Immunotherapy Combination Nivolumab Plus Ipilimumab Receives FDA Approval for Metastatic Melanoma

By Christina Pernambuco-Holsten

A doctor wearing a white lab coat writes on a white board with a marker.

Medical oncologist Jedd Wolchok pioneered a combination immunotherapy treatment for patients with advanced melanoma that has just been approved by the FDA.

Summary

The US Food and Drug Administration approved a combination immunotherapy treatment for people with metastatic melanoma. This means patients will now have access to the drug outside of clinical trials. MSK’s Jedd Wolchok created and tested the combination and lead the approval process.

Highlights
  • The FDA has approved combination ipilimumab-nivolumab therapy for people with advanced melanoma.
  • This means patients now have access to the treatment.
  • It’s the first combination immunotherapy treatment approved by the FDA.
  • The combination shows remarkable results and extends patients’ lives.

Today, the US Food and Drug Administration (FDA) approved the immunotherapy combination nivolumab (Opdivo®) plus ipilimumab (Yervoy®) for use in patients with metastatic melanoma. This is the first-ever combination immunotherapy to receive approval by the FDA. To learn more, we spoke with Memorial Sloan Kettering medical oncologist and cancer immunologist Jedd Wolchok, the physician-scientist leading this work.

Where did the idea to combine nivolumab and ipilimumab come from?

Video05:14
Find out how immunotherapy became one woman's best option for beating melanoma.

 The idea to combine these two immunotherapies emerged after we had strong scientific evidence that each one was effective by itself. We had worked with ipilimumab for several years, but it appeared to benefit only 20 percent of patients. Nivolumab had shown early signs of good activity for newly diagnosed patients, and a similar medicine (pembrolizumab) had activity in disease that was refractory — which means it wasn’t responding to treatment —  or relapsed after initial treatment with ipilimumab. Then there were lab experiments that showed the two strategies worked well together. So in 2010, before either drug had FDA approval on its own, we embarked on the phase I trial testing the combination of the two. Ultimately the results showed a 53 percent response rate — quite a bit higher than we expected. For some patients, it was very dramatic. We would get scans back showing that virtually all of the disease had gone away.

After the first 15 to 20 people, we began working with our colleagues at Bristol-Myers Squibb to design phase II and then phase III trials. The results of the phase II trial were presented in April during a meeting of the American Association for Cancer Research and published in the New England Journal of Medicine by my colleague Michael Postow, who was a fellow in our group back when we did the phase I trial. This past June, I presented the phase III results at the American Society of Clinical Oncology annual meeting.

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So it took five years from start to finish. That’s fast!

Yes, to me that’s the most exciting thing. We’ve gone from presenting the initial data to rolling this treatment out for standard use in quite a reasonably short period of time.

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What do you attribute this rapid pace to?

A few things. First, we saw an unmistakable signal when using the combination in patients. And these patients had a high unmet need — they didn’t have many other treatment options. Then there was exceptional coordination between the FDA, the academic investigators, and our industry colleagues. This example actually shows that drug development doesn’t necessarily require enormous studies with many years of follow-up. It’s possible to move at a much faster pace when everyone is collaborating effectively.

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Can you describe the moment you knew this combination was going to be a success?

By my desk, I have an email pinned up from one of our pathologists dated July 7, 2010. It has the pathology results from one of the very first patients to receive the regimen. This patient had a very large lump on his side, and every time he came in it got smaller and smaller. But after four doses, it wasn’t completely going away, and we wondered if the disease was resistant to treatment.

One of our surgeons, Mary Sue Brady, removed the lump, and I was so very eager to know what was going on that I waited outside the operating room while it was being removed. “What did it look like?” I asked her colleague when she came out. “Oh, just metastatic melanoma,” she said, and I was so disappointed.

Then, a week later, I got an email with the pathology report.

Completely necrotic tumor surrounded by immune cells — the histologic picture of treatment success.

In other words, the tumor was dead. I smiled, I printed it out, and it’s been hanging on my cork board ever since. And that was our second patient to receive the combination.

