Study of Ipilimumab, Nivolumab, and Cabozantinib in Patients With Cutaneous Melanoma

Conditions

• Refractory Cutaneous Melanoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Ipilimumab — DRUG
  Ipilimumab is a fully human IgG1 kappa monoclonal antibody that binds the co-inhibitory receptor CTLA-4. Antibody binding prevents interaction with the CTLA-4 ligands CD80 and CD86. Blockade of CTLA-4 results in increased T cell activation and proliferation. Ipilimumab was the first immune checkpoint inhibitor to receive FDA approval as a cancer therapy. Treatment of patients with advanced metastatic melanoma with ipilimumab monotherapy resulted in improved overall survival. Subsequent clinical trials with ipilimumab alone and in combination with anti-PD-1 antibodies have demonstrated impressive clinical activity in patients with melanoma, renal cell carcinoma, non-small cell lung cancer and other cancers. Side effects of ipilimumab result from autoimmune attack on healthy tissues. Side effects may include dermatitis, colitis, hepatitis, hypophysitis, pneumonitis, endocrinopathies, nephritis, arthritis, neuropathies and others.
• Nivolumab — DRUG
  Nivolumab is a fully human IgG4 kappa monoclonal antibody that binds the co-inhibitory receptor PD-1. Nivolumab binding to PD-1 blocks interaction with the PD-1 ligands PD-L1 and PD-L2. PD-1 blockade can lead to reinvigoration of exhausted T cells and prevent T cell exhaustion of newly activated T cells. Nivolumab has been shown to have excellent clinical efficacy in treating a wide range of cancers as monotherapy and in combination with ipilimumab.
• Cabozantinib — DRUG
  Cabozantinib is a potent small molecule inhibitor of multiple receptor tyrosine kinases. Cabozantinib inhibits VEGFR2, MER, KIT, and MET at single digit nanomolar IC50 concentrations. Other kinases including ROS1, RET, FLT3, RON, AXL, and TIE2 are also inhibited with nanomolar concentrations of cabozantinib. Cabozantinib has been shown to have clinical activity in a variety of solid tumors and has been approved by the FDA for treatment of medullary thyroid cancer, renal cell carcinoma and hepatocellular carcinoma.

Study Details

The primary objective of this clinical trial is to evaluate the clinical efficacy and progression free survival of the triplet combination of ipilimumab + nivolumab + cabozantinib in patients with anti-PD-1/PD-L1 refractory metastatic cutaneous melanoma.

Key Dates

Start date

Jun 8, 2022

Status verified

Aug 2024

Primary completion

Sep 11, 2023

Completion

Jul 23, 2024

Study Design

Enrollment

4 participants (actual)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Cabozantinib + Ipilimumab + Nivolumab
  Ipilimumab 1 mg/kg + Nivolumab 3 mg/kg IV every 3 weeks + Cabozantinib 40 mg PO daily for 4 cycles followed by Nivolumab 480 mg IV every 4 weeks + Cabozantinib 40 mg PO daily for up to 24 months.

Primary Outcome Measure

Progression Free Survival of the Triplet Combination of Ipilimumab + Nivolumab + Cabozantinib in Patients With Anti-PD-1/PD-L1 Refractory Metastatic Cutaneous Melanoma [ Time Frame: 7 Months ]

Locations (1)

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