MSK Plays Critical Role in FDA Approval of New Melanoma Drug

By Jim Stallard,

Tuesday, January 6, 2015

Sandra D’Angelo and Jedd Wolchok

A new treatment for advanced melanoma is the latest promising advance in immunotherapy tested in large part by our scientists.

On December 22, the US Food and Drug Administration approved a new treatment for people with melanoma that cannot be surgically removed or has metastasized, or spread, and no longer responds to other therapies. After the drug, nivolumab (Opdivo), was shown to shrink tumors in a clinical trial, it received accelerated approval, which allows patients earlier access to promising therapies that show effectiveness during a study.

Memorial Sloan Kettering physicians helped spearhead clinical trials testing nivolumab’s safety and effectiveness and continue to conduct studies using the drug to treat melanoma and other cancers. In particular, MSK was one of the primary sites for the multi-center phase III trial that directly led to the FDA approval, enrolling a large number of patients in the study.

Nivolumab inhibits the PD-1 protein, a molecule on the surface of immune cells that acts as a brake to prevent the immune system from attacking tumors. Blocking PD-1 takes the brakes off and allows the immune cells to destroy the cancer.

A Striking Result

Metastatic melanoma is the deadliest form of skin cancer, and until recently treatment options had been very limited for those whose cancer progressed after initial treatment. In the phase III trial, nivolumab shrank tumors in 32 percent of patients — an effect that lasted for more than six months in approximately one-third of those who experienced the reduction.

“This type of dramatic benefit is not typically seen in cancer patients. These are patients who did not respond to other standard therapies, so these drugs are really practice-changing,” says medical oncologist Sandra D’Angelo, who led the MSK portion of the trial along with medical oncologist and immunologist Jedd Wolchok.

The FDA approved nivolumab for patients whose melanoma has progressed after previously being treated with ipilimumab (Yervoy™) — another drug that harnesses the immune system — and also for patients whose tumors express a gene mutation called BRAF V600 and who have already received ipilimumab and a BRAF inhibitor.

Dr. Wolchok and MSK medical oncologist Michael Postow are now leading clinical studies testing nivolumab as an initial frontline therapy in melanoma patients.

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Immunotherapy: The New Paradigm

Nivolumab is the latest in a new generation of cancer therapies that unleash the immune system to destroy cancer cells. This approach, which MSK physician-scientists played a major role in developing, is producing stunning results when combined with standard anticancer therapies.

The first such immunotherapy drug, ipilimumab, was approved in 2011 and acts on a different immune cell protein called CTLA-4 to achieve a similar effect.  Much of the basic research identifying CTLA-4 as a critical target was done by immunologist James Allison, who spent nearly a decade of his career at MSK before leaving in 2012 for MD Anderson Cancer Center in Houston. Ipilimumab has already produced impressive results in some melanoma patients, dramatically extending life expectancy.

In September 2014, another drug, pembrolizumab (Keytruda™), became the first anti-PD-1 therapy to be approved by the FDA, also for the treatment of advanced melanoma. Dr. Wolchok helped guide both ipilimumab and pembrolizumab through late-stage clinical trials.

“Our approach to melanoma has really been transformed over the last three years, beginning with the approval of ipilimumab,” Dr. D’Angelo says. “Patients are now living with a disease for which there had been no effective options. It’s a testament to our involvement and commitment to immunotherapy and Dr. Wolchok’s ability to make this happen here at our institution.”

The impact of nivolumab and similar immunotherapy drugs extends well beyond melanoma. Dr. D’Angelo says her main interest now lies in using immunotherapy to treat sarcoma, a type of cancer which, like melanoma, also has had limited treatment options. She will be leading a phase II clinical trial opening in the spring of 2015 testing nivolumab alone or in combination with ipilimumab in sarcoma patients. The national study will be conducted through the Alliance for Clinical Trials in Oncology, a network sponsored by the National Cancer Institute.

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I am so glad there will be an anti-PD1 and anti-CTLA4 combo trial for sarcoma patients! Thank you MSKCC!

I am a sarcoma patient in Burlington, Vermont. My oncologist at University of Vermont Medical Center has applied for this trial. Please advocate for us to be included. I need this treatment!

Vermonter, the good news is, now that this drug has been approved by the FDA you no longer need to be part of a trial to have access to it. We recommend you speak to your oncologist about it. Thank you for your comment.

I think there is a misunderstanding. Are you saying these drugs are available for use in treating sarcoma? Your article states in the last paragraph that a study will begin this spring for sarcoma. That's what I am asking about, not melanoma.

Vermonter, sorry we misunderstood your question! We're going to send a message with more information on the sarcoma trial to the email address that you provided.

I am HALFWAY THROUGH MY IPI TREATMENT under the guidance of my oncologist,Dr Magi Khalill who has links to MSK so articles like these fo wonders for my faith in the plan we have worked out for my braf metastatic melanoma as I totally understand what and better yet why the path we are going down. Thanks for the education.

