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DRUG:

zanzalintinib (XL092)

i
Other names: XL092, XL-092, XL 092
Associations
Company:
Exelixis
Drug class:
c-MET inhibitor, Tyrosine kinase inhibitor, VEGFR-1 antagonist
Related drugs:
Associations
3d
STELLAR-001: A Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors (clinicaltrials.gov)
P1, N=325, Active, not recruiting, Exelixis | Trial completion date: Nov 2024 --> May 2027 | Trial primary completion date: Nov 2024 --> Aug 2026
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability)
|
BRAF V600E • HR positive • MSI-H/dMMR • BRAF V600 • KRAS wild-type • RAS wild-type • NRAS wild-type
|
Tecentriq (atezolizumab) • Bavencio (avelumab) • zanzalintinib (XL092)
22d
XL092 (Zanzalintinib) for the Treatment of Patients With Metastatic or Unresectable Leiomyosarcoma (clinicaltrials.gov)
P2, N=29, Recruiting, Northwestern University | Not yet recruiting --> Recruiting
Enrollment open • Metastases
|
zanzalintinib (XL092)
2ms
Enrollment closed • Enrollment change • Metastases
|
Opdivo (nivolumab) • casdatifan (AB521) • zanzalintinib (XL092)
3ms
New P2 trial • Metastases
|
zanzalintinib (XL092)
3ms
New P2 trial • Metastases
|
zanzalintinib (XL092)
4ms
STELLAR-303: randomized phase III study of zanzalintinib + atezolizumab in previously treated metastatic colorectal cancer. (PubMed, Future Oncol)
Presented is the design of STELLAR-303, a global, phase III, open-label, randomized study evaluating zanzalintinib plus atezolizumab versus regorafenib in patients with non-MSI-H mCRC who progressed during/after or are refractory/intolerant to standard-of-care therapy. The primary end point is overall survival in patients without liver metastases.Clinical Trial Registration: NCT05425940 (ClinicalTrials.gov).
P3 data • Journal • Metastases
|
MSI (Microsatellite instability)
|
Tecentriq (atezolizumab) • Stivarga (regorafenib) • zanzalintinib (XL092)
4ms
Trial initiation date • Combination therapy • Metastases
|
PD-L1 (Programmed death ligand 1)
|
Keytruda (pembrolizumab) • zanzalintinib (XL092)
5ms
STELLAR-303: Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer (clinicaltrials.gov)
P3, N=874, Active, not recruiting, Exelixis | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
|
MSI (Microsatellite instability)
|
Tecentriq (atezolizumab) • Stivarga (regorafenib) • zanzalintinib (XL092)
6ms
Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
P1/2, N=675, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Jun 2026 --> Sep 2025 | Recruiting --> Active, not recruiting | Trial completion date: Sep 2027 --> Nov 2026
Enrollment closed • Trial completion date • Trial primary completion date • Metastases
|
PD-L1 (Programmed death ligand 1)
|
Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • tiragolumab (RG6058) • camonsertib (RP-3500) • cibisatamab (RG7802) • ciforadenant (CPI-444) • zanzalintinib (XL092)
9ms
A Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors (clinicaltrials.gov)
P1, N=325, Active, not recruiting, Exelixis | Trial primary completion date: Nov 2023 --> Nov 2024
Trial primary completion date • Combination therapy • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability)
|
BRAF V600E • HR positive • MSI-H/dMMR • BRAF V600 • KRAS wild-type • RAS wild-type • NRAS wild-type
|
Tecentriq (atezolizumab) • Bavencio (avelumab) • zanzalintinib (XL092)
9ms
Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
P1/2, N=675, Recruiting, Hoffmann-La Roche | N=470 --> 675 | Trial completion date: Nov 2026 --> Sep 2027 | Trial primary completion date: Aug 2025 --> Jun 2026
Enrollment change • Trial completion date • Trial primary completion date • Metastases
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • tiragolumab (RG6058) • camonsertib (RP-3500) • cibisatamab (RG7802) • ciforadenant (CPI-444) • zanzalintinib (XL092)
10ms
Enrollment change • Metastases
|
MSI (Microsatellite instability)
|
MSI-H/dMMR • RAS mutation
|
Tecentriq (atezolizumab) • Stivarga (regorafenib) • zanzalintinib (XL092)
11ms
New P1/2 trial • Metastases
|
Opdivo (nivolumab) • casdatifan (AB521) • zanzalintinib (XL092)
11ms
Enrollment open • Trial completion date • Combination therapy • Metastases
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Keytruda (pembrolizumab) • zanzalintinib (XL092)
12ms
Zanzalintinib (XL092) plus atezolizumab versus regorafenib in previously treated MSS/MSI-low metastatic colorectal cancer (mCRC): The randomized phase 3 STELLAR-303 study. (ASCO-GI 2024)
Most recently, in the phase 3 LEAP-017 study of patients with non–MSI-high/mismatch repair deficient (dMMR) mCRC, although pembrolizumab + lenvatinib did not improve overall survival (OS) vs standard of care, subgroup analysis suggested the potential for clinical benefit in patients without LM (Kawazoe et al, ESMO-WCGI 2023)...Prior regorafenib, trifluridine/tipiracil, or PD-L1/PD-1 ICIs are not allowed...Enrollment is ongoing in the US, Europe, and Asia-Pacific region. Clinical trial information: NCT05425940.
