Ipilimumab + Nivolumab for Melanoma

Recruiting at 1 trial location

Overseen By Zachary Buchwald, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Immunosuppressants

Disqualifiers: Active autoimmune, Leptomeningeal, 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: 6

Duration: 2 years

99 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the time of day affects the effectiveness of two drugs, ipilimumab and nivolumab, for treating stage IV melanoma that cannot be surgically removed. These drugs are a type of immunotherapy, which uses the body's immune system to fight cancer. Researchers aim to determine if taking these medications earlier in the day improves their effectiveness and patient survival. Individuals with advanced melanoma that cannot be surgically removed, who have not recently undergone immunotherapy, and have stable brain metastases might be suitable candidates for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive drugs or have an active autoimmune disease, you may not be eligible to participate.

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

Studies have shown that combining ipilimumab and nivolumab can help treat advanced melanoma. However, safety concerns exist for some patients. In a study with 709 participants, about half (50.7%) experienced serious side effects, known as grade 3-4 adverse events, which are severe reactions to the treatment. Despite these risks, many patients still benefit from this combination.

This combination has been used for some time, and both drugs are approved for treating advanced melanoma, indicating thorough testing. However, individual reactions vary, so discussing potential risks and benefits with a healthcare provider is crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Ipilimumab and Nivolumab for melanoma treatment because this duo offers a unique approach to tackling cancer. Most melanoma treatments focus on either targeting cancer cells directly or boosting the immune system in a general way. However, Ipilimumab and Nivolumab work together to block specific proteins, CTLA-4 and PD-1, which can help unleash the immune system's full potential against cancer cells. This dual-action can enhance the body's ability to detect and destroy melanoma cells more effectively than typical treatments. This innovative strategy holds promise for improving outcomes in patients with advanced melanoma.

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

Research has shown that using ipilimumab and nivolumab together can help people with advanced melanoma live longer. One study found that 52% of patients who received this combination were still alive after five years, compared to 26% of those who only received ipilimumab. Another study found that patients with no cancer progression after three years had a 96% chance of being alive at ten years. This combination appears to help the immune system fight cancer more effectively than using either drug alone. In this trial, participants will receive the combination of ipilimumab and nivolumab, indicating that this regimen can be a strong treatment option for melanoma. ^{3 6 7 8 9}

Who Is on the Research Team?

Michael Lowe, MD, MA

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with stage IV melanoma or melanoma that can't be surgically removed. Participants must be eligible to receive immunotherapy and willing to undergo various assessments, including biopsies, imaging tests, and questionnaires.

Inclusion Criteria

My melanoma is stage IV and cannot be removed with surgery.

I have small, symptom-free brain tumors less than 2 cm.

I haven't had immunotherapy in the last year, but BRAF/MEK inhibitors are okay.

Exclusion Criteria

I have cancer that has spread to the lining of my brain and spinal cord.

I do not have eye melanoma.

I am not taking more than 10mg of prednisone daily.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab and ipilimumab at specified times of day for 4 cycles, followed by maintenance nivolumab for up to 2 years

2 years

Every 3 weeks for 4 cycles, then regular visits for maintenance

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 12 months, then up to year 5

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab

Trial Overview The TIME Trial is testing the effectiveness of administering two immune-boosting drugs, Ipilimumab and Nivolumab, at different times of day. The goal is to see if taking these medications in the morning leads to better outcomes than other times.

How Is the Trial Designed?

Group I: Arm II (nivolumab, ipilimumab) Experimental Treatment 8 Interventions

Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes at 1100-1400 on day 1 of each cycle. Cycles repeat every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance nivolumab for up to a total of 2 years. Patients wear an actigraphy device for 5-7 days at enrollment prior to first infusion and for up to 4 weeks then over 3 weeks starting with visit 4. Patients also undergo check swab and blood sample collection, CT or MRI and MRI or CT of brain throughout the study. Additionally, patients may optionally undergo tumor tissue biopsy throughout the study.

Group II: Arm I (nivolumab, ipilimumab) Experimental Treatment 8 Interventions

Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes at 0800-1100 on day 1 of each cycle. Cycles repeat every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance nivolumab for up to a total of 2 years. Patients wear an actigraphy device for 5-7 days at enrollment prior to first infusion and for up to 4 weeks then over 3 weeks starting with visit 4. Patients also undergo check swab and blood sample collection, CT or MRI and MRI or CT of brain throughout the study. Additionally, patients may optionally undergo tumor tissue biopsy throughout the study.

Group III: Arm III (nivolumab, ipilimumab) Active Control 8 Interventions

Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes at 1400-1700 on day 1 of each cycle. Cycles repeat every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance nivolumab for up to a total of 2 years. Patients wear an actigraphy device for 5-7 days at enrollment prior to first infusion and for up to 4 weeks then over 3 weeks starting with visit 4. Patients also undergo check swab and blood sample collection, CT or MRI and MRI or CT of brain throughout the study. Additionally, patients may optionally undergo tumor tissue biopsy throughout the study.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. 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 ...

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. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00400

Pooled Long-Term Outcomes With Nivolumab Plus ... Patients in these equivalent subgroups who had been treated with NIVO + IPI had 5-year OS rates of 66%, 64%, and 36%, respectively. Open in ...

4. news.bms.com news.bms.com/news/details/2021/Six-and-a-Half-Year-Outcomes-for-Opdivo-nivolumab-in-Combination-with-Yervoy-ipilimumab-Continue-to-Demonstrate-Durable-Long-Term-Survival-Benefits-in-Patients-with-Advanced-Melanoma/default.aspx

Six-and-a-Half-Year Outcomes for Opdivo (nivolumab) in ... Of the 49% of patients alive and in follow-up, 77% of patients who received the combination (112/145), 69% of Opdivo-treated patients (84/122) ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2772611825000060

Selecting first-line immunotherapy in advanced melanoma In BRAF WT disease, ipilimumab-nivolumab and nivolumab had similar outcomes (5-year PFS: 35 % vs 32 %, 5-year OS: 48 % vs 43 %, 10-year OS: 39 % vs 37 %).

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

Long-Term Outcomes With Nivolumab Plus Ipilimumab or ... Durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma.

8. 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 ... In melanoma patients, combined nivolumab plus ipilimumab therapy demonstrates superior efficacy in terms of survival and adverse events compared to monotherapy.

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

Long-term outcomes among patients who respond within ... Patients with a PR within 12 months of nivolumab+ipilimumab treatment appeared to have better 5-year outcomes than those who received nivolumab alone for both ...