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A Randomized Phase II Study of AGS-16C3F Versus Axitinib in Previously Treated Patients with Metastatic Renal Cell
Christian Kollmannsberger1, Toni K Choueiri2, Daniel Y C Heng3
1University of British Columbia, BC Cancer-Vancouver Cancer Centre, Vancouver, British Columbia, Canada.
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.
Insights
The investigational antibody-drug conjugate AGS-16C3F did not meet its primary endpoint in a phase II trial for metastatic renal cell carcinoma (mRCC). Axitinib demonstrated superior progression-free survival compared to AGS-16C3F in previously treated mRCC patients.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- AGS-16C3F is a novel antibody-drug conjugate targeting ENPP3, conjugated to a microtubule disruptive agent.
- This phase II study evaluated AGS-16C3F against axitinib in metastatic renal cell carcinoma (mRCC).
Purpose of the Study:
- To evaluate the efficacy and safety of AGS-16C3F compared to axitinib in previously treated mRCC patients.
- The primary objective was to assess progression-free survival (PFS).
Main Methods:
- Patients with mRCC and disease progression were randomized 1:1 to intravenous AGS-16C3F or oral axitinib.
- The primary endpoint was investigator-assessed PFS using RECIST version 1.1.
Main Results:
- Median PFS was 2.9 months for AGS-16C3F versus 5.7 months for axitinib (HR, 1.676; p = .015).
- No significant differences were observed in secondary endpoints like overall survival.
- Common adverse events included fatigue and nausea (AGS-16C3F) or fatigue and diarrhea (axitinib).
Conclusions:
- AGS-16C3F did not meet the primary endpoint in this phase II trial.
- The study provides a benchmark for axitinib use in heavily pretreated mRCC patients.
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