Section 3 of 6
Product information and disease description
72 evidence topics · 53 sources
Product description
Phase of product development
Regulatory submission: NDA submitted December 2025
Updated FDA target action date
Launch
No evidence found.
Product information
Generic, brand name and therapeutic class of product
Manufacturer, compound identifier, and drug class
Dosage forms and strengths
Investigational tablet formulation and strengths
| Registry field | Quoted record |
|---|---|
| Pharmaceutical form | “Film-coated tablet” |
| Investigational salt | “XL092 hemifumarate” |
| Tablet strength, mg | “100” |
| Tablet strength, mg | “60” |
| Tablet strength, mg | “40” |
Commercial formulation
No evidence found.
Average sales price and wholesale acquisition cost
Not applicable.
American hospital formulary service (AHFS), or other drug classification
Receptor tyrosine kinase inhibitor classification
Indication
Proposed indication and prior treatment requirements
Pharmacology
Mechanism of action
Pharmacodynamics
Preclinical VEGFR2 phosphorylation in murine lungs
Pharmacokinetics
Preliminary median terminal half-life
Contraindications/Warnings/Precautions/Adverse effects
Warnings and precautions
Not applicable.
Special populations
STELLAR-303 protocol exclusion: pregnancy and lactation
Approved special-population dosing instructions
No evidence found.
Drug/Drug, drug/disease interactions
Effects of other drugs on Zanzalintinib
No evidence found.
Effects of Zanzalintinib on other drugs
No evidence found.
Dosing and administration
Dosage
STELLAR-303 investigational dosing and administration
| Trial arm | Direct quotation |
|---|---|
| Zanzalintinib plus atezolizumab | “XL092 100 mg PO QD + atezolizumab 1200 mg IV Q3W” |
| Regorafenib | “regorafenib 160 mg PO QD (21 days/28-day cycle)” |
Administration
Registry route of zanzalintinib administration
Access and distribution
Commercial distribution arrangements and zanzalintinib-specific patient assistance
No evidence found.
Co-prescribed/Concomitant therapies
Combination therapy in the submitted application
Effect of Zanzalintinib on quality measures
Product-specific effects on healthcare quality measures
No evidence found.
Product comparison
Related immunotherapy combinations: LEAP-017, lenvatinib plus pembrolizumab versus standard of care
Related immunotherapy combinations: IMblaze370, atezolizumab with or without cobimetinib versus regorafenib
Place of product in therapy
Disease description
Definition and etiology
Epidemiology
Incidence of Metastatic colorectal cancer
U.S. incidence, all colorectal cancer stages
Estimated U.S. new cases in 2026, all colorectal cancer stages
Distant-stage disease at diagnosis
| SEER measure | Direct quotation |
|---|---|
| Percentage diagnosed at distant stage | “23%” |
Prevalence of Metastatic colorectal cancer
U.S. prevalence in 2023, all colorectal cancer stages
Metastatic-specific prevalence
No evidence found.
Natural history, survival, and mortality
Distant-stage five-year relative survival
| SEER measure | Direct quotation |
|---|---|
| Distant-stage five-year relative survival | “16.9%” |
Estimated U.S. deaths in 2026, all colorectal cancer stages
| Measure | Quoted value |
|---|---|
| Deaths | “55,230” |
Pathophysiology
Diagnosis
Clinical presentation - signs and symptoms
Bowel symptoms: change in bowel habits
Bleeding: blood in the stool
Pain: persistent abdominal symptoms
Long-term morbidity
No evidence found.
Burden of Metastatic colorectal cancer
Humanistic burden and health-related quality of life
Comparator and disease-state studies: third-line treatment decision-making among community physicians
Comparator and disease-state studies: SUNLIGHT health-related quality of life and performance status
Comparator and disease-state studies: FRESCO-2 quality-adjusted survival
Economic burden and healthcare resource utilization
Metastatic colorectal cancer treatment costs: systematic review
Cost concentration in regimens containing biological agents
Major financial hardship in metastatic colorectal cancer
Comparator and disease-state studies: third-line treatment discontinuation and cost effectiveness
Economic impact of Metastatic colorectal cancer on families
Economic impact of diagnostic testing
KRAS and BRAF predictive testing before cetuximab: Swiss economic model
Approaches to treatment
Current treatment options and standard of care
Cytotoxic chemotherapy
First-line cytotoxic chemotherapy backbones
VEGF-pathway antibodies and fusion proteins
First-line bevacizumab with cytotoxic chemotherapy
Approved treatment alternatives: trifluridine/tipiracil plus bevacizumab
EGFR monoclonal antibodies
Biomarker-directed treatment recommendations
Population recommended for first-line anti-EGFR therapy plus doublet chemotherapy
Immune checkpoint inhibitors
Biomarker-directed treatment recommendations
Nivolumab plus ipilimumab: FDA-approved disease subgroup
VEGFR and multikinase inhibitors
Comparator pivotal publication: CORRECT overall survival
Comparator pivotal publication: CORRECT toxicity
BRAF-directed combination therapy
Encorafenib traditional approval: combination and biomarker requirements
HER2-directed therapy
Tucatinib with trastuzumab after prior chemotherapy
KRAS G12C-directed combination therapy
Sotorasib plus panitumumab: disease subgroup and prior therapy
NTRK inhibitors
Therapies recommended for an NTRK fusion
Surgical resection
Potentially curative liver-metastasis resection
Thermal ablation
Small liver metastases in selected unresectable or oligometastatic disease
Stereotactic body radiotherapy
Guideline-supported radiotherapy option
Intra-arterial therapies
Non-curative intra-arterial options in expert centres
Limitations of current therapies
Summary
Available treatments depend on molecular subtype, prior therapy, and resectability. ASCO recommends first-line pembrolizumab for MSI-H or dMMR disease but does not recommend anti-EGFR therapy for RAS-mutant disease. A systematic review of 53 clinical trials reported limited activity for checkpoint-inhibitor monotherapy or checkpoint-inhibitor combinations in MSS colorectal cancer. The LEAP-017 and IMblaze370 trials did not establish their specified overall-survival benefits. These findings limit extrapolation between biomarker groups and between different kinase-inhibitor and immunotherapy combinations.
Immune checkpoint inhibitors in microsatellite-stable colorectal cancer: systematic review
Place in treatment, anticipated use, and care setting
Summary
The proposed population comprises adults previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, with prior anti-EGFR therapy for RAS wild-type disease. The pivotal regimen combines daily oral zanzalintinib with intravenous atezolizumab every three weeks. This is an investigational treatment position, not an approved prescribing recommendation or established commercial access pathway.
Heterogeneity of treatment effect
STELLAR-303 overall-survival subgroup estimates at the initial reported analysis
| Subgroup | Hazard ratio and 95% confidence interval |
|---|---|
| RAS wild type | “0.79 (0.61-1.01)” |
| RAS mutant | “0.80 (0.66-0.98)” |
Final overall-survival analysis without active liver metastases
Care management intervention strategies
Shared decision making
Other product development or post-marketing obligations required by the FDA
Not applicable.
Ongoing post-approval monitoring
Not applicable.