Reversing Resistance in Melanoma

Antoni Ribas, MD, PhD

Professor, Medicine, Surgery and Molecular and MedicalView Bio

Ribas is an associate professor with a double appointment in medicine (hematology-oncology) and surgery (surgical oncology) at the University of California, Los Angeles (UCLA). He is also an assistant director for clinical programs at the UCLA Human Gene Medicine Program, director of the JCCC Cell and Gene Therapy Core Facility, General Clinical Research Center Advisory Board Member and faculty advisor to the UCLA Residency Program.

Ribas trained at the University of Barcelona in Spain, and has undergone postdoctoral training at the Sidney Kimmel Cancer Center in San Diego and at UCLA. He joined the UCLA Hematology-Oncology Fellowship program and has been a faculty member since July of 2001.

Ribas and his colleagues are conducting studies aimed at understanding how the immune system can be effectively used to treat cancer. The work is focused on the ability to activate killer immune cells specifically targeted to the cancer. One line of research is the use of dendritic cells engineered to express tumor antigens, which have been shown to induce powerful responses against cancer. This approach has been taken from preclinical studies in mice to a phase I clinical trial for the treatment of patients with malignant melanoma. Assays with defined performance specifications determined in detailed methodology studies are being used for the immune monitoring of the human clinical trials. Another line of research is the stimulation of innate responses to tumors. Dendritic cells are very powerful in activating natural killer cells that lead to tumor regressions, and the immunobiology of these responses are being studied. Additional interests of the laboratory are the use of interventions that modify the regulation of tumor-specific lymphocytes, and the pharmacological modulation of the interaction between the lytic immune cells (cytotoxic T lymphocytes or natural killer cells) with the cancer cells, with the goal of further increasing their antitumor potential.

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Meet the Team

  • Antoni Ribas, MD, PhD, University of California, Los Angeles
  • Siwen Hu-Lieskovan, MD, PhD, University of California, Los Angeles
  • Ari VanderWalde, MBioeth, MPH, MD, University of Tennessee College of Medicine
  • Michael Wu, PhD, Fred Hutchinson Cancer Research Center
  • Jeffrey Sosman, MD, Northwestern University
  • Kenneth Grossmann, MD, PhD, University of Utah
  • Alain Algazi, MD, University of California, San Francisco
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About this SU2C Catalyst Clinical Trial

Do you have metastatic melanoma? Has your cancer progressed after you have been on anti-PD-1/L1 therapy? Stand Up To Cancer (SU2C) is supporting a clinical trial that is studying a potential new immunotherapy treatment for patients like you.

Researchers at the National Cancer Institute (NCI) believe that some tumors may have developed a way to evade the anti-PD-1/L1 therapy by blocking immune cells from attacking the tumor. This study will test the theory that adding an additional treatment, ipimumab, will make the cancer cells respond once again to the anti-PD-1/L1 therapy.

The trial will be conducted by the NCI through SWOG, a network of cancer clinical trial researchers. The trial will be offered at 47 locations throughout the U.S., including national cancer centers, community hospitals, private practices and physician group networks.

We Need You

Why your Participation Matters

Your participation in this study could help researchers find out why immunotherapy treatments sometimes stop working. That could lead to better treatments, and improve outcomes for cancer patients in the future.

Here’s a little more about how anti-PD-1/L1 therapy works, to help explain: PD-1 is called a checkpoint protein. It is found on the surface of a type of immune cell. PD-L1 is a related protein found on the surface of some normal cells in the body. The two proteins can attach to one another like a lock and key. When they do, it sends a signal to the immune cells, telling them, “Don’t destroy this cell. It’s normal.” Some cancer cells have a lot of PD-L1. That helps them avoid destruction by the body’s immune system.

Drugs that inhibit PD-1 or PD-L1 can block this binding process, allowing the immune system to respond to the cancer cells; however, many of these drugs only work for a short time.


Key Insights for Participants

What is Ipilimumab?

A monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

What is Nivolumab?

A fully human immunoglobulin G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (“PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities.

Because clinical trials must be carefully tracked, you may receive more attentive care. For example, you will have more access to doctors and nurses to answer questions, get more tests and be closely monitored.

The purpose of this study is to test any good and bad effects of the combination of ipilimumab and involumab. While the combination treatment could help the immune system to react to melanoma, reducing the number of cancer cells, it could also cause side effects.

Both ipilimumab and nivolumab have been FDA-approved to treat advanced melanoma, but there has been no FDA approval for using them in this way, to treat melanoma that has previously gotten worse after treatment with an anti-PD-1/L1 drug.

