Cabometyx (cabozantinib tablet)

P2, N=20, Recruiting, University Health Network, Toronto | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Aug 2025 --> Jun 2026

P2, N=29, Recruiting, University of Arizona | Trial completion date: Oct 2025 --> Jan 2026 | Trial primary completion date: Oct 2025 --> Jan 2026

Radiopharmaceuticals such as 131I-MIBG and 177Lu-DOTATATE continue to play a pivotal role, achieving disease control in many patients. Cytotoxic regimens, particularly temozolomide, remain relevant, with some studies suggesting that SDHB-mutated PPGLs demonstrate a heightened sensitivity associated with MGMT promoter hypermethylation and reduced MGMT expression. Targeted agents are increasingly important: multi-kinase inhibitors such as sunitinib, anlotinib, and cabozantinib have shown meaningful activity. The landmark approval of belzutifan, a HIF-2α inhibitor, in 2025 represents the first oral targeted therapy for advanced/metastatic PPGL, which is particularly relevant for pseudohypoxic Cluster 1 tumors...This review summarizes current evidence and highlights ongoing clinical trials, underscoring a paradigm shift toward precision medicine and rational combination strategies. Collectively, these advances bring cautious optimism that metastatic PPGLs may soon become a more manageable chronic disease with improved survival and quality of life.

In treatment, radioligand therapy (PRRT) is used earlier in appropriate receptor-positive disease; cabozantinib improves progression-free survival after prior therapy; and belzutifan offers a biomarker-guided option for malignant pheochromocytoma/paraganglioma...We appraise strengths and limitations of key trials, note issues of access and toxicity, and highlight active areas in development (SSTR antagonists, alpha emitters, and dose-guided PRRT). Our goal is to provide a concise, evidence-based map of the field to support informed clinical judgment and future research priorities.

Immune checkpoint inhibitors (tremelimumab and durvalumab) in combination with small- molecule agents (lenvatinib and cabozantinib) enhance T-cell activation and improve progression-free survival in HCC...HCC ME has distinct immune subtypes exhibiting different responses to treatments, which complicates biomarker selection and treatment timing. Personalized therapy based on ME is the future path in HCC management.

P2, N=35, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting | Trial completion date: Mar 2027 --> Sep 2026 | Trial primary completion date: Jul 2026 --> Mar 2026

Subsequently, the patient started gefitinib treatment, and 3 months later, the treatment effect assessment showed a partial response (PR) at regular follow-up according to RECIST evaluation criteria...Two months later, imaging examination showed that the lesions in various parts of the body were stable. Except for dryness of oral and nasal mucosa, the patient did not experience other serious adverse reactions.

Cabozantinib and nivolumab was associated with limited response in patients with epNET. Alternative strategies to enhance the immune response in epNET are needed.

Herein, we report a series of compounds featuring a novel piperazine-amide scaffold, designed and synthesized from BLU-667 via sequential bioisosteric replacement, linkage truncation, and subsequent structure-activity relationship (SAR) optimization...Furthermore, it exhibited favorable oral pharmacokinetic properties in mice, demonstrating superior in vivo efficacy compared to the multikinase inhibitor cabozantinib. In conclusion, compound 13 is a promising preclinical candidate.

P1, N=18, Completed, Washington University School of Medicine | Active, not recruiting --> Completed

P3, N=904, Not yet recruiting, Merck Sharp & Dohme LLC

A reanalysis of previous clinical trial data revealed lower efficacy of sunitinib in patients with KDM6A-low ccRCC. Consistently, KDM6A-deficient cells showed resistance to cabozantinib and decreased expression of target molecules of TKIs. KDM6A deficiency contributes to ccRCC progression and TKI resistance, suggesting that targeting KDM6A-related pathways may offer new therapeutic strategies for patients with KDM6A-deficient ccRCC.