Joshua J McFarlane1, Mark D Kochenderfer2, Mark R Olsen3, Todd M Bauer4, Ana Molina5, Ralph J Hauke6, James A Reeves7, Sunil Babu8, Peter Van Veldhuizen9, Bradley Somer10, Vijay Gunuganti11, Ian Schnadig12, Saby George13, Ray D Page14, Edward Arrowsmith15, Rohit K Jain16, Joshua Zhang17, M Brent McHenry17, Jennifer L Johansen17, Nicholas J Vogelzang18. 1. Hematology/Oncology, Virginia Cancer Institute, Richmond, VA. Electronic address: jmcfarlane@vacancer.com. 2. Hematology and Medical Oncology, Blue Ridge Cancer Care, Roanoke, VA. 3. Medical Oncology, Oklahoma Cancer Specialists, Tulsa, OK. 4. Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, TN. 5. Department of Medicine, Weill Cornell Medicine, New York, NY. 6. Nebraska Cancer Specialists, Omaha, NE. 7. Florida Cancer Specialists/Sarah Cannon Research Institute, Fort Myers, FL. 8. Fort Wayne Medical Oncology and Hematology, Fort Wayne, IN. 9. Department of Medical Oncology, Research Medical Center, Kansas City, MO. 10. Medical Oncology, The West Clinic, Memphis, TN. 11. Department of Oncology, Cancer Care Centers of South Texas, San Antonio, TX. 12. Compass Oncology, Tigard, OR. 13. Roswell Park Cancer Institute, Buffalo, NY. 14. The Center for Cancer and Blood Disorders, Fort Worth, TX. 15. Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Chattanooga, TN. 16. Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL. 17. Bristol Myers Squibb, Princeton, NJ. 18. US Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV.
Abstract
BACKGROUND: The open-label, phase IIIb/IV CheckMate 374 study (NCT02596035) was conducted to validate the safety and efficacy of flat-dose nivolumab monotherapy 240 mg every 2 weeks (Q2W) in previously treated advanced/metastatic renal cell carcinoma (RCC). Three cohorts included patients with predominantly clear cell histology, non-clear cell histologies, or brain metastases. We report safety and efficacy from the CheckMate 374 advanced clear cell RCC (ccRCC) cohort. PATIENTS AND METHODS: Eligible patients received prior treatment regimens (1-2 antiangiogenic; 0-3 systemic) with progression on/after last treatment and ≤ 6 months of enrollment. Patients received nivolumab 240 mg Q2W for ≤ 24 months or until confirmed progression/unacceptable toxicity. The primary endpoint was incidence of high-grade (grade 3-5) immune-mediated adverse events (IMAEs). Exploratory endpoints included objective response rate, progression-free survival, and overall survival. RESULTS: Ninety-seven patients had advanced predominantly ccRCC; 75.3% received only 1 prior systemic regimen in the advanced/metastatic setting. After a median follow-up of 17 months (range, 0.4-26.9 months), no grade 5 IMAEs occurred, and 9.3% of patients reported grade 3/4 IMAEs (hepatitis, 4.1%; diabetes mellitus, 2.1%; nephritis and renal dysfunction, 1.0%; rash, 1.0%; adrenal insufficiency, 1.0%). The objective response rate was 22.7% (95% confidence interval [CI], 14.8%-32.3%). Three patients had a complete response; 19 had partial responses. The median progression-free survival was 3.6 months (95% CI, 2.0-5.5 months). The median overall survival was 21.8 months (95% CI, 17.4 months to not estimable). CONCLUSIONS: This study validates the safety and efficacy of nivolumab 240 mg Q2W flat-dose monotherapy for previously treated advanced ccRCC and adds to previous safety and efficacy data using the 3 mg/kg Q2W dose.
BACKGROUND: The open-label, phase IIIb/IV CheckMate 374 study (NCT02596035) was conducted to validate the safety and efficacy of flat-dose nivolumab monotherapy 240 mg every 2 weeks (Q2W) in previously treated advanced/metastatic renal cell carcinoma (RCC). Three cohorts included patients with predominantly clear cell histology, non-clear cell histologies, or brain metastases. We report safety and efficacy from the CheckMate 374 advanced clear cell RCC (ccRCC) cohort. PATIENTS AND METHODS: Eligible patients received prior treatment regimens (1-2 antiangiogenic; 0-3 systemic) with progression on/after last treatment and ≤ 6 months of enrollment. Patients received nivolumab 240 mg Q2W for ≤ 24 months or until confirmed progression/unacceptable toxicity. The primary endpoint was incidence of high-grade (grade 3-5) immune-mediated adverse events (IMAEs). Exploratory endpoints included objective response rate, progression-free survival, and overall survival. RESULTS: Ninety-seven patients had advanced predominantly ccRCC; 75.3% received only 1 prior systemic regimen in the advanced/metastatic setting. After a median follow-up of 17 months (range, 0.4-26.9 months), no grade 5 IMAEs occurred, and 9.3% of patients reported grade 3/4 IMAEs (hepatitis, 4.1%; diabetes mellitus, 2.1%; nephritis and renal dysfunction, 1.0%; rash, 1.0%; adrenal insufficiency, 1.0%). The objective response rate was 22.7% (95% confidence interval [CI], 14.8%-32.3%). Three patients had a complete response; 19 had partial responses. The median progression-free survival was 3.6 months (95% CI, 2.0-5.5 months). The median overall survival was 21.8 months (95% CI, 17.4 months to not estimable). CONCLUSIONS: This study validates the safety and efficacy of nivolumab 240 mg Q2W flat-dose monotherapy for previously treated advanced ccRCC and adds to previous safety and efficacy data using the 3 mg/kg Q2W dose.
Authors: Robert J Motzer; Toni K Choueiri; David F McDermott; Thomas Powles; Yann-Alexandre Vano; Saurabh Gupta; Jin Yao; Celine Han; Ron Ammar; Simon Papillon-Cavanagh; Shruti S Saggi; M Brent McHenry; Petra Ross-Macdonald; Megan Wind-Rotolo Journal: J Immunother Cancer Date: 2022-03 Impact factor: 12.469
Authors: Neal D Shore; François Laliberté; Raluca Ionescu-Ittu; Lingfeng Yang; Malena Mahendran; Dominique Lejeune; Louise H Yu; Joseph Burgents; Mei Sheng Duh; Sameer R Ghate Journal: Adv Ther Date: 2021-07-19 Impact factor: 3.845