provide a benchmark for axitinib use in heavily pretreated patients with mRCC.