Clinical • P3 data • Metastases
|
MSI (Microsatellite instability) • AXL (AXL Receptor Tyrosine Kinase) • PD-1 (Programmed cell death 1)
|
Keytruda (pembrolizumab) • Tecentriq (atezolizumab) • Lenvima (lenvatinib) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil) • zanzalintinib (XL092)
1year
Zanzalintinib (XL092) and nivolumab in non–clear cell renal cell carcinoma: The randomized phase 3 STELLAR-304 study (NCT05678673) (EMUC 2023)
Sunitinib is the only single-agent tyrosine kinase inhibitor (TKI) to have demonstrated a clinicalbenefit (vs everolimus) in a study population with a broad range of histologic subtypes of metastatic nccRCC (Armstrong et al. The secondary endpoint is OS; safety will also be assessed. Enrollment is ongoing, and patients will be recruited across sites inEurope, North and South America, and the Asia-Pacific region.
Clinical • P3 data
|
AXL (AXL Receptor Tyrosine Kinase)
|
Opdivo (nivolumab) • sunitinib • everolimus • zanzalintinib (XL092)
1year
A Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors (clinicaltrials.gov)
P1, N=325, Active, not recruiting, Exelixis | Recruiting --> Active, not recruiting | N=921 --> 325
Enrollment closed • Enrollment change • Combination therapy • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability)
|
BRAF V600E • HR positive • MSI-H/dMMR • BRAF V600 • KRAS wild-type • RAS wild-type • NRAS wild-type
|
Tecentriq (atezolizumab) • Bavencio (avelumab) • zanzalintinib (XL092)
1year
New P2/3 trial • Combination therapy • Metastases
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Keytruda (pembrolizumab) • zanzalintinib (XL092)
over1year
Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
P1/2, N=470, Recruiting, Hoffmann-La Roche | Trial completion date: Aug 2025 --> Nov 2026 | Trial primary completion date: Apr 2024 --> Aug 2025
Trial completion date • Trial primary completion date • Metastases
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • tiragolumab (RG6058) • Repatha (evolocumab) • camonsertib (RP-3500) • cibisatamab (RG7802) • ciforadenant (CPI-444) • zanzalintinib (XL092)
over1year
STELLAR-304: A randomized phase III study of zanzalintinib (XL092) and nivolumab in non-clear cell renal cell carcinoma (nccRCC) (ESMO 2023)
Sunitinib is the only TKI to have shown a clinical benefit (vs everolimus) in a broad range of histologic subtypes of metastatic nccRCC (Armstrong et al. The secondary endpoint is OS; safety will also be assessed. STELLAR-304 is currently recruiting patients in 29 countries in Europe, North and South America, and the Asia-Pacific region.
Clinical • P3 data
|
AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor)
|
Opdivo (nivolumab) • sunitinib • everolimus • zanzalintinib (XL092)
over1year
Combination therapy • Checkpoint inhibition
|
zanzalintinib (XL092)
over1year
Zanzalintinib (XL092) in combination with atezolizumab for previously treated metastatic colorectal cancer (ESMO-GI 2023)
Immune checkpoint inhibitor (ICI) therapy with nivolumab ± ipilimumab or single-agent pembrolizumab is approved in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) mCRC, which constitutes a small subgroup (∼5%) of the overall patient population...Phase 1/2 studies evaluating cabozantinib (an inhibitor of MET, AXL, and VEGFR2) in combination with atezolizumab and durvalumab have demonstrated encouraging clinical activity (Abrams TA, et al...Patients must have progressed during/after or be intolerant to SOC therapies for mCRC; prior regorafenib, trifluridine-tipiracil, or anti–PD-L1/PD-1 ICIs are not allowed...The primary endpoint is duration of overall survival and secondary endpoints include progression-free survival, objective response rate, and duration of response (all per RECIST v1.1 by investigator), as well as safety and tolerability. Enrollment is ongoing in 16 countries, located in North America, Europe, and Asia-Pacific regions.Clinical trial identification: NCT05425940.Editorial acknowledgement: Editorial assistance was provided by Fishawack Communications Inc., part of Fishawack Health, and funded by Exelixis, Inc.Legal entity responsible for the study: Exelixis, Inc.
