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PURPOSE COSMIC-021 is evaluating cabozantinib plus atezolizumab in patients with solid tumors. We report results from patients with advanced clear cell (cc) and non–clear cell (ncc) renal cell carcinoma (RCC). METHODS This phase Ib study ( NCT03170960 ) enrolled patients age ≥ 18 years with advanced RCC. A dose-escalation stage was followed by expansion cohorts. For cohort expansion, prior systemic therapy was not permitted for ccRCC but allowed for nccRCC. Patients received oral cabozantinib 40 mg once a day (ccRCC and nccRCC) or 60 mg once a day (ccRCC only) plus atezolizumab (1,200 mg intravenously, once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1; the secondary end point was safety. RESULTS A total of 102 patients were enrolled. Median follow-up was 25.8, 15.3, and 13.3 months for the 40-mg ccRCC, 60-mg ccRCC, and nccRCC groups, respectively. ORR was 53% (80% CI, 41 to 65) in the 40-mg ccRCC group (n = 34) and 58% (80% CI, 46 to 70) in the 60-mg ccRCC group (n = 36), 3% and 11%, respectively, with complete response; median progression-free survival (exploratory end point) was 19.5 and 15.1 months, respectively. In nccRCC (n = 32), ORR was 31% (80% CI, 20 to 44), all partial responses; median progression-free survival was 9.5 months. Grade 3 or 4 treatment-related adverse events (TRAEs) were reported by 71% of patients in the 40-mg ccRCC group, 67% in the 60-mg ccRCC group, and 38% in the nccRCC group; TRAEs leading to discontinuation of both agents occurred in 15%, 6%, and 3% of patients, respectively. There were no grade 5 TRAEs. CONCLUSION The novel combination of cabozantinib plus atezolizumab demonstrated encouraging clinical activity and acceptable tolerability in patients with advanced ccRCC and nccRCC. Disease control was observed across dose levels and histologic subtypes.

BackgroundSystemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow‐growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature.MethodsThis was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient‐related outcomes. Wilcoxon 2‐sample rank‐sum tests and χ2 tests were used to assess differences between ST and AS cohorts in continuous and categorical variables, respectively. Kaplan‐Meier survival curves were used to assess survival.ResultsOf 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25‐44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST.ConclusionsAS occurs frequently (32%) in real‐world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients.

617 Background: Over the past decade, seven agents were approved for metastatic renal cell carcinoma (mRCC) leading to a rapidly evolving clinical landscape. Clinical trials addressing treatment efficacy, sequencing, and other questions may continue to impact management decisions. Furthermore, our prior retrospective experience indicates a significant proportion of pts may not receive systemic therapy in the first year after diagnosis with metastatic disease. This analysis describes contemporary patterns of care in the first 109 real world pts enrolled in a multicenter, prospective, observational registry. Methods: MaRCC Registry will enroll 500 pts from up to 60 US academic (ACAD) and community (COMM) sites with ~2 years of recruitment and ≥ 3 years of follow-up. Key inclusion criteria are age ≥ 18 years and diagnosis of mRCC with no prior systemic therapy (STx) for mRCC at study entry. Pts currently not on STx but who are being observed are permitted. Key endpoints include descriptive characteristics of treatments (e.g. treatment agents, sequence, duration, reasons for therapy choice and discontinuation), treatment effectiveness (e.g. overall response rate, progression free survival, overall survival), quality of life (PROs), medication adherence, and health resource utilization. Results: At data cutoff, 105 pts have been accrued with known STx status; median age 64 (Q1-3 range, 56-70); 66% male; 75% ACAD; 87% clear cell histology; and 31% stage IV at diagnosis. Initial management strategies are shown in the table. The initial management decision after accrual was to defer systemic therapy (Def STx) in 40% (N=44). In ACAD and COMM sites, Def STx percentages were 38% and 48% respectively. Baseline demographics and clinical characteristics were not notably different between Def STx pts and those treated with STx. Conclusions: In our prospective registry, we have identified a large percentage of pts who initially received Def STx. In the context of contemporary pts undergoing investigational and standard of care STx, we will describe the management and outcomes of the Def STx population. [Table: see text]