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Therapeutics (Systemic- Radiation therapy, ablation, surgery, interventional radiology, urology, medical oncology)

1: Zanzalintinib (XL092) in clear cell renal cell carcinoma (ccRCC): Results from STELLAR-001

    Lead Author(s)

  • Sumanta Kumar Pal, MD

    Professor, Dept of Medical Oncology & Therapeutic Research
    City of Hope Comprehensive Cancer Center, Duarte, CA, USA
    Duarte, CA, United States

Background: Zanzalintinib (XL092) is a novel, multi-targeted TKI that targets VEGFR, MET, and TAM kinases. Here we present initial results of single-agent zanzalintinib in the ccRCC expansion cohort, including outcomes by prior exposure to cabozantinib.

Methods: Adult patients with advanced ccRCC and ECOG ≤1 were eligible following radiographic progression on ≥1 prior systemic therapy for inoperable, locally advanced or metastatic disease. Patients received zanzalintinib at a starting dose of 100 mg once daily. ORR by investigator per RECIST 1.1 and safety were evaluated.

Results: A total of 32 patients were enrolled in the ccRCC expansion cohort. Median follow-up was 7.0 months (range: 4.4–12.5). Median age was 64 (range 39–79) years, and 72% were male; 81% had IMDC intermediate-risk disease, and 6% had poor risk. Patients had received a median of 2 (range 1–3) lines of prior therapy. Fourteen (44%) patients had never received cabozantinib (cabo-naïve), and 17 (53%) received prior cabozantinib (cabo-exposed); cabozantinib exposure was unknown for 1 patient. In the cabo-exposed and cabo-naïve subgroups, 10/17 (59%) and 5/14 (36%) patients had ECOG 1, respectively, and 10/17 (59%) and 2/14 (14%) had ≥3 prior lines of therapy. At data cutoff, 18 (56%) patients remain on study treatment. With a best response of 10 PRs and 18 SDs, the ORR was 31% and disease control rate (DCR) was 88%. In cabo-naïve and cabo-exposed patients, ORR was 43% and 24%, respectively; DCR was 86% and 94%. Two cabo-naïve patients who had unconfirmed PRs at data cutoff were subsequently confirmed to have PR (updated ORR 38% in the overall population and 57% in the cabo-naïve population).

Conclusions: Single-agent zanzalintinib showed promising preliminary antitumor activity and manageable toxicity in patients with previously treated advanced ccRCC. Antitumor activity was observed in both cabo-naïve and cabo-exposed patient populations, with most patients in both subgroups achieving disease control.