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Melanotan-2

MT-II, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2

Quick Stats
Studies 3
Trials 100
Recruiting PHASE2 INTERVENTIONAL NCT05904080

Testing Nivolumab and Ipilimumab Immunotherapy With or Without the Targeted Drug Cabozantinib in Recurrent, Metastatic, or Incurable Nasopharyngeal Cancer

View on ClinicalTrials.gov Updated Dec 15, 2025

Brief Summary

This phase II trial tests how well nivolumab and ipilimumab immunotherapy with or without cabozantinib works in treating patients with nasopharyngeal cancer that has come back (after a period of improvement) (recurrent), has spread from where it first started (primary site) to other places in the body (metastatic), or for which no treatment is currently available (incurable). 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 tumor cells to grow and spread. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving immunotherapy with nivolumab and ipilimumab and targeted therapy with cabozantinib may help shrink and stabilize nasopharyngeal cancer.

Detailed Description

PRIMARY OBJECTIVE: I. To determine if the progression-free survival (PFS) of the triplet combination (cabozantinib S-malate, nivolumab, and ipilimumab \[CaboNivoIpi\]) is more favorable than the doublet (nivolumab and ipilimumab \[NivoIpi\]). SECONDARY OBJECTIVES: I. To compare safety and tolerability between the two arms (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5.0.). II. To compare overall response rate (ORR) between the two arms via both Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST) criteria. III. To compare overall survival (OS) between the two arms. IV. To assess response by primary or acquired PD-1/L1 inhibitor resistance in the prior line of therapy. EXPLORATORY OBJECTIVE: I. To evaluate molecular and immunologic predictors of response (Epstein-Barr virus \[EBV\] viral load; PD-L1 score) between arms. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and collection of blood samples throughout the trial. ARM B: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 and cabozantinib S-malate orally (PO) daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may continue with cabozantinib S-malate after 2 years per treating investigator. Patients undergo CT or MRI and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up every 8-12 weeks until progression of disease occurs or a new non-protocol anti-cancer therapy is initiated and then every 6 months for up to 2 years.

Interventions

Name: Biospecimen Collection
Type: PROCEDURE
Description: Undergo collection of blood samples
Name: Cabozantinib S-malate
Type: DRUG
Description: Given PO
Name: Computed Tomography
Type: PROCEDURE
Description: Undergo CT scan
Name: Ipilimumab
Type: BIOLOGICAL
Description: Given IV
Name: Magnetic Resonance Imaging
Type: PROCEDURE
Description: Undergo MRI
Name: Nivolumab
Type: BIOLOGICAL
Description: Given IV

Primary Outcomes

Measure: Progression-free survival (PFS)
TimeFrame: From randomization to the first of either progression or death from any cause, or censored at last known tumor assessment date, assessed up to 2 years
Description: PFS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.

Trial Information

NCT ID

NCT05904080

Status

Recruiting

Study Type

INTERVENTIONAL

Phases

PHASE2

Sponsor

National Cancer Institute (NCI)

Last Updated

December 15, 2025