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As someone who has dedicated his career to improving treatment for people with advanced melanoma, what does this mean for you?

When I joined the MSK faculty in 2000, the median survival for patients with advanced melanoma was seven months with the best treatment available at that time. Now we are routinely hearing about two- and three-year survival. In the last study we did, we were seeing patients with 14 months of progression-free survival — which means they lived with their disease but it didn’t grow or spread — and that’s just an estimate. It gives you a flavor for how rapidly the expectations for life have changed, and it happened all within the first part of just one person’s career.

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How has MSK’s focus on collaboration and translational research made this advance possible?

MSK has had a tradition of excellence in treating melanoma and in developing novel therapies. Immunotherapy has actually been a focus at MSK since the late 1890s, and we have been a part of all the major immunotherapy advances throughout the history of cancer treatment.

For this particular regimen, we were among the very first to use this novel combination, we designed the pivotal studies that have supported approval, and we’ve done some of the most important research to understand who benefits and why. We haven’t answered all the questions yet, but we look forward to pursuing the answers and understanding how we use this regimen to help even more patients, for example those with lung cancer and other cancer types.

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Comments

Anonymous

Oct 1, 2015 • 5:34 PM

Does this treatment apply too choroid melanoma as well?

Memorial Sloan Kettering

Oct 5, 2015 • 9:27 AM

We forwarded your message to Dr. Wolchok, and he said this therapy is currently being tested on some patients with choroid melanoma, but it’s too early to report any data on the effectiveness. Thank you for your comment.

Anonymous

Oct 3, 2015 • 11:08 AM

My wife is having Gastro intestinal caner-adenocarcinocmo metastatic cecum- nodes in different part of stomach and liver. Can you suggest the treatment thorugh immunotherapy and its success and cost.

Anonymous

Oct 9, 2015 • 1:22 PM

Is there anything about this new treatment that can be used to prevent a recurrence of melanoma that was removed....I.e. A recurrence down the road that expresses itself in a different area of the body? Thank you...Linda Beach

Memorial Sloan Kettering

Oct 9, 2015 • 6:16 PM

Dear Linda, thanks so much for your question. The treatment is used for disease that has already recurred. Our doctors recommend that people who’ve been treated for melanoma have regular check-ups to monitor for recurrence and the development of other skin cancers.

You might also be interested to learn about our new 3-D total body photography program: https://www.mskcc.org/blog/3-d-photography-helps-early-detection-patien….

Thanks for your question!

Anonymous

Oct 10, 2015 • 9:06 AM

My dad is stage 4 melanoma. Has already taken Yervoy a few years ago, BRAF inhibitors, and also Keytruda. He is now showing signs of Keytruda resistance. Is he eligible for this drug combo?

Memorial Sloan Kettering

Oct 12, 2015 • 2:19 PM

Thank you for reaching out. We recommend that your father speak with his healthcare team about whether he this combination therapy would be appropriate for him. As the combination has now been FDA-approved, it might be a treatment option.

Lore Rasch

Nov 4, 2015 • 5:19 PM

I asked if there is or is being developed a targeted therapy for sickle cell anemia?

Memorial Sloan Kettering

Nov 4, 2015 • 5:46 PM

Not at Memorial Sloan Kettering. You might want to consult those sources to learn what other research centers are doing.

Janet

Apr 21, 2016 • 4:03 PM

My brother (lives in Denver) had a melanoma removed from his calf in 2013 with a follow up xray each April. About a month ago he felt a lump in his groin. He went to the doctor and they did: Chest xray, ct chest/abd/pelv, us abdomen, mri brain and tested his liver. The cancer returned to the chest, abodmen and in the groin is a tumor. His brain and liver are clean. They are now testing him for a gene to get him into a trial and we are also trying to get him to Dr. Rene Gonzalez in Denver. Are we doing everything we can?

