Exelixis Announces Landmark Five-Year Results from CheckMate -9ER Trial, Solidifying CABOMETYX and Opdivo as a Leading First-Line Treatment for Advanced Kidney Cancer
The landscape of advanced kidney cancer treatment is undergoing a major transformation as Exelixis, Inc. (Nasdaq: EXEL) unveils the final five-year results from the pivotal CheckMate -9ER trial. The long-term findings reaffirm the superior efficacy of CABOMETYX® (cabozantinib) in combination with Opdivo® (nivolumab) compared to sunitinib, providing a compelling survival benefit for patients with previously untreated advanced renal cell carcinoma (RCC). These results, which will be presented at the 2025 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, mark a significant milestone in the treatment paradigm, positioning the CABOMETYX-Opdivo duo as a formidable first-line therapy for a broad spectrum of patients.
Sustained Efficacy Across Multiple Parameters
The final data from the CheckMate -9ER trial demonstrate that the benefits of the CABOMETYX-Opdivo regimen endure over time. At a median follow-up of 67.6 months, the combination therapy showed:
- Progression-Free Survival (PFS): Patients on CABOMETYX plus Opdivo achieved a median PFS of 16.4 months, nearly doubling that of the sunitinib group (8.3 months) with a hazard ratio (HR) of 0.58.
- Overall Survival (OS): The median OS for patients on the combination therapy was 46.5 months, compared to 35.5 months in the sunitinib group (HR: 0.79), showcasing a significant survival advantage.
- Objective Response Rate (ORR): The ORR was markedly higher at 55.7% for CABOMETYX plus Opdivo versus 27.4% for sunitinib, underscoring the regimen’s superior tumor response.
- Durability of Response: The median duration of response (DOR) was 22.0 months compared to 15.2 months with sunitinib.
The benefits of CABOMETYX-Opdivo were particularly pronounced among intermediate- and poor-risk patients, further reinforcing its positioning as a transformative first-line therapy.
Broad Efficacy Across Metastatic Subgroups
A notable highlight from the trial is the combination therapy's effectiveness across different metastatic subgroups:
- Liver metastases: PFS increased to 10.9 months vs. 6.2 months with sunitinib (HR: 0.55), while OS improved to 37.6 months vs. 22.1 months.
- Bone metastases: PFS was 13.8 months compared to 5.3 months with sunitinib (HR: 0.43), and OS reached 34.8 months vs. 20.7 months.
- Lung metastases: PFS was 16.4 months vs. 8.3 months, with OS extending to 47.5 months vs. 32.4 months.
These findings highlight CABOMETYX-Opdivo’s ability to deliver meaningful survival improvements across a broad range of patients, irrespective of metastatic site.
Safety and Tolerability: A Manageable Profile
As with all potent oncology therapies, safety remains a critical consideration. The long-term analysis confirmed that the combination’s safety profile remains consistent with previous reports, with no new safety signals emerging. Grade 3/4 adverse events were observed in 68% of CABOMETYX-Opdivo patients, compared to 55% for sunitinib. The most common high-grade adverse events included diarrhea, hypertension, and fatigue. However, with effective dose management and supportive care, these adverse effects are deemed manageable.
Market and Competitive Landscape
A Game-Changer in the RCC Market
The RCC market is projected to see continued growth, driven by the increasing incidence of kidney cancer and the need for more effective first-line therapies. In 2025 alone, an estimated 80,980 new cases of kidney cancer will be diagnosed in the U.S., with over 21,000 patients requiring first-line systemic therapy for advanced disease.
Competitive Positioning
While sunitinib has long been a cornerstone of RCC treatment, the latest data firmly establish CABOMETYX-Opdivo as a superior alternative. However, competition remains intense with other TKI-ICI combinations such as pembrolizumab-axitinib and lenvatinib-pembrolizumab. Nevertheless, the durable benefits demonstrated by CheckMate -9ER set a new benchmark that competitors will need to match or exceed.
Key Considerations for Future Adoption
Despite the impressive clinical efficacy, widespread adoption of CABOMETYX-Opdivo faces certain challenges:
- Management of Adverse Events: The higher incidence of Grade 3/4 toxicities necessitates careful patient selection and active monitoring to ensure tolerability.
- Cost and Reimbursement: As a high-cost therapy, accessibility will depend on favorable reimbursement policies and real-world cost-effectiveness data.
- Real-World Data Validation: Further studies will be needed to confirm these findings outside the controlled trial setting and to optimize treatment sequencing strategies.
- Regulatory Considerations: While the combination is already approved in over 65 countries, continued post-marketing surveillance and potential label expansions will shape its future trajectory.
Future Outlook: Investment and Strategic Implications
The long-term success of CABOMETYX-Opdivo extends beyond clinical efficacy, carrying profound financial and strategic implications:
- Exelixis’ Financial Growth: With revenues exceeding $2.16 billion in 2024 and a strong pipeline, Exelixis is well-positioned for continued growth. The company's aggressive pipeline expansion, including novel candidates like zanzalintinib, further reinforces its market leadership.
- Patent and Exclusivity Protection: The delay of generic competition until at least 2030 enhances the commercial viability of cabozantinib, providing Exelixis with a prolonged window to maximize revenue.
- Potential for Strategic Alliances: Given the competitive oncology landscape, Exelixis may attract partnerships or acquisition interest from larger pharmaceutical players aiming to strengthen their oncology portfolios.
A New Era for Advanced RCC Treatment
The final five-year data from the CheckMate -9ER trial cement CABOMETYX plus Opdivo as a transformative first-line therapy for advanced RCC. With sustained survival benefits, broad efficacy across subgroups, and a manageable safety profile, this combination is poised to reshape treatment guidelines and patient outcomes. While challenges such as adverse event management and cost considerations remain, the long-term impact of this regimen on the RCC landscape is undeniable.
As Exelixis continues to build on this success with a strong financial foundation and a robust pipeline, the oncology market is watching closely to see how the company navigates the next phase of innovation and growth. The coming years will be pivotal, with potential new indications, regulatory approvals, and market expansions on the horizon—all of which could make CABOMETYX-Opdivo a defining force in kidney cancer treatment for years to come.