Breakthrough Clinical Results
Exelixis announced positive results from the Phase 1b/2 STELLAR-002 trial evaluating zanzalintinib in combination with immune checkpoint inhibitors for advanced kidney cancer. Data presented at ASCO 2025 showed an objective response rate of 63% and a disease control rate of 90% for zanzalintinib plus nivolumab in patients with previously untreated advanced clear cell renal cell carcinoma (RCC). Additional data from dose-finding cohorts were also presented, indicating a manageable toxicity profile. These findings suggest potential for zanzalintinib-based regimens in advanced solid tumors.
Key Highlights
- 63% objective response rate and 90% disease control rate observed with zanzalintinib plus nivolumab in advanced clear cell RCC.
- Data from multiple dose-escalation cohorts showed a manageable toxicity profile.
- Encouraging results support further evaluation of zanzalintinib-based regimens in advanced solid tumors.
- Results presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
Incidence and Prevalence
Global Incidence and Prevalence of Kidney Cancer
Kidney cancer represents a significant global health concern, accounting for approximately 2% of all cancers worldwide, with renal cell carcinoma being the most common form. Some sources indicate that renal cancer may represent up to 3% of all cancers globally.
Global Trends
The incidence and mortality rates of kidney cancer are increasing by 2-3% per decade globally. This is supported by additional data showing a 2% annual increase in incidence worldwide. The incidence of kidney cancer has increased worldwide in recent years, indicating a growing public health challenge.
Geographic Variations
There are notable geographic variations in kidney cancer distribution: - Kidney cancer is less common in Asia compared with the West - However, its incidence is increasing in more developed Asian nations - In the United States, more than 50,000 Americans were diagnosed with kidney and renal pelvis cancer in 2010
United States Specific Data
In the US, the renal cell carcinoma incidence rate increased from 10.6/100,000 individuals in 2001 to 12.4/100,000 in 2010. The incidence rate in men was almost double that in women.
Between 1975 and 1995, age-adjusted incidence rates for renal cell carcinoma were: - White men: 9.6 per 100,000 person-years - White women: 4.4 per 100,000 person-years - Black men: 11.1 per 100,000 person-years - Black women: 4.9 per 100,000 person-years
For renal pelvis cancer, the rates were: - White men: 1.5 per 100,000 person-years - White women: 0.7 per 100,000 person-years - Black men: 0.8 per 100,000 person-years - Black women: 0.5 per 100,000 person-years
Increasing Trends in the United States
Renal cell cancer incidence rates increased steadily between 1975 and 1995: - 2.3% annually among white men - 3.1% annually among white women - 3.9% annually among black men - 4.3% annually among black women
Risk Factors
Known risk factors for kidney cancer include: - Cigarette smoking - Obesity - Acquired cystic kidney disease - Inherited susceptibility
These risk factors may partially explain the rising global incidence rates as some factors like obesity become more prevalent worldwide.
Mechanism of Action
Three Most Common Mechanisms of Action in Trials for Unapproved Kidney Cancer Drugs
Based on the available information, the three most common mechanisms of action (MOAs) in trials for drugs that have not been approved for kidney cancer are:
1. HIF-2α inhibition
The hypoxia-inducible factor-2α (HIF-2α) inhibitor belzutifan is FDA approved for patients with von Hippel-Lindau disease and is currently being investigated in patients with nonhereditary renal cell carcinoma.
2. Glutamate synthesis inhibition
The glutamate synthesis inhibitor, telaglenastat, perhaps confers synergistic benefit when combined with everolimus, but combination with cabozantinib was not so effective.
3. Dual mTOR inhibition
Dual mammalian target of rapamycin (mTOR) inhibition with sapanisertib does not appear to be an effective therapeutic option.
These novel approaches are among those being investigated for managing advanced renal cell carcinoma with varying levels of success.
Drug used in other indications
Based on the provided context, there is no information available about clinical trials of Zanzalintinib and nivolumab for indications other than kidney cancer. In fact, the context does not mention "Zanzalintinib" at all.
The context only provides information about:
- Nivolumab being used in metastatic renal cell carcinoma patients with poor prognostic features
- Nivolumab showing activity in non-clear cell RCC subtypes, including unclassified, papillary and collecting duct subtypes
The context mentions lenvatinib (which is different from zanzalintinib) being approved for: - Radioiodine-refractory differentiated thyroid cancer (as monotherapy) - Advanced renal cell carcinoma (in combination with everolimus as second-line treatment) - Unresectable hepatocellular carcinoma (under investigation) - Endometrial carcinoma
Regarding intervention models for trials of zanzalintinib and nivolumab, the context provides no information about this topic.