Cabozantinib Plus Nivolumab in Patients with Non-Clear Cell Renal Cell Carcinoma: Updated Results from a Phase 2 Trial

Abstract

Treatment options are limited for patients with non-clear cell renal cell carcinoma (nccRCC). Patients with nccRCC experienced a favorable objective response rate (ORR) in a phase 2 trial of cabozantinib plus nivolumab. We now report updated efficacy and safety results at median follow-up of 34 mo for patients with papillary, unclassified, or translocation-associated RCC. Cabozantinib and nivolumab were administered at standard doses to patients with metastatic nccRCC that had progressed on zero or one line of systemic therapy. The primary endpoint was the ORR according to Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Forty patients were treated. At median follow-up of 34 mo for survivors, the ORR was 48% (95% confidence interval [CI] 31.5-63.9%). Median PFS was 13 mo (95% CI 7-16); the 12-mo and 24-mo PFS rates were 51% (95% CI 34-65%) and 23% (95% CI 11-37%), respectively. Median OS was 28 mo (95% CI 23-43); the 18-mo and 36-mo OS rates were 70% (95% CI 53-82%) and 44% (95% CI 28-60%), respectively. No new safety signals were seen with cabozantinib and nivolumab. This extended follow-up analysis demonstrates promising efficacy, and highlights the potential for sustained responses with cabozantinib plus nivolumab in patients with metastatic nccRCC.

Keywords: Cabozantinib; Immunotherapy; Kidney cancer; Nivolumab; Non–clear cell renal cell carcinoma; Tyrosine kinase inhibitor.

Fig. 1 –

Survival outcomes. (A) Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors v1.1. There were 33 PFS events (28 progression and 5 deaths with no progression). Median PFS was 13 mo (95% confidence interval [CI] 7–16). The PFS rate is 51% (95% CI 34–65%) at 12 mo and 23% (95% CI 11–37%) at 24 mo. (B) Overall survival (OS). There were 27 deaths in the 40-patient cohort. Median follow-up for survivors was 34 mo (range 20–51). Median OS was 28 mo (95% CI 23–43). The OS rate is 70% (95% CI 53–82%) at 18 mo and 44% (95% CI 28–60%) at 36 mo. (C) Median duration of response among responders, calculated using the Kaplan-Meier method from the time of response to progression/death or the last negative scan for censored observations. Of 19 patients with a complete or partial response, 14 experienced progression or death after their response and five were alive and progression-free at the time of last radiologic assessment. The median duration of response among responders was 16.5 mo (96% CI 9.7–19.8).

Fig. 1 –

Survival outcomes. (A) Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors v1.1. There were 33 PFS events (28 progression and 5 deaths with no progression). Median PFS was 13 mo (95% confidence interval [CI] 7–16). The PFS rate is 51% (95% CI 34–65%) at 12 mo and 23% (95% CI 11–37%) at 24 mo. (B) Overall survival (OS). There were 27 deaths in the 40-patient cohort. Median follow-up for survivors was 34 mo (range 20–51). Median OS was 28 mo (95% CI 23–43). The OS rate is 70% (95% CI 53–82%) at 18 mo and 44% (95% CI 28–60%) at 36 mo. (C) Median duration of response among responders, calculated using the Kaplan-Meier method from the time of response to progression/death or the last negative scan for censored observations. Of 19 patients with a complete or partial response, 14 experienced progression or death after their response and five were alive and progression-free at the time of last radiologic assessment. The median duration of response among responders was 16.5 mo (96% CI 9.7–19.8).