Ipilimumab + Nivolumab for Melanoma

Not currently recruiting at 17 trial locations

Overseen By Michael Postow, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of using two drugs, ipilimumab and nivolumab, to treat melanoma, a type of skin cancer that has spread and cannot be surgically removed. The study aims to determine if two doses of these drugs can be as effective as the usual four doses. If a participant shows early signs of improvement, they might switch to nivolumab alone for maintenance. If there is no early benefit, additional doses may be administered based on the patient's needs. This trial may suit those with advanced melanoma that cannot be surgically removed and who have not received certain prior treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them at least 14 days before starting the study drugs.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of ipilimumab and nivolumab has been well-studied in people with melanoma, a type of skin cancer. One study found that about half of the patients (50.7%) experienced serious side effects, which were quite severe. These side effects are common for this kind of cancer treatment. Another study found that people who responded well to the treatment had a much better chance of living longer. Specifically, 82% of those who responded were still alive five years later, compared to 40% of those who did not respond.

While these treatments can be effective, it's important to be aware of the potential for serious side effects. Doctors and researchers understand these risks and closely monitor patients during trials. Prospective participants should discuss these findings with their doctor to understand what to expect and decide if this treatment is suitable. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for melanoma?

Researchers are excited about the combination of Ipilimumab and Nivolumab for treating melanoma because it represents a powerful duo in immunotherapy. Unlike traditional treatments like surgery, radiation, or chemotherapy that target the tumor directly, this combination harnesses the body's immune system to fight cancer. Ipilimumab and Nivolumab work by blocking specific proteins that prevent immune cells from attacking cancer cells, potentially leading to a more robust and sustained antitumor response. This approach might offer a new avenue for patients who do not respond well to existing treatments, providing hope for more effective long-term control of melanoma.

What evidence suggests that the ipilimumab and nivolumab combination immunotherapy could be effective for melanoma?

Research has shown that using ipilimumab and nivolumab together can effectively treat advanced melanoma. In this trial, participants will receive this combination therapy. Studies have found that patients alive and without disease progression after three years had a 96% chance of surviving melanoma over ten years with this combination. The combination therapy outperforms using either drug alone. Although there is a higher chance of needing hospital care early in treatment, the long-term survival benefits are significant. This combination offers lasting survival benefits, making it a strong option for treating melanoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael A. Postow

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with unresectable stage III or IV melanoma who haven't had CTLA-4 or PD-1/PD-L1 therapy. They must have a life expectancy of at least 4 months, be in good physical condition (ECOG 0-1), and women must use effective contraception. Exclusions include severe allergies, mental impairments, other serious illnesses, active autoimmune diseases requiring steroids or immunosuppressants, certain neuropathies, another active cancer, known immunodeficiency or viral hepatitis.

Inclusion Criteria

My melanoma cannot be removed by surgery and is stage III or IV.

I haven't received CTLA-4 or PD-1/PD-L1 therapy for my metastatic disease.

I use two birth control methods and will continue for 23 weeks after my last treatment dose.

Exclusion Criteria

I don't have another cancer that needs treatment or affects melanoma tests.

I am able to understand and follow the study's requirements.

I do not have any serious illnesses like infections needing antibiotics or bleeding disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive 2 doses of ipilimumab 3mg/kg + nivolumab 1mg/kg every 3 weeks

6 weeks

2 visits (in-person)

Response Assessment

Participants are assessed for antitumor effect by RECIST at week 6

1 week

1 visit (in-person)

Maintenance Treatment

Participants with favorable response receive maintenance nivolumab 480mg every 4 weeks for 2 doses

4 weeks

2 visits (in-person)

Extended Treatment

Participants without favorable response receive additional ipilimumab + nivolumab every 3 weeks, reassessed at week 12

6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab and Nivolumab Combination Immunotherapy

Trial Overview The study tests if two doses of ipilimumab plus nivolumab are as effective as the usual four doses for patients showing early benefits from treatment. Patients without early benefit can continue receiving additional doses beyond the standard four if deemed beneficial.