As a synovial sarcoma patient from Denmark I welcome the forthcoming combination trial of nivolumab and ipilimumab in sarcoma. I’m sure we are many sarcoma patients around the world who have high hopes that you will be able to replicate the impressing results from the equivalent melanoma trials. Good luck. Will the trial be open for non-US citizens?

Dear Henrik, you may reach out to our International Center and inquire about your eligibility for that trial. Their email is or to learn more you can visit their page at

There would also be more information available on, where trials from all over the world are listed.

We hope this is helpful. Thank you for your comment.

My 31 yr old daughter lost her battle with melanoma in 2009. We never did determine the mole or pointy of entry of the melanoma. She had just given birth and I beleive a high estrogen level can trigger the disease. Are ther any warning signals other than visual body scans? The team at Memorial was so supportive and the nurses and staff were professional and caring

Could you'll tell me if there is any data on use of these drugs in Ovarian setting for platinum and multi drug resistance. Even clinical or laboratory data?

Dear Sudhir, a good way to keep track of clinical trial results for ovarian cancer is through the National Cancer Institute. Here is a link to the latest practice-changing data on ovarian cancer treatment: ovarian&page=1&RecordsPerPage=5&Offset=0

Also, posts results to all completed studies. Here's a link to a search for ovarian cancer study results that you may browse:…

Our researchers are currently studying a drug combination for patients with platinum-resistant ovarian cancer. The description for this trial (along with a listing of our other trials for ovarian cancer) can be found here:

We hope this is helpful. Thank you for reaching out to us.

I have melanoma in my lungs, diagnosed in August of last year. I also have Crohn's Disease, I have been to Johns Hopkins and Duke, all of the doctors warn, do not take Yervoy. Since I cannot take Yervoy, i don't qualify for Nivolumab. Temador did not help. I am 78 years old. Do you have any suggestions? Thanks Ron Cole

Ron, thank you for reaching out. We are sorry to hear about your diagnosis.
If you want to make an appointment with one of our specialists for a consultation and discussion of what treatment options may be appropriate for you, we suggest you call our Physician Referral Service at 800-525-2225 or go to Thanks for your comment.

With these two new drugs out after using Mekinist and Tafinlar with no results what would be the next step? Opdivo, Keytruda or the older Yervoy?

Keith, we are not able to provide advice about medication on our blog. If you'd like to speak to a doctor at MSK, you can call 800-525-2225 or go to for more information on making an appointment. Thank you for your comment.

My husband is a current patient of Dr. Tap at MSKCC he wants to get into this trial what can he do to get on the list.

Selina, you and your husband should speak to Dr. Tap about this. He should be able to tell you whether the trial is right for your husband. Thank you for your comment.

I've got a choroidal melanoma in my left eye. I got it checked (at Sloan Kettering) and it hasn't grown, but has left me with seemingly permanently blurred vision in that eye. Is there any chance this may help reduce the melanoma in my eye and clear up my vision?

Oliver, thank you for your comment. We recommend that you discuss your particular case and possible treatment with nivolumab with your doctor (either the MSK physician you saw or your personal physician).

My husband has metastic salivary gland cancer that shrunk under chemo and appears to be recurring. He is in consultation with a doctor in our state and may be eligible for a clinical trial to try immunology that has worked for melanoma. We plan to be in NYC beginning 2/20 and hope to make a consultation for another opinion and more information as this is new material for us. Due to the date and time this is our first time to connect to SK. If you have any targeted information I would appreciate it as I continue to explore your website and attempt to make an appointment.

Jean, we're sorry to hear about your husband's diagnosis. You can call 800-525-2225 or go to for more information on making an appointment. Our doctors will be able to discuss treatment options with you, including what kinds of clinical trials may be available. Thank you for your comment.

I currently am dealing with Stage IV Metastic Melanoma. I find out in April the results of my latest series of scans. If I'm in remission Great if not then I'll just take the next step. I look at it as a baseball game. Some Innings I'll win and some Innings I'll lose. I'm going to win this game. I a firm be-leaver in what I call PMA, Positive Mental Attitude,I don't beleave in Bad Days and I call the pain scale you see in Dr's offices the Retard Scale. I use levels of discomfort and tell the Doctor I need to convert his chart to my way of thinking. I may start out with the bad day but by breakfast I got myself under control. I was on Yervoy and only had one half way uncomfortable day. The only major side effect was my Pituitary gland I was told about before treatment started.So now I take a few extra pills and a Testosterone shot once a week. No big deal. If the Yervoy didn't work as I told by wife No big deal we will try something else. I plan to live until I'm 100 and that means 32 years to go. If I'm not in remission then I'll talk to my oncologist about this new drug and see what he says. I go to West Michigan Cancer Center in Kalamazoo,Michigan. Remember to stay on the upside of things.I woke up one morning and saw the Well Diggers Butt and swore I'll never see it again until my 100th birthday.