Combination therapy • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
|
MSI (Microsatellite instability) • AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor)
|
RAS mutation • RAS wild-type
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Tecentriq (atezolizumab) • Yervoy (ipilimumab) • Imfinzi (durvalumab) • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib) • Lonsurf (trifluridine/tipiracil) • zanzalintinib (XL092)
almost2years
MODULE 2: Optimizing the Use of Immune Checkpoint Inhibitors in the Management of mCRC (ASCO-GI 2023)
This activity is supported by educational grants from Bayer HealthCare Pharmaceuticals, Exelixis Inc, Lilly, Natera Inc, and Seagen Inc. Key data informing the rational incorporation of pembrolizumab, nivolumab and nivolumab/ipilimumab for microsatellite instability-high/mismatch repair-deficient mCRC Early results with and ongoing investigation of immune checkpoint inhibitors in combination with other systemic approaches (eg, chemotherapy, targeted therapy) for MSI-H/dMMR advanced CRC Biologic rationale for the investigation of immune checkpoint inhibition for microsatellite-stable (MSS) mCRC Clinical activity and safety observed with cabozantinib in combination with anti-PD-1/PD-L1 antibodies among patients with MSS mCRC in early-phase trials (eg, COSMIC-021 cohort 16, CAMILLA cohort 2) Pharmacologic and pharmacodynamic comparison of cabozantinib and XL092 Design, eligibility and efficacy and safety endpoints for the Phase III STELLAR-303 trial comparing XL092/atezolizumab to regorafenib for relapsed/refractory (R/R) MSS mCRC Available data with and ongoing investigation of other immune checkpoint inhibitor-based strategies (eg, lenvatinib/pembrolizumab, regorafenib/pembrolizumab) for MSS mCRC Available data with and ongoing investigation of other immune checkpoint inhibitor-based strategies (eg, lenvatinib/pembrolizumab, regorafenib/pembrolizumab) for patients with MSS mCRC
Checkpoint inhibition
|
MSI (Microsatellite instability)
|
MSI-H/dMMR
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Tecentriq (atezolizumab) • Yervoy (ipilimumab) • Lenvima (lenvatinib) • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib) • zanzalintinib (XL092)
2years
Preclinical characterization of XL092, a novel receptor tyrosine kinase inhibitor of MET, VEGFR2, AXL, and MER. (PubMed, Mol Cancer Ther)
Additionally, XL092 promoted M2 to M1 repolarization of macrophages in vitro and inhibited primary human macrophage efferocytosis in a dose-dependent manner. In summary, XL092 was shown to have significant antitumor and immunomodulatory activity in animal models both alone and in combination with immune checkpoint inhibitors, supporting its evaluation in clinical trials.
Preclinical • Journal
|
CD8 (cluster of differentiation 8) • AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor) • CD4 (CD4 Molecule)
|
zanzalintinib (XL092)
2years
Enrollment change • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability)
|
BRAF V600E • HR positive • MSI-H/dMMR • BRAF V600 • KRAS wild-type • RAS wild-type • NRAS wild-type
|
Tecentriq (atezolizumab) • Bavencio (avelumab) • zanzalintinib (XL092)
over2years
New P3 trial
|
MSI (Microsatellite instability)
|
MSI-H/dMMR • RAS mutation
|
Tecentriq (atezolizumab) • Stivarga (regorafenib) • zanzalintinib (XL092)
almost3years
New P1 trial • Combination therapy
|
PD-L1 (Programmed death ligand 1)
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • bempegaldesleukin (NKTR-214) • zanzalintinib (XL092)
3years
Trial in progress: Phase 1 first-in-human study of XL092 administered alone or in combination with immune checkpoint inhibitors in patients with inoperable locally advanced or metastatic solid tumors (SITC 2021)
P1 | "Patients will receive escalating doses of XL092 alone or in combination with ICIs (atezolizumab 1200mg Q3W or avelumab 800mg Q2W). The study is open for enrollment. Trial Registration NCT03845166"
Checkpoint inhibition • Combination therapy • P1 data • Clinical
|
AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor)
|
HR positive
|
Tecentriq (atezolizumab) • Bavencio (avelumab) • zanzalintinib (XL092)
over3years
A Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors (clinicaltrials.gov)
P1, N=800, Recruiting, Exelixis | N=425 --> 800 | Trial completion date: May 2022 --> Nov 2024 | Trial primary completion date: May 2022 --> Nov 2023
Clinical • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
|
HR positive
|
Tecentriq (atezolizumab) • Bavencio (avelumab) • zanzalintinib (XL092)
4years
A Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors (clinicaltrials.gov)
P1, N=425, Recruiting, Exelixis | N=151 --> 425 | Trial completion date: Feb 2021 --> May 2022 | Trial primary completion date: Feb 2021 --> May 2022
Clinical • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • PD(L)-1 Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1)
|
HR positive
|
Tecentriq (atezolizumab) • Bavencio (avelumab) • zanzalintinib (XL092)