Memorial Sloan Kettering

Apr 22, 2016 • 8:40 AM

Dear Janet, we are sorry to hear about your brother’s diagnosis. Only a physician who has examined your brother and reviewed his medical records can comment on whether all appropriate options are being explored. If he would like to make an appointment with one of our specialists for a second opinion, please ask him to call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

Stephen Allison Wald

Apr 27, 2016 • 3:08 PM

Dear Dr. Wolchok, Our daughter, Jennifer, has courageously fought neuroendocrine cancer for 13 years, via uncounted major surgeries, including a Whipple, two liver transplants, liver and pancreas resections, hip and femur replacements.
She has not had immunologic-based chemotherapy. She's experiencing multiple tumors around her body...fortunately, not yet in her lungs. No treatment options remain.
We can't help but wonder what the dangers might be for her to be treated with the combination protocol?
Godbless your pioneering work.

Memorial Sloan Kettering

Apr 27, 2016 • 5:00 PM

Dear Stephen, we are very sorry to hear about your daughter. She has been through so much. Unfortunately, our doctors can’t offer specific medical advice on our blog, but if you are interested in consulting with one of our specialists to discuss whether there are treatment options (including clinical trials) that may not yet have been explored, please call our Physician Referral Service. They can answer your questions and can be reached at 800-525-2225. Thank you for reaching out to us.

Sally

Jun 9, 2016 • 7:29 PM

Might this type of therapy be applicable to leukemia?

Memorial Sloan Kettering

Jun 15, 2016 • 11:27 AM

Dear Sally,
While this particular combination of immunotherapy drugs is not being tested in leukemia, several other immunotherapy approaches are. These include CAR T therapy, other checkpoint inhibitors, and stem cell transplants. Memorial Sloan Kettering has open clinical trials in all of these areas. If you would like to learn more, please visit https://www.mskcc.org/cancer-care/clinical-trials/search.

Thank you for your comment.

Linda Richardson

Jun 24, 2016 • 10:21 PM

Dear Drs, I have stage 4 mucosal melanoma. I've had my rectum and anus removed. I'm only 55 and have children and myself that are horrified. I want and need to live. I've had 6 doses of keytruda with mixed responses. I want to come there to see your melanoma specialists as I'm not sure what's going to happen. What about the combination of the two drugs or T cell therapy. I want the drastic treatment so I have a chance to live. I have 3 rumors in my pelvic area, there not going away, please researchers and melanoma experts at you center...help me, don't let me lose my children to this disease. You have more options than anyone there. Accept me and me live thru this, please, Sincerely, LindaRichardson

DOUG ENGLR

Aug 12, 2016 • 10:39 AM

Is there an online source where patients share their experience with the nivolumab or nivolumab plus treatment?

Memorial Sloan Kettering

Aug 16, 2016 • 9:46 AM

Doug, you might want to check out MSK’s online community, Connections. Patients there can share experiences about a range of cancer treatments and get advice from other patients and caregivers. It is open to all cancer patients, not just those being treated at MSK. To learn more, you can go to https://www.mskcc.org/experience/patient-support/counseling/groups/conn…. Thank you for your comment.

Stacy Hawn

Aug 17, 2016 • 7:39 PM

I am stage 3a melanoma. No complete lymph node dissection and only one positive for melanoma after my sentinel lymph node biopsy. Would I be able to get this combination therapy?

Memorial Sloan Kettering

Aug 18, 2016 • 4:57 PM

Stacy, thank you for reaching out. We recommend that you speak with your healthcare team about whether this combination therapy would be appropriate for you. If you are interested in consulting with one of our specialists, please call our Physician Referral Service. They can answer your questions and can be reached at 800-525-2225.

Valerie O'Brien

Sep 29, 2016 • 9:25 PM

My sister has neuroendocrine cancer and does not have the somatostatin receptor usually targeted in treatment. We found out today the chemo she has had for the past few months did not work and she has two tumors on her adrenal gland. Is anyone testing this combination (Nivolumab and Ipilimumab) therapy for neuroendocrine cancer?

