Nivolumab + Ipilimumab for Melanoma

Not currently recruiting at 2 trial locations

Overseen By Tara Mitchell

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center at Penn Medicine

Must not be taking: Immunosuppressants, Steroids, Live vaccines

Disqualifiers: Unresectable disease, Active infection, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining two treatments, nivolumab and ipilimumab, for individuals with surgically removable melanoma. Participants will receive nivolumab before surgery and, based on the surgery results, will continue with either nivolumab alone or a combination of nivolumab and ipilimumab for up to a year. Suitable candidates have melanoma that can be surgically removed and have not previously received certain immune therapies. As a Phase 2 trial, the research focuses on assessing the treatment's efficacy in an initial, smaller group of participants.

Do I have to stop taking my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or have received certain treatments recently, you may not be eligible. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using nivolumab and ipilimumab together is generally safe for people with melanoma. One study found that this combination helped about 52% of participants live for five years, which is very encouraging.

Regarding safety, other studies report that about 2.5% of patients experienced infusion-related reactions, such as allergic reactions. This indicates that most people handled the treatment well.

This trial is testing the treatment in a new way. Since the FDA has already approved nivolumab and ipilimumab for other uses, they have a known safety record. However, like any treatment, there can be risks. Always discuss any concerns with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Nivolumab and Ipilimumab are immunotherapies that harness the body's own immune system to fight melanoma, a type of skin cancer. Unlike traditional treatments that directly target cancer cells, these drugs target proteins that prevent the immune system from attacking cancer, essentially removing the brakes on the immune response. Nivolumab blocks the PD-1 protein, while Ipilimumab targets CTLA-4, both of which are pathways that tumors exploit to evade immune detection. This dual-action approach could potentially lead to more robust and longer-lasting responses compared to standard chemotherapy or targeted therapies.

What evidence suggests that this trial's treatments could be effective for melanoma?

Research shows that using nivolumab and ipilimumab together effectively treats melanoma, a type of skin cancer. In this trial, participants in Arm C will receive this combination. Previous clinical trials demonstrated that patients receiving both drugs had a 58% lower chance of cancer spreading or worsening compared to those taking only ipilimumab. The five-year survival rates were also higher for those on the combination treatment, with 52% surviving, compared to 44% for those on nivolumab alone and 26% for those on ipilimumab alone. Additionally, after 10 years, the combination treatment continued to benefit many patients, with significant tumor shrinkage. These findings suggest that using nivolumab and ipilimumab together offers a strong chance of controlling melanoma. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults over 18 with stage III resectable melanoma can join this trial. They must be in good health, not pregnant or breastfeeding, and willing to use effective contraception. People with certain medical conditions, recent transfusions, active infections, or those on immunosuppressive drugs cannot participate.

Inclusion Criteria

Either the subject or the subject's legally authorized representative must be willing and able to provide written informed consent before the performance of any protocol-related procedures.

I am fully active or restricted in physically strenuous activity but can do light work.

I agree to follow the study's contraceptive advice for 7 months after my last medication dose.

Exclusion Criteria

Prisoners or subjects who are involuntarily incarcerated.

I have or had lung inflammation that needed steroids.

I have been treated with specific immune system targeting drugs before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive one dose of nivolumab 480 mg IV

4 weeks

1 visit (in-person)

Surgery

Participants undergo standard definitive surgery

1 day

1 visit (in-person)

Adjuvant Treatment

Participants receive open-label treatment with nivolumab or ipilimumab plus nivolumab based on pathologic response

1 year

Every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 7 years

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab

Trial Overview The study tests nivolumab as a pre-surgery (neoadjuvant) treatment for melanoma. After surgery to remove the cancer, patients get either more nivolumab or a combination of nivolumab and ipilimumab for up to one year based on their response to the initial treatment.

How Is the Trial Designed?

Group I: Arm C: Adjuvant Combination (Less than Complete Response) Experimental Treatment 2 Interventions

ipilimumab (1mg/kg) plus nivolumab (3mg/kg) for 4 doses and then nivolumab (480 mg) alone for a total of one year

Group II: Arm A: Adjuvant Nivolumab (Complete Pathological Response) Active Control 1 Intervention

480 mg IV for up to one year

Group III: Arm B: Adjuvant Nivolumab (Less than Complete Response) Active Control 1 Intervention

480 mg IV for up to one year

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Citations

1. opdivo.com opdivo.com/melanoma/clinical-trial-results/advanced-immunotherapy-combination

Advanced Melanoma Skin Cancer | Clinical Trial Results In the clinical trial, people given OPDIVO + YERVOY had a 58% lower risk of their cancer spreading, growing, or getting worse than those given YERVOY alone.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1910836

Five-Year Survival with Combined Nivolumab and ... Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group.

3. news.bms.com news.bms.com/news/details/2024/Bristol-Myers-Squibb-Presents-Landmark-10-Year-Follow-Up-Data-from-CheckMate--067-Which-Showed-Continued-Durable-Long-Term-Survival-Benefit-with-Opdivo-plus-Yervoy-in-Advanced-Melanoma/default.aspx

067 Which Showed Continued Durable Long-Term ... In addition, at 10 years of follow up, the Opdivo plus Yervoy combination showed melanoma-specific survival (MSS) rates of 52% (median not ...

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

Nivolumab (Opdivo) + Ipilimumab (Yervoy) The results mean that more patients taking the combination therapy experienced melanoma tumor shrinkage if they received nivolumab and ipilimumab versus ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7757740/

Safety and efficacy of combination nivolumab plus ... In this EAP, nivolumab plus ipilimumab demonstrated high survival rates and safety outcomes consistent with those from randomized clinical trials, further ...

6. opdivohcp.com opdivohcp.com/safety/melanoma/opdivo-yervoy

OPDIVO® (nivolumab) + YERVOY® (ipilimumab) Safety in ... In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In HCC ...