Studies will evaluate combination therapies for two types of melanoma

Melanoma has the distinction of being a rare form of skin cancer, but one that causes most skin cancer deaths in the United States. Only 1 percent of skin cancers fall under melanoma, which develops when melanocytes grow out of control. Melanocytes are cells in the skin that produce dark pigment, also known as melanin. The American Cancer Society estimates that nearly 100,000 new cases will be diagnosed and approximately 7,700 people may die from melanoma in 2022. 

There are multiple stages of melanoma skin cancer, ranging from stage 0 (melanoma is in one place), through stage IV. At stage IV, the cancer has spread (metastasized) into lymph nodes, to skin in other parts of the body, or to the lungs, liver, brain or bones. While some advanced melanoma cancers respond to treatment, other forms do not respond and continue to progress.  

A new investigator-initiated clinical trial sponsored by Earle A. Chiles Research Institute, a division of Providence Cancer Institute of Oregon, will evaluate the efficacy of a new triple combination therapy (ipilimumab, nivolumab and cabozantinib) for patients with metastatic melanoma that is unresponsive to standard immunotherapy.  

Triple combination therapy  

Ipilimumab and nivolumab are immunotherapies that boost the immune system by blocking proteins that de-activate the immune system (immune checkpoints). Ipilimumab was the first immune checkpoint inhibitor to receive FDA approval as a cancer therapy. People being treated for advanced metastatic melanoma using ipilimumab had better overall survival rates. Subsequent clinical trials with ipilimumab alone and in combination with nivolumab have shown a clinical benefit in patients with melanoma, renal cell carcinoma, non-small cell lung cancer and other cancers. 

Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking abnormal proteins that signal cancer cells to multiply and spread. Blocking these proteins helps kill cancer cells and slow the spread of tumors. Cabozantinib has been approved to treat thyroid cancer, kidney and liver cancers, but is still considered experimental for treating melanoma.  

Recent clinical trials have shown that the combination of kinase inhibitors with immunotherapy can be very effective for treating advanced cancers, such as endometrial and kidney cancers. This new clinical trial will determine if the triple combination of cabozantinib plus ipilimumab and nivolumab will result in improved treatment of advanced melanoma. 

Eligible participants 

This phase II, clinical trial is open to eligible adults with a confirmed diagnosis of metastatic cutaneous melanoma. The triple combination therapy will be given over 24 months or until either the melanoma grows or spreads, or the study participant experiences an unacceptable drug-related toxicity.  

Matthew Taylor, M.D., co-medical director, Providence Melanoma Program, and medical director, Providence Thyroid Cancer Program, is the principal investigator of the study. Providence is the only location in the world currently recruiting patients.  

Learn more about the study here: 

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

New study starts recruiting patients with metastatic uveal melanoma in June  

A new clinical trial will evaluate the efficacy of two medications in patients with metastatic uveal melanoma. The investigator-initiated study is sponsored by Earle A. Chiles Research Institute. The principal investigator is Matthew Taylor, M.D., co-medical director, Providence Melanoma Program, and medical director, Providence Thyroid Cancer Program. 

This phase II study will be open to adults with metastatic uveal melanoma (eye cancer) who have not received immune checkpoint inhibitor therapy.  

Uveal melanoma is a rare type of melanoma that starts in the eye. Metastatic uveal melanoma means the cancer has spread from the eye to other parts of the body.  

Two medications used in the study 

Pembrolizumab is one of two medications being administered in this study. Our researchers participated in clinical trials leading to FDA approval of pembrolizumab as a treatment for melanoma in 2014. An immunotherapy and immune checkpoint inhibitor, pembrolizumab is now used to treat many different types of cancer. By binding to the protein PD-1, pembrolizumab helps immune cells kill cancer cells.  

Lenvatinib, the second medication used in this study, is a kinase inhibitor used to treat various types of cancer. Kinases are proteins that help control functions, such as metabolism and cell growth. Kinases can be more active in cancer cells, contributing to rapid growth. Using a kinase inhibitor, such as lenvatinib, may block kinase activity in cancer cells, thereby stopping or slowing the growth of cancer. Lenvatinib is considered experimental in treating melanoma. 

Dr. Taylor led the initial clinical trial that tested the combination of lenvatinib plus pembrolizumab in patients with advanced cancer. The clinical trial showed this combination was very effective for patients with metastatic endometrial and kidney cancers. The combination therapy has been approved for use in the U.S. and Europe to treat advanced endometrial and kidney cancers. 

Eligible participants in the metastatic uveal melanoma study will be treated with the combination of lenvatinib and pembrolizumab every three weeks for a maximum of two years. 

This trial is currently recruiting patients. Providence is the only location in the world offering this clinical trial to patients with advanced uveal melanoma. 

Learn more about the study here: 

Lenvatinib Plus Pembrolizumab In Patients With Immune Checkpoint Inhibitor Naïve Metastatic Uveal Melanoma 

Melanoma studies: can adjuvant immunotherapy improve recurrence-free survival? 
Melanoma study: Are two therapies better than one? 
Cancer Moonshot relaunch aligns with Providence initiatives to reduce cancer burden and improve health equity