Zanzalintinib

TrialFetch AI summary: Adults (≥18) with metastatic or unresectable soft tissue sarcoma (RECIST-measurable, ECOG 0–1) who have progressed after 1–3 prior metastatic lines (ASPS allowed without prior refractoriness) and have had no prior PD-1/PD-L1/CTLA-4 therapy or zanzalintinib/cabozantinib. Treatment is oral zanzalintinib (XL092), a multikinase TKI targeting VEGFR2/MET/TAM (TYRO3/AXL/MER), combined with nivolumab (PD-1 inhibitor) plus ipilimumab (CTLA-4 inhibitor) induction, followed by maintenance nivolumab with ongoing daily zanzalintinib.

ClinicalTrials.gov ID: NCT06968988

TrialFetch AI summary: Adults with unresectable/metastatic leiomyosarcoma or adipocytic sarcoma (excluding pure WD LPS and low‑grade LMS), ECOG 0–1, after 1–4 prior lines receive eribulin (D1,8 q21d) plus oral zanzalintinib (XL092), a multi‑target TKI of VEGFR2/MET/TAM kinases aimed at anti‑angiogenic and immunomodulatory effects. Allows treated/stable brain mets; key exclusions include significant CV disease, bleeding risk, GI perforation risk, moderate–severe hepatic impairment, and prior zanzalintinib.

ClinicalTrials.gov ID: NCT06957431

TrialFetch AI summary: Enrolling adults with incurable recurrent/metastatic head and neck squamous cell carcinoma (ECOG 0–1, measurable disease), including previously untreated R/M disease only if PD-L1 CPS ≥1 or patients previously treated with anti–PD-(L)1 therapy (no PD-L1 restriction), excluding prior EGFR inhibitors/cetuximab or VEGFR-targeted therapy and >2 prior systemic lines in the R/M setting. Patients receive oral zanzalintinib (investigational multi-kinase TKI targeting VEGFR2, MET, and TAM kinases) daily plus pembrolizumab (anti–PD-1) and cetuximab (anti-EGFR) IV in 42-day cycles with dose escalation/expansion to define the RP2D.

ClinicalTrials.gov ID: NCT06912087

TrialFetch AI summary: Adults with unresectable or metastatic clear cell RCC (± sarcomatoid) that recurred during adjuvant anti–PD-(L)1 or within 24 months after completion, without prior VEGF/TKI or HIF-2α therapy, receive oral zanzalintinib (VEGFR2/MET/TAM multi-TKI) plus belzutifan (HIF‑2α inhibitor). Open-label, nonrandomized cohorts explore two zanzalintinib dose levels to assess safety and preliminary efficacy (ORR by BICR).

ClinicalTrials.gov ID: NCT07049926

TrialFetch AI summary: Single-arm study of zanzalintinib (XL092), an oral multikinase inhibitor of VEGFR2, MET, and TAM (TYRO3/AXL/MER), as first-line systemic therapy in adults with locally advanced or metastatic radioiodine-refractory differentiated thyroid cancer (papillary, follicular, oncocytic/Hürthle, or poorly differentiated) with RECIST-measurable disease and recent progression. Excludes prior systemic therapy in the RAI-refractory setting and patients with active brain mets or significant cardiovascular/GI risk; daily dosing in 21-day cycles until progression or toxicity.

ClinicalTrials.gov ID: NCT06959641

TrialFetch AI summary: Adults with well-differentiated (Grade 1–3) unresectable or metastatic pancreatic or extra-pancreatic NETs with recent RECIST-defined progression and no prior VEGFR TKI or mTOR inhibitor are randomized to zanzalintinib (XL092, an oral multi-kinase inhibitor of VEGFR2/MET/TAM) versus everolimus. Excludes NECs and select NET subtypes; primary endpoint is PFS by blinded central review.

ClinicalTrials.gov ID: NCT06943755

TrialFetch AI summary: Adults with advanced/metastatic clear cell RCC who progressed on or after adjuvant anti–PD-1/PD-L1 therapy (no prior systemic therapy otherwise) are randomized to zanzalintinib (XL092), an oral multi-targeted TKI of VEGFR2/MET/TAM kinases, versus XL092 plus nivolumab (PD-1 inhibitor). Key exclusions include untreated/unstable CNS mets and active autoimmune disease requiring immunosuppression.

ClinicalTrials.gov ID: NCT06863311

TrialFetch AI summary: Adults with recurrent high-grade uterine/endometrial cancers (FIGO grade 3 endometrioid, serous, mixed high-grade, or carcinosarcoma) after platinum, ECOG 0–2, measurable disease, and prior HER2- or immune-therapy as appropriate, receive paclitaxel plus zanzalintinib (XL092), an oral multi-targeted TKI inhibiting VEGFR2, MET, and TAM kinases, with maintenance zanzalintinib for responders/stable disease. Excludes prior TKIs/bevacizumab, uncontrolled CV disease, high-risk bleeding/GI conditions, and untreated/unstable CNS disease.

ClinicalTrials.gov ID: NCT06795009

TrialFetch AI summary: Adults with unresectable, systemic therapy–naïve HCC (ECOG 0–1, Child-Pugh A) receive triplet therapy with zanzalintinib (XL-092; oral multikinase TKI targeting VEGFR2/MET/TAM), durvalumab (PD-L1 inhibitor) every 4 weeks, and a single priming dose of tremelimumab (CTLA-4 inhibitor), with cohorts exploring sequencing (TKI lead-in vs immediate I/O). Excludes prior PD-1/PD-L1/CTLA-4 or MET/VEGFR TKIs, significant autoimmune disease, active viral hepatitis/HIV, and high bleeding risk; mandatory baseline tumor tissue required.

ClinicalTrials.gov ID: NCT06698250

TrialFetch AI summary: Adults with radiographic mCRPC who have progressed after 177Lu‑PSMA‑617 receive oral zanzalintinib (XL092) monotherapy once daily. XL092 is an investigational multikinase TKI targeting VEGFR2, MET, and TAM kinases (TYRO3/AXL/MER) to inhibit angiogenesis and tumor growth; primary endpoint is 16‑week disease control.

ClinicalTrials.gov ID: NCT06568562

TrialFetch AI summary: Adults with metastatic or unresectable leiomyosarcoma after at least two prior systemic regimens (≤2 prior TKIs), ECOG 0–1, receive oral zanzalintinib (XL092), a multi-kinase inhibitor of VEGFR2, MET, and TAM (TYRO3/AXL/MER), given continuously in 14‑day cycles until progression/toxicity. Key exclusions include prior XL092, significant cardiovascular/bleeding risk, unstable CNS disease, and concurrent oral anticoagulants.

ClinicalTrials.gov ID: NCT06571734