zanzalintinib (XL092) / Exelixis - LARVOL DELTA

Zanzalintinib versus everolimus in patients with previously treated advanced neuroendocrine tumors: The phase 2/3, randomized STELLAR-311 trial. (ASCO-GI 2026) - P2/3 | "Funded by Exelixis, Inc. Clinical Trial Registration Number: NCT06943755 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Metastases • P2/3 data • Gastrointestinal Cancer • Oncology • Solid Tumor

A phase Ib/II study of zanzalintinib (XL092) in second line and beyond for the treatment of advanced hepatocellular carcinoma. (ASCO-GI 2026) - P1/2 | "Clinical Trial Registration Number: NCT07042919 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Metastases • P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Zanzalintinib: Initiation of trial STELLAR-201 trial for recurrent meningioma in H1 2026 (Exelixis, Inc) - R&D Day 2025: Initiation of trial STELLAR-316 trial for adjuvant ctDNA+ CRC in H2 2026

New trial • Colorectal Cancer • Gastrointestinal Cancer • Meningioma • Oncology

Zanzalintinib: "3L+ CRC Market Is Approaching ~$1.5B in 2026 and Represents Significant Opportunity for Zanzalintinib" (Exelixis, Inc) - R&D Day 2025

Commercial • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Zanzalintinib: "Median OS: Zanzalintinib + Atezolizumab: 10.9 months; Regorafenib: 9.4 months"; an OS benefit with zanzalintinib + atezolizumab vs. regorafenib was consistently observed across key subgroups"; Colorectal cancer (Exelixis, Inc) - R&D Day 2025

P3 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Dose Finding Study of Zanzalintinib With Pembrolizumab and Cetuximab in Head and Neck SCC (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: University of Chicago | Active, not recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Dr. @AnwaarSaeed3 presents STELLAR-303: Zanzalintinib + atezolizumab shows a significant OS benefit over regorafenib in chemorefractory, MSS mCRC—marking the first I/O-based phase 3 success in this population. @ecancer Watch on #Vumedi: https://tinyurl.com/42jxx89z #CRC #ESMO2025

Zanzalintinib plus atezolizumab versus regorafenib in refractory colorectal cancer (STELLAR-303): a randomised, open-label, phase 3 trial. (PubMed, Lancet) - P3 | "STELLAR-303 is the first phase 3 trial to show a significant improvement in overall survival with an immunotherapy-based regimen, zanzalintinib-atezolizumab, in patients with relapsed or refractory metastatic colorectal cancer that is not MSI-H or dMMR. This combination represents a chemotherapy-free treatment option with a novel mechanism of action for heavily pretreated patients in need of improved therapies."

Journal • P3 data • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI

Dr Saeed on the Rationale for Evaluating the Combination of Zanzalintinib Plus Atezolizumab vs Regorafenib in mCRC (OncLive) - "Anwar Saeed, MD...discussed the biological and clinical rationale supporting the phase 3 STELLAR-303 trial NCT05425940), which evaluated the combination of zanzalintinib, a next-generation multi–TKI plus atezolizumab (Tecentriq) vs regorafenib (Stivarga) in patients with previously treated metastatic colorectal cancer (mCRC)."

Video

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 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P3 trial • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

SINGLE-ARM, OPEN-LABEL PHASE II TRIAL OF XL092 (ZANZALINTINIB) IN PATIENTS WITH ADVANCED LEIOMYOSARCOMA: TRIAL IN PROGRESS (CTOS 2025) - "Approved subsequent line agents such as trabectedin and pazopanib have demonstrated short-term improvements in progression-free survival (PFS). This trial will evaluate the clinical activity and tolerability of XL092 in heavily pretreated LMS. A 6-month PFS of ≥50% would strongly support further investigation of XL092 in this population. Protocol is being amended to include a second cohort of translocation-associated sarcomas"

Clinical • Metastases • P2 data • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • AXL

Merck and Exelixis reveal their combo study (ApexOnco OncologyPipeline) - "Merck & Co has finally pulled back the curtain on its long-awaited phase 3 trial pairing Welireg against Exelixis’s Cabometyx follow-on zanzalintinib. The study, Litespark-033, has now landed on clinicaltrials.gov, and is set to kick off before the end of the year. This is the first of two phase 3 trials in renal cancer that the partners promised when they signed a deal last year, with silence still surrounding the second. Litespark-033 will evaluate the Welireg/zanzalintinib combo against Cabometyx in the post adjuvant PD-(L)1 setting, mirroring the indication explored in the phase 1/2 trial that started earlier this year."