My melanoma started in my right eye. Had radiation plaque therapy @ Cleveland Clinic. My latest scans show it has metasticized to my liver. Have just completed seconded Yervoy treatment. Unable to get into clinical trials due to left kidney removal--carcinoma. Is there anything more I can do if Yervoy dose not work. Please help me. I am 78 years old. Thank You

Yvonne, we are sorry to learn about the metastasis. If you would like to have a consultation with a Memorial Sloan Kettering physician regarding treatment options, please call our Physician Referral Service at 800-525-2225 or go to Thanks for your comment.

My wife who is 45 yo recently had a brain tumor removed (dec 31 2014) and also has a small lesion on her lung. She has been diagnosed with stage IV metastatic melanoma and is currently receiving yervoy and will subsequently start a Braf inhibitor. I've been reading some case studies concerning this type of regiment and even with this type of immunotherapy, the prognosis (16 mos) isn't very reassuring. I've read that some pt's are living 10+ years after treatment. What are some of the cofactors that may be involved in this type of prognosis? Thank you for your time. DT

Dominic, we are sorry to hear about your wife. The question about why these melanoma drugs work better on some people than others is something that researchers are actively investigating here at MSK. You can read about a recent study in this area here:… There are still a lot of things that are unknown, but we are making progress. Thank you for your comment.

I am a patient at MSK. Can these drugs work on rectal cancer mestasized to the lungs. I am told there is nothing left for me.

Hi, Brenda, we are sorry to hear about your diagnosis. We have a number of trials that are evaluating immune therapies for people with colorectal cancer:…
You may be interested in talking with your physician about whether considering a clinical trial might be appropriate for you. He or she can tell you whether you meet the eligibility criteria necessary to participate. Thank you for reaching out to us.

My doctor, Victor Villalobos, at University of Colorado, in Denver, mentioned a soft tissue sarcoma trial to be conducted by The Alliance (?) soon. do you know about this and how do i find information about it? this was first noticed on a PET scan in April/May 2013 and began treatment in Jan 2014. it remains resistant to everything. the doctors at University are astonished i look as good as i do. thank you for reading this and for this web site.

Thank you for reaching out. Your physician is probably referring to the Alliance for Clinical Trials in Oncology. Here is their website:…

Contact information can be found here:…

Here is information about a trial using immunotherapy described in the article to treat soft tissue sarcoma, including contact information:…

Your treating physician would be the person who would enroll you in a trial if you are interested.

Can nivolumab (Opdivo™ be used as a first line treatment under "compassionate care" if an elderly patient with Stage IV melanoma with mets to kidneys and abdominal area instead of receiving ipilimumab (Yervoy™ first ? Thank you.

Thank you for reaching out. As a first step, we recommend your personal physician contact Dr. Jedd Wolchok at 646-497-9067 to discuss this further.

Otherwise, if you would like to make an appointment with a Memorial Sloan Kettering physician to discuss some of the many treatment options that are available for your case, please call our Physician Referral Service at
800-525-2225 or go to­care/appointment.

I have a really good friend that just can't seem to catch a break. He was diagnosed with crohn's disease some years back. I read that people with crohn's disease are at a higher risk for contracting skin cancer and just three months back he was diagnosed with melanoma. They did surgery and removed one lymph node but when the results came back they learned it had spread. They again did surgery to remove 4 other lymph nodes but to no prevail. He has been consulting with numerous physicians but no one will let him do chemo because of his crohn's disease. So pretty much they're just going to let him die. Is there anything he can do to save his life? Right now they're saying he has a 30 percent chance but I'm not buying that crap. Please let me know if you have any recommendations. Thanks!

Dear Matthew, we are sorry to hear about your friend. If he would like to make an appointment with one of our specialists to discuss his treatment options, please ask him to call our Physician Referral Service at 800-225-2225. Thank you for reaching out to us.

My 80 year old father is receiving excellent treatment at MSK for his squamous cell skin cancer. After two quite invasive surgeries, he is now about to undergo a combination of proton therapy and chemotherapy for skin cancer on his 7th cranial nerve. Would this kind of cancer be eligible for immunotherapy?

Melissa, we recommend you discuss this with his MSK team. Thank you for your comment, and glad to hear your father is receiving such good care.

My wife is current being treated for endometrial stream sarcoma at Sloan with standard care treatments. PD-1 expression is found in all gynecologic malignancies so this trial would seem to be a fit. Is this trial still open for new patients? What would be the best approach for follow up. Thank you.

MPS, we recommend you talk to your wife's medical team about the possibility of her participating in a clinical trial. Thank you for your comment.

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