zanzalintinib (XL092) / Exelixis - LARVOL DELTA

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

LITESPARK-034: phase 3 study of belzutifan plus zanzalintinib versus belzutifan in participants with advanced renal cell carcinoma (RCC) during or after anti–PD-(L)1 therapy and VEGF-TKI (ESMO 2026) - No abstract available

Metastases • P3 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Zanzalintinib (XL092) in clear cell renal cell carcinoma (ccRCC): Results from STELLAR-001 (IKCS 2023) - No abstract available

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

Zanzalintinib in combination with immune checkpoint inhibitors: Design of the renal cell carcinoma expansion stage cohorts in STELLAR-002 (KCRS 2023) - "Zanzalintinib (XL092) is a novel, potent, orally bioavailable small molecule inhibitor of several receptor tyrosine kinases, including VEGFR2, MET, and the TAM kinases AXL, and MER. These receptor tyrosine kinases are implicated in several oncogenic processes, including tumor angiogenesis, proliferation, invasion, and metastasis."

Checkpoint inhibition • Combination therapy • Genito-urinary Cancer • Immune Modulation • Oncology • Renal Cell Carcinoma • Solid Tumor

Zanzalintinib (zanza) + nivolumab (nivo) ± relatlimab (rela) in patients (pts) with previously untreated clear cell renal cell carcinoma (ccRCC): Results from an expansion cohort of the phase 1b STELLAR-002 study. (ASCO 2025) - P1 | "First-line zanza had acceptable tolerability in combination with nivo or nivo/rela with a low rate of PPE; zanza+nivo showed promising preliminary activity in pts with adv/met ccRCC."

Clinical • P1 data • Clear Cell Renal Cell Carcinoma • Dermatology • Genito-urinary Cancer • Hypertension • 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

The U.S. Food and Drug ‌Administration has extended the ‌review of Exelixis’ experimental colorectal ​cancer drug combination by three months, the company said in a filing ‌on Friday. (Yahoo Finance) - "The ⁠regulator will now make its decision by ⁠March 3, 2027. In response to an FDA ​information request, ​Exelixis ​submitted updated safety ‌and efficacy data, which the health regulator classified as a major amendment, the filing showed. The company ‌is seeking approval ​for ​zanzalintinib, ​in combination with Roche's ‌immunotherapy Tecentriq for ​the ​treatment of subset of adult patients with metastatic ​colorectal ‌cancer."

PDUFA • Colorectal Cancer

Zanzalintinib (XL092) plus nivolumab in non-clear cell renal cell carcinoma: The randomized phase 3 STELLAR-304 study. (ASCO 2024) - P3 | "Sunitinib, a tyrosine kinase inhibitor (TKI), is a commonly used therapy for nccRCC based on clinical benefit demonstrated in phase 2 trials. The secondary endpoint is OS; safety will also be assessed. STELLAR-304 is currently recruiting patients in Europe, North and South America, and the Asia-Pacific region."

Clinical • P3 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Medullary Carcinoma • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • AXL

STELLAR-303: A phase 3 study of XL092 in combination with atezolizumab versus regorafenib in patients with previously treated metastatic colorectal cancer (mCRC). (ASCO-GI 2023) - P3 | "Regorafenib or trifluridine-tipiracil are approved for patients in the third- or later-line setting, but survival benefit is limited. While immune checkpoint inhibitor (ICI) therapy is approved (nivolumab ± ipilimumab, and pembrolizumab) in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) mCRC, the MSI-H phenotype is limited to ~5% of mCRC patients. In phase 1/2 trials, ICIs in combination with VEGFR2 multi-kinase inhibitors (MKIs) have demonstrated encouraging clinical activity in mCRC, including atezolizumab and durvalumab (ICIs) in combination with the MKI cabozantinib, with data suggesting a greater benefit in RAS wild-type (wt) vs mutant (mut) disease (Abrams TA, et al...Enrollment is ongoing. Clinical trial information: NCT05425940."