Memorial Sloan Kettering

Sep 30, 2016 • 11:21 AM

Dear Valerie, we are sorry to hear about your sister’s diagnosis. You did not indicate whether she has gastrointestinal neuroendocrine cancer or pulmonary neuroendocrine cancer, so we have included links to both disease guides on our site for you to get more information about treatment options.

Pulmonary Neuroendocrine Tumors: https://www.mskcc.org/cancer-care/types/pulmonary-neuroendocrine-tumors

Gastrointestinal Neuroendocrine Tumors: https://www.mskcc.org/cancer-care/types/gastrointestinal-neuroendocrine

And here’s more information about Adrenal Gland Tumors: https://www.mskcc.org/cancer-care/types/adrenal-tumors

If she would like to make an appointment with one of our specialists to discuss her treatment options, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

Maor

Oct 13, 2016 • 5:05 AM

Dear Drs.
My brother is 43 years old.
Amonth and a half ago He was started to hobble on his left foot he got several medical tests and MRI the diagnosis melanoma with metastatic stage 4 to the brain.
he started for 5 times radio therapy FSR
to his brain every time a half hour radiation
also he got thrombosis on his left foot treated by Clexane injection twice a day
on the 11/10/16 my brother strat immunotherapy treatment by Opdivo for every 2 weeks
I would like to know how can my brother gets the treatment of the combinziia of Opdivo and YervoY ??
Please your kind help asap.
We are from Israel and my brother is treated in Sheba Medical Center
Thanks in advance !

Memorial Sloan Kettering

Oct 14, 2016 • 9:18 AM

Dear Maor, we are sorry to hear about your brother’s diagnosis. If you would like to arrange for one of our specialists to conduct a medical records review by mail or an in-person appointment to discuss possible treatment recommendations, please contact our International Center at international@mskcc.org. To learn more about our services for patients who live outside of the United States, please visit https://www.mskcc.org/experience/become-patient/international-patients. Thank you for reaching out to us.

David Sochol

Oct 29, 2016 • 11:22 PM

Does this (ipi and novi) work for SCLC or advanced carcinoid/pulmonary NET?

Memorial Sloan Kettering

Oct 31, 2016 • 10:54 AM

Dear David, the ipi + nivo has been studied in SCLC, where it has shown promise, but the combination is not FDA approved for this indication, or NET. You can read more about some clinical trial results here: https://am.asco.org/pd-1-agents-show-promise-small-cell-lung-cancer

To learn about a current, ongoing trial of this combination, please visit: https://www.mskcc.org/cancer-care/clinical-trials/15-303. If you have any questions about these studies or would like to make an appointment with one of our specialists, please call our Physician Referral Service at 800-525-2225.

Thank you for reaching out to us.

Sol

Jan 6, 2017 • 5:59 PM

my father was a patient there he recently died feb 10 2016. the duo treatment didn't help because of his immune system because of HIV. are you guys trying to also find ways to treat HIV patient another way to boost the immune system. by the way memorial Sloan gave the best treatment to my father but his immune was weak and stage 5. And I thank you for that.

Memorial Sloan Kettering

Jan 9, 2017 • 12:14 PM

Dear Sol,
We’re sorry to hear about your father, but we are glad to hear he was well
cared for. To answer your question, yes, researchers are very interested
in using new immunotherapy approaches as a way to fight infectious
diseases like HIV. Here is one study that MSK researchers are pursuing:

https://www.mskcc.org/cancer-care/clinical-trials/16-1286

Thank you for your comment.

Jen

Feb 17, 2017 • 7:24 PM

We just found out that my husband has melanoma in lungs. He had melanoma in 2010 on his arm. It was removed, no treatment was done then. His mass is 7.4by 5.4 cm. We schedule appt to melanoma doctor next week. We will do pt scan on Monday before visit. His byopcy cells were sent to lab for mutation DNA, hopefully today. What will be your recommendations?

Linda

Mar 14, 2017 • 3:00 PM

My sister has malignant melanoma of the groin. Receiving yervoy had 3 tx then has become very ill Fevers,sinus infection cough just diagnosed with colitis. After 2 hospitalizations found drug induced colitis. Started on steroid regime. Question should she receive 4th dose of yervoy?