Trial status • Renal Cell Carcinoma

Zanzalintinib for the Treatment of Advanced Thyroid Cancer Before Surgery (clinicaltrials.gov) - P2 | N=45 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Oct 2029 ➔ Oct 2030

Trial completion date • Oncology • Solid Tumor • Thyroid Gland Carcinoma

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=314 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2026 ➔ Nov 2025

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Maintenance Zanzalintinib and Durvalumab in Participants With Advanced Hepatocellular Cancer (clinicaltrials.gov) - P2 | N=16 | Not yet recruiting | Sponsor: Amit Mahipal

New P2 trial • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Maintenance Zanzalintinib With Etoposide After HDCT in GCT (clinicaltrials.gov) - P1/2 | N=38 | Recruiting | Sponsor: Indiana University | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2032 ➔ Sep 2031

Enrollment open • Trial completion date • Germ Cell Tumors

Zanzalintinib plus atezolizumab (zanza + atezo) vs regorafenib (rego) in patients (pts) with previously treated metastatic colorectal cancer (mCRC): Primary overall survival (OS) analysis from the randomized, open-label, phase III STELLAR-303 study (ESMO 2025) - P3 | "Conclusions Zanza + atezo significantly improved OS vs rego with no new safety signals, representing a potential new treatment option for pts with previously treated mCRC. The trial continues to the final OS analysis in the nlmITT population."

Clinical • Late-breaking abstract • Metastases • P3 data • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • AXL • MSI

ICI-Based Combo Prolonged Survival in Metastatic CRC (Cancer Therapy Advisor) - "'The combination of zanzalintinib-atezolizumab represents a potential novel and chemotherapy-free treatment option for heavily pretreated metastatic colorectal cancer patients in need of more improved therapy,' Dr. Saeed said."

Media quote

Primary OS analysis of Phase III STELLAR-303: zanza + atezo vs rego in previously treated mCRC (YouTube) - "Anwaar Saeed, MD...discusses the results of the STELLAR-303 study (NCT05425940), a Phase III trial evaluating zanzalintinib plus atezolizumab versus regorafenib in patients with previously treated mCRC, highlighting a significant overall survival (OS) advantage with the combination. Dr Saeed notes that the study demonstrates a 20% reduction in the risk of death with the combination, with a median OS of 10.9 months, compared to 9.4 months with regorafenib, and emphasizes the potential of this immunotherapy-based approach to change the treatment landscape for mCRC."

Video

STELLAR-303: Study of XL092 + Atezolizumab vs Regorafenib in Participants With Metastatic Colorectal Cancer (clinicaltrials.gov) - P3 | N=901 | Active, not recruiting | Sponsor: Exelixis | Trial completion date: Feb 2026 ➔ Jan 2027 | Trial primary completion date: Aug 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • MSI

EXPLORE-RCC: Neoadjuvant Zanzalintinib Plus Nivolumab in Patients With Locally Advanced and/or Inoperable Clear Cell Renal Cell Carcinoma With or Without Non-measurable Metastasis (clinicaltrials.gov) - P2 | N=69 | Recruiting | Sponsor: Qian Qin | Not yet recruiting ➔ Recruiting

Enrollment open • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Dose Finding Study of Zanzalintinib With Pembrolizumab and Cetuximab in Head and Neck SCC (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: University of Chicago | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Substudy 03C: A Study of Combination Therapies in Participants With Renal Cell Carcinoma With Recurrent Disease During or After Anti-PD-(L)1 Therapy (MK-3475-03C/KEYMAKER-U03) (clinicaltrials.gov) - P1/2 | N=140 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | N=100 ➔ 140

Enrollment change • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

STELLAR-311: A randomized phase 2/3 study of zanzalintinib versus everolimus in patients with previously treated advanced neuroendocrine tumors (NANETS 2025) - P2/3 | "BACKGROUND Targeted therapy options for patients with previously treated neuroendocrine tumors (NETs) include the mammalian target of rapamycin (mTOR) inhibitor everolimus and the vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) sunitinib and cabozantinib...RESULTS STELLAR-311 is open and enrolling patients. CONCLUSIONS N/A"

Clinical • Metastases • P2/3 data • Neuroendocrine Tumor • Oncology • Solid Tumor • AXL

EXPLORE-RCC: A phase II study of neoadjuvant zanzalintinib (ZANZA) plus nivolumab (NIVO) in patients with locally advanced and/or inoperable clear cell renal cell carcinoma (ccRCC) (ESMO 2025) - P2 | "Legal entity responsible for the study Hoosier Cancer Research Network. Funding Exelixis."

Clinical • Metastases • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor