ASCO 2023: Nivolumab plus Cabozantinib in Patients with Non-Clear Cell Renal Cell Carcinoma: Updated Results from a Phase 2 Trial

(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a kidney and bladder cancers poster session. Dr. Chung-Han Lee presented updated results of CaboNivo, a phase 2 trial evaluating combination of nivolumab plus cabozantinib in patients with non-clear cell renal cell carcinoma (RCC).


Identification of effective systemic therapy options for non-clear cell renal cell carcinoma (RCC) remains an unmet clinical need. The CaboNivo trial evaluated the combination of cabozantinib 40 mg once daily plus nivolumab 240 mg once every 2 weeks or 480 mg once every 4 weeks in two cohorts of patients:

  • Cohort 1: Papillary, unclassified without papillary features, or translocation-associated RCC (n=40)
  • Cohort 2: Chromophobe RCC (n=7)  Closed early due to lack of efficacy

All patients were either treatment-naïve or had received one prior line of systemic therapy, excluding prior immune checkpoint inhibitors.

At a median follow-up of 13.1 months, the objective response rate (ORR) was 48% in Cohort 1, with a median progression-free survival (PFS) of 12.5 months and overall survival (OS) of 28 months.1 No responses were observed in Cohort 2.

The objective of this analysis was to provide an updated report of the CaboNivo trial with extended follow-up.

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This analysis included only patients from cohort 1 (n=40). Median follow-up time was 34 months (data cut-off: Dec 13, 2022). Twenty-six patients (65%) were previously untreated, and 14 (35%) had one prior treatment line: 10 (25%) received prior VEGF-targeted therapy and 8 (20%) received prior mTOR-targeted therapy. 

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The ORR remained 48% (95% CI: 32 – 64%), with a median duration of response of 17 months.

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The median PFS was 13 months (95% CI: 7 – 16). PFS at 12 and 24 months were 51% and 23%, respectively. The median OS was 28 months (95% CI: 23- 43%), with 18- and 36-months rates of 70% and 44%, respectively.

 

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Next, the investigators evaluated outcomes by prior treatments and histologic subtypes. The ORR was 54% in treatment-naïve patients (CR: 4%; PR: 50%), compared to 36% in patients who had received 1 prior line of therapy (no CRs). PFS and OS were similar across both groups. Similar ORRs were observed across all three histologic subtypes (papillary, unclassified without papillary features, translocation-associated).

Adverse events of any grade were experienced by 35 patients (88%); grade 3/4 adverse events were experienced by 22 patients (55%). Grade 3/4 AST and ALT elevations occurred in 18% and 23% of patients, respectively. Other common grade 3/4 adverse events were hypertension (5, 13%) and pain (4, 10%). The study therapy was discontinued in nine patients (28%) for toxicity.

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The investigators concluded that these updated results with extended follow-up highlight the efficacy and safety of combination of cabozantinib plus nivolumab in metastatic non-clear cell RCC patients with papillary, unclassified, or translocation associated histologies.

Presented by: Chung-Han Lee, MD, PhD, Medical Oncologist, Assistant Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023. 

References:

  1. Lee C, Voss MH, Carlo MI, et al. Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. J Clin Oncol, 2022;40(21):2333-2341.