Memorial Sloan Kettering

Mar 15, 2017 • 5:27 PM

Dear Linda. we’re sorry to hear about your sister’s diagnosis and the side effects from her treatment. Unfortunately we are not able to offer medical advice on our blog, so we are not able to say what treatment may be appropriate for her. We recommend that you discuss this with her healthcare team. If she wants to come to MSK for a consultation, she can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment, and best wishes to you.

Lisa Gutschow

Mar 21, 2017 • 3:22 PM

After failing Ipi and Keytruda, would the Ipi/Nivo combo be an option for me?

Memorial Sloan Kettering

Mar 21, 2017 • 3:53 PM

Dear Lisa, we’re sorry but we are not able to answer individual medical questions on our blog. We recommend that you discuss this with your healthcare team. If you’re interested in having a consultation with an MSK doctor, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment, and best wishes to you.

Kimberly M

Jun 15, 2017 • 6:48 PM

Hello!
Recently had a mole removed from my right shoulder, it was stage 2. Melanoma. Tumor removed with wide margins, clean border. The Sentinel Node was Removed under arm and positive for melanoma, but it was very small. PET scan clear, MRI clear. I've read a lot about axillary lymph node dissection and really concerned for lifelong problems. I feel as if I already have issues from the sentinel node was removed. Are there any alternatives to this standard protocol? They want to do the axillary lymph node dissection with additional treatment TBD. My concern is that im already prone to edema at times and why set myself up for more problems down the road? With all this technology, there are no alternatives to check and see if they are positive? Best, Kim

Memorial Sloan Kettering

Jun 19, 2017 • 12:30 PM

Dear Kimberly,
We are not able to make treatment recommendations for individual patients on our blog, since each case is different. However, you may be interested in this recent blog post about a study that compared immediate lymph node dissection to a watch-and-wait approach: https://www.mskcc.org/blog/definitive-study-shows-people-melanoma-do-no….

If you would like to consult with an MSK doctor, we encourage you to make an appointment at 800-525-2225 or request an appointment online at https://www.mskcc.org/experience/become-patient/appointment. Thank you for your comment.

Patty Torrilhon

Oct 8, 2017 • 3:51 PM

My husband was diagnosed 6 months ago with primary anal/rectal malignant melanoma. A surgeon perfomed an excision of the 3cm tumor. Cancer cells remained in the muscle wall. He was scheduled for 6 chemo treatments (cisplatin) which had to be terminated after immediate damage to his kidneys. He then received 33 radiation treatments. During this time he suffered from a severe body rash which was biopsed with a probable drug reaction diagnosis. He was given prednisone which worked at a high does, but returns as soon as the medication stops. He has told that his prognosis is poor and that his cancer cells do not have the characteristics needed for immuno-therapies? He is scheduled for a follow up PET scan in November. We have been told that this cancer is extremely rare and so options are not very available. Do you have suggestions for us? Thank you.

Memorial Sloan Kettering

Oct 9, 2017 • 8:31 AM

Dear Patty, we’re very sorry to hear that your husband is going through this. If he would like to come to MSK for a consultation, and to learn if he would qualify for any of our clinical trials, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information. If you are not in the NYC area and not able to come to MSK, you may want to seek out a National Cancer Institute-designated cancer center that is closer to where you live. You can find a list at https://www.cancer.gov/research/nci-role/cancer-centers

Thank you for your comment, and best wishes to you and your husband.

Backindaday

Jul 9, 2018 • 9:13 AM

it seems to me, that this therapy might exacerbate MS attacks. were any MS patients included in the trial?

MONTE JEFFERY

Dec 19, 2018 • 1:47 PM

What risks does a patient with one kidney have when given the combo ipi/nivo for rectal melanoma excised once, but back a year later?

Memorial Sloan Kettering

Dec 19, 2018 • 4:10 PM

Dear Monte, this is something that you should discuss with a physician who is familiar with the patient’s entire medical history. Thank you for your comment and best wishes to you.

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