CVM-1118 demonstrates 10.5-month median PFS and 77% disease control in advanced neuroendocrine tumors
Background
Neuroendocrine tumors (NETs) are a heterogeneous group of cancers that often present as highly vascularized, making them challenging to treat, especially in advanced stages. Current standard-of-care therapies, such as somatostatin analogs, everolimus, sunitinib, or PRRT, can be limited by resistance or intolerance, leaving a significant unmet need for new treatment options. This study investigates CVM-1118, a novel agent designed to disrupt vasculogenic mimicry and induce apoptosis via tumour necrosis factor receptor-associated protein 1, offering a distinct mechanism to target these refractory tumors.
Study Design
This Phase IIa trial enrolled 43 patients with grades 1-2, well-differentiated lung, gastrointestinal, or pancreatic NETs who were refractory or intolerant to one or more prior standard therapies and had progressed within 6 months. Participants received CVM-1118 (200-300 mg orally twice daily) in 28-day cycles. The primary endpoint was progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety assessments. Most efficacy-evaluable patients (N=35) had grade 2 pancreatic (63%) or gastrointestinal (34%) NETs and had undergone two prior therapies.
Results
Among the 35 efficacy-evaluable participants, CVM-1118 demonstrated promising activity. The median progression-free survival (PFS) was 10.5 months (95% CI, 5.6-22.3). The objective response rate (ORR) was 3%, while the disease control rate (DCR) was notably high at 77%. Median overall survival (OS) was not reached (95% CI, 23.8-NR), indicating sustained benefit. A sensitivity analysis in the full analysis set (N=43) showed a broadly aligned PFS estimate of 8.4 months. Patients with prior exposure to everolimus, sunitinib, or peptide receptor radionuclide therapy (PRRT) (N=22) exhibited similar findings, with a median PFS of 8.3 months. Treatment-related adverse events occurred in 44% of patients, predominantly grades 1-2, with no serious adverse events reported. This suggests a favorable safety profile.
The median progression-free survival of 10.5 months in this heavily pre-treated population highlights the potential of CVM-1118 in advanced NETs.
Key Findings
- CVM-1118 achieved a median progression-free survival (PFS) of 10.5 months (95% CI, 5.6-22.3).
- The disease control rate (DCR) was 77% in efficacy-evaluable patients.
- Median overall survival (OS) was not reached (95% CI, 23.8-NR).
- Treatment-related adverse events occurred in 44% of patients, mostly grades 1-2, with no serious events.
- Similar PFS was observed in patients with prior everolimus, sunitinib, or PRRT (8.3 months).
Why It Matters
This study introduces CVM-1118 as a promising novel oral agent for patients with advanced NETs, particularly those who have exhausted or cannot tolerate existing therapies. Its distinct mechanism targeting vasculogenic mimicry offers a new therapeutic avenue beyond traditional anti-angiogenic or mTOR-inhibitor approaches. The observed 10.5-month median PFS and 77% DCR are significant for a heavily pre-treated population, suggesting CVM-1118 could extend disease control. As an oral medication, it also offers convenience and potentially improved quality of life compared to intravenous options. Further research is warranted to integrate this agent into existing treatment algorithms and explore combination strategies.
cvm-1118
neuroendocrine-tumors
net
phase-2a-trial
cancer
vasculogenic-mimicry