How Is the Trial Designed?

Group I: ipilimumab and nivolumab Experimental Treatment 2 Interventions

Pts will receive 2 doses of ipilimumab 3mg/kg + nivolumab 1mg/kg every 3 weeks. Week 6, if pts have achieved a favorable antitumor effect by RECIST will begin maintenance nivolumab alone at 480mg every 4 weeks for 2 doses (week 6 \& week 10) \& repeat response assessments at week 12. If pts don't achieve a favorable antitumor effect at week 6, pt will get 2 additional doses of ipilimumab + nivolumab every 3 weeks \& then will be assessed for response at week 12. If pts haven't achieved a favorable antitumor effect by week 12, if felt in the best interest for the pt as determined by the PI, pts may continue getting additional doses of ipilimumab + nivolumab with response reassessments after every 2 doses. Maintenance nivolumab will continued until unacceptable toxicity or confirmed disease progression. If pts have had an initial clinical benefit from therapy \& subsequently experience progressive disease at any time, reinduction with combination ipilimuma+ nivolumab will be allowed.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a phase 1 trial involving 53 patients with advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 40% objective response rate, with 65% of patients showing clinical activity, indicating significant effectiveness in tumor reduction.

The concurrent treatment had a manageable safety profile, with 53% of patients experiencing grade 3 or 4 adverse events, which were similar to those seen with monotherapy and generally reversible, suggesting that this combination therapy is a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in advanced melanoma. Wolchok, JD., Kluger, H., Callahan, MK., et al.[2022]

In a phase 3 trial with patients suffering from advanced melanoma, the combination of nivolumab and ipilimumab resulted in significantly longer overall survival rates (58% at 3 years) compared to ipilimumab alone (34%).

The safety profile of the combination therapy was consistent with previous reports, showing that 59% of patients experienced severe treatment-related adverse events, indicating that while effective, the combination therapy has a higher risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. Wolchok, JD., Chiarion-Sileni, V., Gonzalez, R., et al.[2023]

Ipilimumab has shown a positive impact on overall survival in patients with stage IV melanoma, with long-term follow-up indicating its effectiveness compared to conventional treatments.

While 84.8% of patients experience drug-related adverse events, most are mild to moderate; however, severe reactions can occur, necessitating careful monitoring and management, especially when combined with other therapies like vemurafenib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. Camacho, LH.[2022]

Combining nivolumab and ipilimumab shows improved effectiveness in treating metastatic melanoma compared to using either drug alone, based on a retrospective analysis of approximately 7700 patients.

The combination therapy presents a safety profile that includes immune-related adverse events from both drugs, indicating that while the combination is effective, it also carries a heightened risk of toxicity that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. Soldatos, TG., Dimitrakopoulou-Strauss, A., Larribere, L., et al.[2022]

In a meta-analysis of 2,946 cancer patients, the combination therapy of nivolumab and ipilimumab was found to significantly increase the risk of immune-related adverse events (irAEs) compared to nivolumab alone.

Patients receiving the combination therapy experienced higher rates of various irAEs, including skin reactions, gastrointestinal issues, and liver enzyme elevation, indicating a need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of immune-related adverse events associated with ipilimumab-plus-nivolumab and nivolumab therapy in cancer patients. Zhou, S., Khanal, S., Zhang, H.[2022]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

Combining nivolumab with ipilimumab results in higher response rates in cancer treatment compared to using nivolumab alone, indicating a potentially more effective therapeutic strategy.

This combination therapy may enhance the immune response against cancer, but specific details on the number of subjects or study duration are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

The combination of nivolumab and ipilimumab, two immune checkpoint inhibitors, is a promising treatment for advanced melanoma, enhancing the body's immune response against the cancer.

Adding denosumab to this treatment may further improve anti-tumor effects by counteracting the immunosuppressive environment created by CD8+ T cells, as suggested by recent reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Multiple Metastatic Melanoma with Nivolumab, Ipilimumab plus Denosumab Combined Therapy. Yoshida, S., Fujimura, T., Kambayashi, Y., et al.[2020]

In a phase 2 trial involving 142 patients with untreated advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 2-year overall survival rate of 63.8%, compared to 53.6% for those receiving ipilimumab alone, suggesting improved survival outcomes with the combination therapy.

