Pembrolizumab + Ipilimumab for Melanoma

Not currently recruiting at 9 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must be taking: Anti-PD1/L1 antibodies

Must not be taking: Systemic steroids, Immunosuppressives

Disqualifiers: Active TB, Autoimmune disease, 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: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments: pembrolizumab (an immunotherapy drug known as KEYTRUDA) and ipilimumab (another immunotherapy drug known as Yervoy). The aim is to evaluate their combined effectiveness against advanced melanoma, a serious type of skin cancer. The trial seeks to determine how many patients respond to the treatment and how long it takes before the cancer worsens. Researchers also aim to identify blood or tumor factors that might predict who will benefit from this combination. Individuals whose melanoma has stopped responding or progressed after previous treatment might be suitable for this trial. 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, you cannot participate if you are on systemic steroid therapy or other immunosuppressive treatments within 7 days before starting the trial.

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

Research has shown that the combination of pembrolizumab and ipilimumab for melanoma has been studied extensively. Studies have found that this combination can extend the lives of patients with advanced melanoma. Past reports indicate that this treatment is generally well-tolerated in terms of safety.

Long-term data suggest that many patients have lived longer after receiving pembrolizumab, with over one-third still alive after ten years. This marks a significant improvement compared to those who only received ipilimumab. However, like all treatments, side effects can occur.

Previous studies reported side effects such as fatigue and skin problems in some patients. While this might sound concerning, these treatments have been used for some time, and doctors have gained significant experience in managing these effects.

Overall, the combination of pembrolizumab and ipilimumab has shown promise in treating melanoma and has a well-studied safety profile. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for melanoma?

Researchers are excited about the combination of pembrolizumab and ipilimumab for treating melanoma because it offers a novel approach by harnessing the power of the immune system. Unlike traditional treatments such as chemotherapy, which directly target cancer cells, pembrolizumab and ipilimumab are immune checkpoint inhibitors. Pembrolizumab blocks the PD-1 pathway, while ipilimumab targets CTLA-4, both of which are proteins that can stop the immune system from attacking cancer cells effectively. By combining these two, the treatment potentially enhances the body's natural ability to fight melanoma more efficiently. This dual mechanism of action is why researchers are hopeful for better outcomes and prolonged survival for patients.

What evidence suggests that this treatment might be an effective treatment for melanoma?

Research has shown that using pembrolizumab and ipilimumab together appears promising for treating advanced melanoma, a type of skin cancer. In one study, 34% of patients treated with pembrolizumab survived for 10 years, outperforming those treated with ipilimumab alone. On average, patients lived about 51.9 months with pembrolizumab, compared to 17.2 months with ipilimumab. This trial will evaluate the combination of these drugs, aiming to enhance the immune system's ability to fight cancer, potentially leading to better outcomes. ^{1 2 3 5 6}

Who Is on the Research Team?

Thomas Gajewski, M.D.

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma who've seen their cancer progress or remain stable after at least 24 weeks on anti-PD1/L1 therapy, or within 6 months of adjuvant anti-PD1. They must be in good health otherwise, not pregnant, willing to use birth control, and have no history of severe allergies to the drugs being tested or certain other medical conditions.

Inclusion Criteria

Be willing and able to provide written informed consent for the trial

I have taken a pregnancy test in the last 72 hours and it was negative.

My cancer progressed or didn't worsen for 24 weeks on anti-PD1/L1 treatment, or it worsened within 6 months after adjuvant anti-PD1 therapy.

Exclusion Criteria

I have a history of active tuberculosis.

I do not have eye melanoma.

I have an immune system disorder or have been on steroids or other immune-weakening medicines in the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the combination of pembrolizumab and ipilimumab

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Pembrolizumab

Trial Overview The study tests a combination of two immunotherapy drugs: Pembrolizumab (anti-PD1) and Ipilimumab (anti-CTLA4), following prior treatment with an anti-PD1/L1 antibody. It aims to see how well this combo works against melanoma by measuring tumor response and tracking how long patients live without their disease getting worse.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 2 Interventions

Treatment with the combination of pembrolizumab and ipilimumab.

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

A 45-year-old male with metastatic melanoma experienced severe immune-related adverse events from ipilimumab, leading to its discontinuation, but successfully transitioned to pembrolizumab.

After over 20 months of treatment with pembrolizumab, the patient has shown no major toxicities and has achieved an ongoing partial response, suggesting that pembrolizumab may be a safe and effective option for patients with prior severe adverse events from other immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in a BRAF-mutant metastatic melanoma patient following a severe immune-related adverse event with ipilimumab. Aya, F., Fernández-Martínez, A., Gaba, L., et al.[2017]

In a post hoc analysis of the KEYNOTE-006 study involving 555 patients with advanced melanoma, both ipilimumab and BRAF ± MEK inhibitors showed antitumor activity as subsequent therapies after pembrolizumab, with overall response rates (ORR) of 17.5% for ipilimumab and 30.5% for BRAF ± MEK inhibitors.

Patients who had not previously received BRAF ± MEK inhibitors showed a significantly higher ORR of 43.2% when treated with these agents after pembrolizumab, indicating that prior treatment status may influence the effectiveness of subsequent therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006. Long, GV., Arance, A., Mortier, L., et al.[2022]

Pembrolizumab (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Citations

1. merck.com merck.com/news/ten-year-data-for-mercks-keytruda-pembrolizumab-demonstrates-sustained-overall-survival-benefit-versus-ipilimumab-in-advanced-melanoma/

Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534%2824%2903910-3/fulltext

10-year follow-up of the phase III KEYNOTE-006 study Median melanoma-specific survival was 51.9 months (95% CI 30.0-114.7 months) for pembrolizumab and 17.2 months (13.9-25.9 months) for ipilimumab ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37348035/

Seven-Year Follow-Up of the Phase III KEYNOTE-006 Study Median modified progression-free survival (mPFS) was 9.4 months for pembrolizumab versus 3.8 months for ipilimumab; 7-year mPFS was 23.8% and ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0923753424039103

10-year follow-up of the phase III KEYNOTE-006 study The 10-year follow-up of KEYNOTE-006 confirms that pembrolizumab provides long-term survival benefit in advanced melanoma. · The 10-year OS rate was 34.0% in the ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01866319

NCT01866319 | Study to Evaluate the Safety and Efficacy ... This study will evaluate the safety and efficacy of 2 different dosing schedules of pembrolizumab (MK-3475), every 2 weeks (Q2W) and every 3 weeks (Q3W),

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4910726/

Clinical activity and safety of Pembrolizumab in Ipilimumab ... 03. Results: Twenty-five patients were identified receiving a median of six cycles of treatment. Two patients achieved a partial response and six patients ...