You will be assigned randomly to one of two treatment groups in the study: treatment with a combination of therapies, or treatment with a single drug. You will not be given a placebo (“sugar pill”). You will receive the study drugs as long as your cancer doesn’t get worse, the side effects are tolerable, and you agree to stay in the study.

You will not have to pay for the drugs while you are in the study, but will be responsible for all the other costs of treating your cancer, including the cost of getting the medicine ready and giving it to you, the cost of tests, procedures, and any medicines to manage your side effects.


Patients with metastatic melanoma, either Stage IV or unresectable Stage III, progressing on prior anti-PD-1/anti-PD-L1 therapy (ex. nivolumab, pembrolizumab).

Key criteria are summarized below and can be found in detail on Interested patients will need to review their medical histories with clinical trial patient coordinators before they can be accepted to participate in this trial.

Male or Female
Age Range:
18 years and older
Patients with metastatic melanoma whose disease is progressing


You are NOT eligible if your doctors think your melanoma can be surgically removed.

You are NOT eligible if, while you were taking the anti-PD-1/L1 agent, your tumors overall shrank by more than 30% before getting worse again.

If the cancer has spread to your central nervous system (CNS), those tumors must be treated with stereotactic radiation therapy, craniotomy, Gamma Knife® therapy,

or whole brain radiotherapy, and afterward there must be no evidence that the disease progressed in your CNS.

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You are NOT eligible if you were previously treated with ipilimumab or other CTLA-4 antagonists. You are also NOT eligible if you have had systemic therapy between

the time your disease progressed (while on the anti-PD-1/L1 agent) and your registration for the trial. Systemic therapy before your anti-PD-1/L1 therapy is allowed. You also must not be planning to have any other form of systemic anti-tumor treatment during the course of this trial.

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You must stop taking your anti-PD-1/L1 therapy at least 21 days before you register for this trial.

You can NOT have taken steroids or any other immunosuppressor for at least 14 days before you register for the trial. Inhaled or topical steroids, and adrenal

replacement medications (less than 10mg/day of prednisone, for example) are acceptable, as long as you don’t have an active autoimmune disease that would require treatment with steroids during the trial.

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If you had HIV in the past, you must have a normal CD4 count 28 days before you register for the trial.

Before beginning the trial you must be well enough to be out of bed more than half the time during waking hours, and able to care for yourself. This is determined by

scoring 2 or less on what’s called the ECOG, or Zubrod, Performance Status Test.

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You are NOT eligible to participate in this study if you have had a different type of malignant cancer unless you have been disease-free for two years or are in

complete remission.
Note: You MAY participate if you have been treated for basal cell or squamous cell skin cancer or cervical cancer that was “in-situ” (had not spread).

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You are NOT eligible to participate if you have active hepatitis B or hepatitis C infection, any active infection that requires systemic therapy at the time of

registration, or have organ allografts.

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You are NOT eligible to participate in this clinical trial if you are pregnant, expecting to conceive a child either during this study or within four months

following your last treatment in this study, or are breast feeding. If you are physically able to become pregnant, you must have a negative pregnancy test (a blood test ordered by your doctor) within the 48-hour period before you start treatment under this study. If you are fertile (both men and women) you must agree to use an effective birth control method from the time of enrollment until 31 weeks after receiving the last treatment dose in this study.

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You play a vital role.

Here are the locations where you can participate in this clinical trial. If you are interested, please contact the patient coordinator at your preferred site. The patient coordinator is there to help you understand every aspect of the clinical trial process and can answer any questions you may have.

The patient coordinator will start by reviewing your medical history with you to see whether you meet all the criteria to participate. The coordinator will then guide you through a detailed “informed consent” document that you are required to review and sign when you enroll in a clinical trial.

The trials are conducted by National Cancer Institute (NCI) through the Southwestern Oncology Group (SWOG) network. Investigators in the SWOG network who are registered members of the SWOG Cooperative Group can enroll patients. Currently, there are 186 sites conducting trials across the country. For more information on SWOG study sites, please visit the SWOG website at

SWOG | Leading Cancer Research. Together.

Danae Campos
Operations Office
Protocol Coordinator
4201 Medical Drive #250 | San Antonio TX 78229
Ph: 210.614.8808, ext 1022 | Fax: 210.614.0006


For more information about this and other trials, click on the link below.
Visit SWOG at +

Find out if there's a trial for you. Reach out today.

Even if you do not meet the requirements for this trial, there may be other trials for you. Get started with the SU2C Clinical Trial Finder, a free and confidential cancer clinical trial matching and referral service.

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