However, the combination treatment was associated with a higher incidence of severe side effects, with 54% of patients experiencing grade 3-4 adverse events compared to 20% in the ipilimumab-only group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Hodi, FS., Chesney, J., Pavlick, AC., et al.[2022]

In a study of 142 patients with advanced melanoma, the combination of nivolumab and ipilimumab resulted in a significantly higher objective response rate of 61% compared to 11% for ipilimumab alone, indicating that the combination therapy is much more effective for treating this type of cancer.

While the combination therapy showed promising efficacy, it also had a higher incidence of severe adverse events (54% vs. 24% for monotherapy), but most of these side effects were manageable with immune-modulating medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. Postow, MA., Chesney, J., Pavlick, AC., et al.[2022]

In a study of 1255 patients with metastatic non-small cell lung cancer (NSCLC), first-line treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a high incidence of treatment-related adverse events (TRAEs), with 78% experiencing any-grade TRAEs and 34% experiencing severe (grade 3 or 4) TRAEs, but the treatment was generally well tolerated.

Patients who discontinued NIVO+IPI due to TRAEs still had a favorable long-term survival rate, with a 3-year overall survival of 50%, indicating that stopping treatment because of side effects did not negatively impact their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. Paz-Ares, LG., Ciuleanu, TE., Pluzanski, A., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39282897/

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in ... Among patients who had been alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% with nivolumab plus ipilimumab, 97 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12080919/

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in ... In patients who were progression-free at 3-years, 10-year melanoma-specific survival rates were 96% with nivolumab-plus-ipilimumab, 97% with ...

3. curemelanoma.org curemelanoma.org/patient-eng/melanoma-treatment/options/nivolumab-opdivo-ipilimumab-yervoy

Nivolumab (Opdivo) + Ipilimumab (Yervoy) When used together, nivolumab and ipilimumab can treat advanced melanoma more effectively than each drug on its own.

4. asco.org asco.org/abstracts-presentations/ABSTRACT368728

Real-world comparison of outcomes in ... Patients treated with the combination therapy had 5-fold more hospitalizations during the first 90 days after the treatment start (46% vs 10%, p = 3e-22).

5. onclive.com onclive.com/view/nivolumab-alone-with-ipilimumab-demonstrate-sustained-10-year-survival-benefit-in-advanced-melanoma

Nivolumab Alone, With Ipilimumab Demonstrate Sustained ... Nivolumab (Opdivo) alone or combined with ipilimumab (Yervoy) showed a significant and durable benefit in overall and melanoma-specific survival (MSS) at 10 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37103470/

Real-world Outcomes of Ipilimumab Plus Nivolumab ... In total, 709 patients received first-line ipilimumab plus nivolumab. Three hundred sixty (50.7%) patients experienced grade 3-4 adverse events, ...

7. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2407417

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab ... Among patients who had been alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% with nivolumab plus ipilimumab, 97 ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02229

Long-Term Outcomes With Nivolumab Plus Ipilimumab or ... We present 6.5-year results from CheckMate 067, including a first report of melanoma-specific survival. Knowledge Generated. Prolonged survival ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S095980492401726X

Long-term outcomes among patients who respond within ... In 12-month landmark analyses, 5-year OS rates for responders versus non-responders were 82 % versus 40 % with nivolumab+ipilimumab (HR=0.23 [95 % CI, 0.15–0.35]) ...

10. journals.lww.com journals.lww.com/atmr/fulltext/2024/10000/safety_and_efficacy_of_combined_nivolumab_plus.5.aspx

Safety and Efficacy of Combined Nivolumab Plus ... Our analysis revealed that combined nivolumab plus ipilimumab therapy demonstrated a superior safety and efficacy profile compared to monotherapy in melanoma ...