Clinical • Combination therapy • IO biomarker • Metastases • P3 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • AXL • MSI • PD-1 • PD-L1

A multicohort phase 1b study (STELLAR-002) of XL092 in combination with immunotherapy in patients with advanced solid tumors (SITC 2022) - P1 | "STELLAR-002 will evaluate the safety and clinical activity of XL092 alone and in combination with nivolumab ± ipilimumab in patients with advanced solid tumors. Trial Registration Trial registry is ClinicalTrials.gov NCT05176483 Ethics Approval The study will adhere to the principles outlined in ”Guideline for Good Clinical Practice” (GCP) and remain consistent with the most recent version of the Declaration of Helsinki. Consent Patients will be required to provide written informed consent."

Clinical • Combination therapy • P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer • AXL • KDR

LITESPARK-033: Phase 3 study of belzutifan plus zanzalintinib versus cabozantinib for recurrent clear cell renal cell carcinoma during or after adjuvant anti–PD-(L)1 therapy. (ASCO 2026) - P3 | "Clinical Trial Registration Number: NCT07227402 Background: Adjuvant pembrolizumab is standard of care for patients with renal cell carcinoma (RCC) at increased risk for recurrence after nephrectomy...Secondary end points are objective response rate and duration of response per RECIST v1.1 as assessed by BICR, and safety. The study is open and currently enrolling as of November 26, 2025."

Clinical • P3 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Sarcoma • Solid Tumor • AXL

Zanzalintinib for Advanced Urothelial Carcinoma Progressing After Prior Therapy (clinicaltrials.gov) - P2 | N=44 | Not yet recruiting | Sponsor: Guru Sonpavde | Initiation date: Jun 2026 ➔ Oct 2026

Trial initiation date • Oncology • Solid Tumor • Urothelial Cancer

Biomarker-Guided Treatment Selection in Metastatic Colorectal Cancer: A Critical Review of Established and Emerging Therapies. (PubMed, Crit Rev Oncol Hematol) - "In dMMR/MSI-H mCRC, immune checkpoint inhibition is the established first-line standard, with pembrolizumab and nivolumab plus ipilimumab producing durable disease control...For BRAF V600E-mutant disease, encorafenib plus cetuximab with fluoropyrimidine-based chemotherapy is a first-line standard. HER2-directed therapy with tucatinib plus trastuzumab or trastuzumab deruxtecan and combined KRAS G12C and EGFR inhibition are established after prior treatment but are not approved in the first-line setting...In previously treated non-MSI-H/dMMR mCRC, STELLAR-303 was the first phase 3 trial to demonstrate a significant overall survival benefit with an immune checkpoint inhibitor-containing regimen, zanzalintinib plus atezolizumab. Other investigational strategies include additional immunotherapy combinations, EGFR-MET bispecific antibody therapy with amivantamab, T-cell-engaging bispecific antibodies, therapeutic cancer vaccines, cellular therapies, and microbiome-directed..."

Biomarker • IO biomarker • Journal • Review • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • BRAF • KRAS • MSI • NTRK • RET

STELLAR-304: a phase III study of zanzalintinib (XL092) plus nivolumab in advanced non-clear cell renal cell carcinoma. (PubMed, Future Oncol) - P3 | "STELLAR-304 is a phase III trial evaluating first-line zanzalintinib plus nivolumab versus sunitinib in advanced nccRCC. Secondary endpoint is overall survival. To our knowledge, STELLAR-304 is the first phase III study assessing a TKI-ICI combination in nccRCC patients across multiple subtypes.Clinical Trial Registration: This trial is registered at ClinicalTrials.gov (identifier: NCT05678673)."

Clinical • Journal • P3 data • Genito-urinary Cancer • Non Clear Cell Renal Cell Carcinoma • Oncology • Solid Tumor

STELLAR-304: A randomized phase III study of zanzalintinib (XL092) and nivolumab in non-clear cell renal cell carcinoma (nccRCC) (ESMO 2023) - P3 | "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 • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Medullary Carcinoma • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • AXL • KDR

Maintenance zanzalintinib with oral etoposide following high-dose chemotherapy in patients with relapsed metastatic germ-cell tumor (GCT). (ASCO-GU 2026) - P1/2 | "Background: While most patients (pts) with metastatic GCTs are cured with first line cisplatin-based chemotherapy, 20-30% relapse after treatment. This study is currently enrolling patients. Clinical trial information: NCT06937866."

