Testing the Combination of XL184 (Cabozantinib), Nivolumab, and Ipilimumab for Poorly Differentiated Neuroendocrine Tumours

Official Title

A Phase 2 Study of XL184 (Cabozantinib) in Combination With Nivolumab and Ipilimumab for the Treatment of Poorly Differentiated Neuroendocrine Carcinomas

Summary:

This phase II trial studies how well the combination of XL184 (cabozantinib), nivolumab, and ipilimumab work in treating patients with poorly differentiated neuroendocrine tumours (i.e., neuroendocrine tumour that does not look like the normal tissue it arose from). Cabozantinib may stop the growth of tumour cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumour cells to grow and spread. Giving cabozantinib, nivolumab and ipilimumab may shrink the cancer.

Trial Description

Primary Outcome:

• Overall response rate (ORR)

Secondary Outcome:

• Progression free survival (PFS)
• Incidence of adverse events
• Disease control rate (DCR)
• Duration of response (DOR)

PRIMARY OBJECTIVE:

• To evaluate the overall response rate (ORR) associated with the combination of XL184 (cabozantinib), nivolumab, and ipilimumab in patients with advanced poorly-differentiated neuroendocrine carcinomas (NECs), after the failure of at least one line of prior therapy.

SECONDARY OBJECTIVES:

• To evaluate progression-free survival (PFS).
• To measure the safety and tolerability of the combination of XL184 (cabozantinib), nivolumab, and ipilimumab in patients with advanced, poorly-differentiated NECs.
• To evaluate disease control rate (DCR).
• To measure duration of response (DOR).
• To describe the tumour molecular profile using whole exome sequencing (WES) and correlate it with treatment outcome.
• To describe the tumour molecular profile using ribonucleic acid (RNA) sequencing (RNAseq) and correlate it with treatment outcome.

EXPLORATORY OBJECTIVES:

• To measure the tumour-infiltrating CD8+ T lymphocytes in pre- and on-treatment biopsies.
• To measure tumour-infiltrating myeloid derived suppressor cells (MDSCs) in pre- and on-treatment biopsies.
• To measure tumour-infiltrating tumour-associated macrophages (TAM) in the pre and on-treatment biopsies.
• To measure the expression of programmed death-ligand 1 (PD-L1) in tumour cells and infiltrating immune cells.

OUTLINE: Patients receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-21 of cycles 1-4 and days 1-28 of subsequent cycles, nivolumab intravenously (IV) over 30 minutes on day 1, and ipilimumab IV over 90 minutes on day 1 of cycles 1-4 only. Treatment repeats every 21 for 4 cycles then every 28 days for subsequent cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4 weeks, and then every 3 months thereafter.

View this trial on ClinicalTrials.gov