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    DRUG:

    zanzalintinib (XL092)

    i
    Other names: XL092, XL-092, XL 092
    Associations

    News

    Trials
    Company:
    Exelixis
    Drug class:
    Tyrosine kinase inhibitor
    Related drugs:
    Associations

    News

    Trials
    3d
    Molecular complete response to the RIN protocol (regorafenib, ipilimumab, and nivolumab) in a patient with advanced recurrent metastatic mismatch repair proficient/microsatellite stable (pMMR/MSS) rectal cancer. (PubMed, Ther Adv Med Oncol)
    Rectal cancer recurrence remains a major therapeutic challenge, particularly in patients unresponsive to conventional regimens. While previous studies have demonstrated limited benefit of immunotherapy in this tumor subtype, the present findings suggest an emerging therapeutic opportunity that warrants prospective evaluation to confirm efficacy, explore the mechanistic basis, and identify biomarkers predictive of durable response beyond the absence of liver metastases. More effective combinatorial regimens like zanzalintinib and atezolizumb (STELLAR-303) trial, as well as newer generation of CTLA-4 inhibitors like botensilimab, vilastobart, and muzastotug are showing more promise for patients with MSS colorectal cancers in particular who do not have liver metastases (NLM).
    Journal • Mismatch repair • PD(L)-1 Biomarker • IO biomarker • pMMR
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    KRAS (KRAS proto-oncogene GTPase) • CEACAM5 (CEA Cell Adhesion Molecule 5)
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    KRAS mutation • KRAS G12D • KRAS G12
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    Opdivo (nivolumab) • Yervoy (ipilimumab) • Stivarga (regorafenib) • botensilimab (AGEN1181) • vilastobart (XTX101) • muzastotug (ADG126) • zanzalintinib (XL092)
    4d
    A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034) (clinicaltrials.gov)
    P3, N=758, Not yet recruiting, Merck Sharp & Dohme LLC
    New P3 trial
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    Welireg (belzutifan) • zanzalintinib (XL092)
    10d
    NEO COMBAT XL: H&N NEO-COMBAT XL: Neoadjuvant XL-092 (Zanzalintinib) and Pembrolizumab (Keytruda) in Surgically Resectable, HPV Negative Oral Cavity Squamous Cell Carcinoma (OCSCC) (clinicaltrials.gov)
    P2, N=26, Not yet recruiting, UNC Lineberger Comprehensive Cancer Center
    New P2 trial
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    PD-L1 (Programmed death ligand 1)
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    Keytruda (pembrolizumab) • zanzalintinib (XL092)
    12d
    LITESPARK-033: A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033) (clinicaltrials.gov)
    P3, N=904, Recruiting, Merck Sharp & Dohme LLC
    Trial initiation date
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    Cabometyx (cabozantinib tablet) • Welireg (belzutifan) • zanzalintinib (XL092)
    15d
    A Multi-Center Single-Arm Phase 2 Trial Of Zanzalintinib In Combination With Cemiplimab In BRAF Wild-Type Anaplastic Thyroid Cancer: The ZEPHYR Trial (clinicaltrials.gov)
    P2, N=12, Not yet recruiting, M.D. Anderson Cancer Center
    New P2 trial
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    PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene)
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    BRAF V600E • BRAF V600 • BRAF wild-type
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    Libtayo (cemiplimab-rwlc) • zanzalintinib (XL092)
    19d
    LITESPARK-033: A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033) (clinicaltrials.gov)
    P3, N=904, Recruiting, Merck Sharp & Dohme LLC
    Trial initiation date
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    Cabometyx (cabozantinib tablet) • Welireg (belzutifan) • zanzalintinib (XL092)
    29d
    A Phase 2 Trial of Zanzalintinib in Advanced/Metastatic Bone Sarcomas (ZAMBONE) (clinicaltrials.gov)
    P2, N=70, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting
    Enrollment open
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    zanzalintinib (XL092)
    1m
    A Study of Zanzalintinib in Participants With Recurrent or Progressive Meningioma (clinicaltrials.gov)
    P2, N=100, Not yet recruiting, Exelixis
    New P2 trial
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    zanzalintinib (XL092)
    1m
    A clinical study of belzutifan and zanzalintinib in people with advanced kidney cancer (MK-6482-033) (2024-517136-21-00)
    P2/3, N=398, Recruiting, Merck Sharp & Dohme LLC
    New P2/3 trial
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    Cabometyx (cabozantinib tablet) • Welireg (belzutifan) • zanzalintinib (XL092)
    1m
    XL092-311: A Phase 2/3 clinical trial with zanzalintinib versus everolimus (2025-521043-20-00)
    P2/3, N=172, Not yet recruiting, Exelixis Inc.
    New P2/3 trial
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    SSTR (Somatostatin Receptor)
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    SSTR positive
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    everolimus • zanzalintinib (XL092)
    1m
    Myeloid-derived suppressor cells and regulatory T cells in colorectal cancer: a synergistic immunosuppressive axis and emerging therapeutic opportunities. (PubMed, Front Immunol)
    Emerging clinical and translational data indicate that disrupting this axis can sensitize MSS-CRC to ICIs: for example, Zanzalintinib combined with Atezolizumab reported survival benefit in the STELLAR-303 trial, and dual blockade of novel checkpoints with PD-(L)1 has been associated with enhanced immune activation in solid tumors. Targeting the MDSC-Treg axis therefore represents a promising strategy to overcome immunotherapy resistance in MSS/pMMR CRC.
    Review • Journal
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    HIF1A (Hypoxia inducible factor 1, alpha subunit) • CD73 (5'-Nucleotidase Ecto) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • TLR4 (Toll Like Receptor 4) • CXCL3 (C-X-C Motif Chemokine Ligand 3)
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    Tecentriq (atezolizumab) • zanzalintinib (XL092)
    1m
    STELLAR-002: Study of Zanzalintinib in Combination With Immuno-Oncology Agents in Participants With Solid Tumors (clinicaltrials.gov)
    P1, N=1314, Recruiting, Exelixis | Active, not recruiting --> Recruiting
    Enrollment open
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    FH (Fumarate Hydratase)
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    PD-L1 expression
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    Opdivo (nivolumab) • Yervoy (ipilimumab) • relatlimab (BMS-986016) • zanzalintinib (XL092)