Clinical • Metastases • Genito-urinary Cancer • Germ Cell Tumors • Oncology • Testicular Cancer • AXL • KDR • MET

Zanzalintinib in Combination With Ipilimumab and Nivolumab in Patients With Metastatic Soft Tissue Sarcoma (clinicaltrials.gov) - P1 | N=18 | Suspended | Sponsor: Washington University School of Medicine | Recruiting ➔ Suspended

Trial suspension • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Contribution of atezolizumab (atezo) to the efficacy of the zanzalintinib (zanza) + atezo combination in patients (pts) with previously treated metastatic colorectal cancer (mCRC): Evidence from the phase 3 STELLAR-303 trial. (ASCO 2026) - P3 | "In STELLAR‑303, zanza + atezo significantly improved overall survival (OS) versus regorafenib (rego) in pts with previously treated mCRC. Zanza + atezo demonstrated PFS and OS benefit regardless of atezo TEADA status, with greater efficacy observed in TEADA-negative pts. ER analyses showed that higher atezo serum trough concentrations were associated with longer PFS and OS. These results support the contribution of atezo to the survival benefits observed with the zanza + atezo combination in pts with mCRC in the STELLAR-303 trial."

Clinical • Metastases • P3 data • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • AXL • MSI

EXACT: A Randomized phase II trial of XL092 (Zanzalintinib) in combination with immunotherapy in patients who progress on Adjuvant therapy in Clear Cell RCC [NCT06863311] (KCRS 2025) - P2 | "The EXACT Trial seeks to determine if Zanzalitinib and Zanzalitinib plus Nivolumab are effective treatments in patients who progress on adjuvant pembrolizumab. Trial Schema This study is in collaboration with Exelixis Inc."

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

STELLAR-201: a single-arm, multicenter, open‑label, phase 2 study of zanzalintinib in patients with recurrent or progressive meningioma (SNO 2026) - No abstract available

Clinical • P2 data • Brain Cancer • Meningioma • Solid Tumor

Phase II trial of zanzalintinib (XL-092) in combination with durvalumab and tremelimumab in unresectable hepatocellular carcinoma (ZENOBIA). (ASCO 2025) - P2 | "A Phase II study (CHECKMATE 040) reported an impressive objective response rate (ORR) of 29% with the combination of ipilimumab/nivolumab and Cabo but noted high toxicity rates...Comprehensive translational analyses include bulk RNA sequencing, spatial transcriptomics of baseline tumor biopsies, & serial ctDNA monitoring. Trial enrollment commenced in December 2024."

Combination therapy • P2 data • Gastroenterology • Gastrointestinal Disorder • Hepatocellular Cancer • Immunology • Oncology • Solid Tumor • AXL

STELLAR-316: Zanzalintinib Alone or in Combination With Pembrolizumab and Berahyaluronidase Alfa in Participants With Colorectal Cancer With Molecular Residual Disease (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Exelixis | Not yet recruiting ➔ Recruiting

Enrollment open • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

Zanzalintinib (zanza) + nivolumab (nivo) ± relatlimab (rela) in patients (pts) with advanced solid tumors: Results from two dose-escalation cohorts of the phase 1b STELLAR 002 study. (ASCO 2025) - P1 | "The tolerability of zanza + nivo and zanza + nivo/rela was manageable and consistent with each monotherapy agent. Preliminary safety, PK, and response data support selection of the 100-mg zanza dose in combination with nivo or nivo/rela for further investigation. Expansion cohorts are ongoing in various tumor types."

Clinical • Metastases • P1 data • Colorectal Cancer • Dermatology • Fatigue • Genito-urinary Cancer • Hypertension • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

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 | Sponsor: UNC Lineberger Comprehensive Cancer Center | Initiation date: Jun 2026 ➔ Sep 2026

Trial initiation date • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

A phase II trial of neoadjuvant zanzalintinib (ZANZA) plus nivolumab (NIVO) in patients with locally advanced and/or surgically challenging clear cell renal cell carcinoma (EXPLORE-RCC). (ASCO 2026) - P2 | "Key secondary/exploratory endpoints include efficacy outcomes (conversion to operable, disease free survival, overall survival, pathologic response), safety, surgery-related complications (including Clavien-Dindo), and biomarker correlatives. The trial is actively enrolling (ClinicalTrials.gov NCT06794229) at UT Southwestern and opening at Ohio State, Fox Chase Cancer Center, Virginia Commonwealth, Northwestern University, and Washington University in St Louis."

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