Cabometyx (cabozantinib tablet)

Within the limitations of a single-arm phase II trial, cabozantinib demonstrates both safety and antitumor activity in mCRC. The observed correlation between specific molecular features, such as EMT activation and angiogenesis, and cabozantinib activity is hypothesis-generating and warrants further investigation.

However, the metastatic RCC progressed after another 3 months, and the patient received two lines of tyrosine kinase inhibitors (sunitinib and cabozantinib)...Severe cerebral vasculitis requires hospitalization with prompt diagnostic workup and immunosuppressive treatment. Despite the preterm permanent discontinuation of immunotherapy, the patients can benefit from the systemic treatment.

P2, N=100, Recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Apr 2029 | Trial primary completion date: Apr 2026 --> Apr 2029

Molecular profiling leveraged IMmotion151 (A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma) trial data with whole-exome sequencing, RNA sequencing, and programmed cell death ligand 1 immunohistochemistry. Systemic standard of care treatments for mRCC, which include vascular endothelial growth factor receptor targeted therapy (VEGF-TT [sunitinib or pazopanib]), immune-oncology-VEGF (IO-VE [pembrolizumab and axitinib, pembrolizumab and lenvatinib, nivolumab and cabozantinib, or avelumab and axitinib]), and 2 IO (IO-IO [ipilimumab and nivolumab]) regimens...In this cohort study, the very favorable risk subgroup had a less immunogenic molecular profile and superior outcomes from VEGF-containing regimens (VEGF-TT and IO-VE) compared with the favorable risk group. The IO-IO combination showed significantly worse survival in this population, suggesting that VEGF inhibition remains essential for optimal outcomes.

P=N/A, N=100, Completed, Istituto Oncologico Veneto IRCCS | Active, not recruiting --> Completed

Early multi-kinase inhibitors such as vandetanib and cabozantinib demonstrated modest efficacy with significant toxicity, whereas the selective RET inhibitors selpercatinib and pralsetinib have achieved improved response rates and tolerability...Nonetheless, resistance, driven by secondary mutations and bypass signaling, presents a major therapeutic challenge. Ongoing development of next-generation inhibitors and combination strategies aims to overcome resistance and improve patient outcomes.

P1, N=6, Active, not recruiting, Providence Health & Services | Trial completion date: Dec 2026 --> Dec 2029 | Trial primary completion date: Dec 2025 --> Dec 2027

Cabozantinib, a multikinase TKI targeting VEGFR, MET, and AXL, represents one of the most established treatment options in this context. This mini-review summarizes the biological rationale, key clinical evidence, and the most recent data presented at major international congresses, with a specific focus on the positioning of cabozantinib after failure of immunotherapy-based regimens or immune-TKI combinations.

The proportion of the patients benefitting of the treatment and its safety profile justify larger, controlled studies to further investigate the added role of combining cabozantinib with metronomic temozolomide. ClinicalTrials.gov identifier: NCT04893785.

P1/2, N=49, Recruiting, National Health Research Institutes, Taiwan | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Aug 2026 --> Aug 2027

P2, N=20, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2027 --> Dec 2027 | Trial primary completion date: Jan 2027 --> Dec 2027

P1, N=300, Recruiting, Kura Oncology, Inc. | N=66 --> 300