Ipilimumab + Pembrolizumab for Brain Metastasis from Melanoma

Overseen By Isabella C Glitza

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune disease, Hepatitis B/C, HIV, 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: 9

Duration: Up to 105 weeks

26 Participants Needed

Trial Summary

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 take corticosteroids or other immunosuppressive medications within 14 days before starting the study, unless they are for physiological replacement.

What data supports the effectiveness of the drug combination Ipilimumab and Pembrolizumab for treating brain metastasis from melanoma?

Research shows that pembrolizumab, one of the drugs in the combination, can lead to rapid and sustained remission of brain metastases in melanoma patients, even without additional radiation therapy. This suggests that pembrolizumab is effective in treating brain metastases, and combining it with ipilimumab may enhance this effect. ^{1 2 3 4 5}

Is the combination of Ipilimumab and Pembrolizumab safe for treating brain metastasis from melanoma?

Pembrolizumab, also known as KEYTRUDA, has been studied for safety in patients with melanoma and brain metastases. Common side effects include issues with the thyroid gland and lung inflammation. These findings suggest that while pembrolizumab is generally safe, it can cause immune-related side effects. ^{1 2 4 6 7}

What makes the drug combination of Ipilimumab and Pembrolizumab unique for treating brain metastasis from melanoma?

This drug combination is unique because it uses two immunotherapy drugs, Ipilimumab and Pembrolizumab, which work by helping the immune system attack cancer cells more effectively. Pembrolizumab has shown promising results in treating brain metastases from melanoma, even in patients who have not received prior treatment for these brain tumors. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase II trial studies the side effects and how well low dose ipilimumab works in combination with pembrolizumab in treating patients with melanoma that has spread to the brain. Immunotherapy with monoclonal antibodies, such as ipilimumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Research Team

Isabella C. Glitza, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for melanoma patients with brain metastases who can follow the study plan, have a measurable brain lesion not previously treated locally, normal blood clotting levels unless on anticoagulants, good organ function, and no severe medical conditions. Pregnant or breastfeeding women and those with certain autoimmune diseases or recent corticosteroid use are excluded.

Inclusion Criteria

My blood clotting tests are within normal limits, or if I'm on blood thinners, they're in the therapeutic range.

I am not breastfeeding and have a recent negative pregnancy test.

Any side effects from my past cancer treatments have mostly gone away.

Exclusion Criteria

I haven't taken high-dose steroids or other immune-weakening drugs in the last 2 weeks.

I have previously received checkpoint inhibitor therapy.

Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive ipilimumab IV over 90 minutes and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 4 cycles for ipilimumab and up to 35 cycles for pembrolizumab in the absence of disease progression or unacceptable toxicity.

Up to 105 weeks

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs at 30 days post-treatment, every 6 weeks for the first year, and then every 12 weeks thereafter.

Up to 1 year

Every 6 weeks for the first year, then every 12 weeks

Treatment Details

Interventions

• Ipilimumab
• Pembrolizumab

Trial Overview The trial tests low dose ipilimumab combined with pembrolizumab in melanoma that has spread to the brain. It aims to see how well these immunotherapy drugs work together by enabling the immune system to target cancer cells more effectively.

Participant Groups

Group I: Treatment (ipilimumab, pembrolizumab) Experimental Treatment 2 Interventions

Patients receive ipilimumab IV over 90 minutes and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 4 cycles for ipilimumab and up to 35 cycles for pembrolizumab in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Pembrolizumab, an anti-PD-1 antibody, has shown a rapid and sustained response in a patient with symptomatic brain metastases from melanoma, achieving complete remission for over a year without the need for additional radiotherapy.

This case suggests that pembrolizumab may be effective for treating brain metastases in melanoma patients, highlighting the importance of conducting further clinical studies to explore its potential in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid remission of symptomatic brain metastases in melanoma by programmed-death-receptor-1 inhibition. Lüttmann, N., Grätz, V., Haase, O., et al.[2018]

In a phase 2 trial involving 36 patients with untreated brain metastases from melanoma or non-small-cell lung cancer (NSCLC), pembrolizumab demonstrated activity, achieving a brain metastasis response in 22% of melanoma patients and 33% of NSCLC patients, with responses being durable for most.

The treatment had an acceptable safety profile, with serious adverse events occurring in a small percentage of patients, indicating that systemic immunotherapy could be a viable option for those with untreated or progressive brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Goldberg, SB., Gettinger, SN., Mahajan, A., et al.[2022]

In a phase II clinical trial involving 23 melanoma patients with untreated brain metastases, pembrolizumab demonstrated a 26% response rate in brain metastases, indicating its potential efficacy in this challenging patient population.

The treatment was associated with acceptable toxicity, as 65% of patients experienced neurologic adverse events, mostly mild (grade 1 or 2), and nearly half of the patients (48%) were alive at 24 months, suggesting durable responses and a need for careful management of brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. Kluger, HM., Chiang, V., Mahajan, A., et al.[2020]

In a phase 2 trial involving 42 patients with untreated brain metastases from non-small-cell lung cancer (NSCLC), pembrolizumab showed a 29.7% response rate in patients with PD-L1 expression of at least 1%, indicating its efficacy in treating brain metastases.

The treatment was generally safe, with serious adverse events occurring in 14% of patients, but no treatment-related deaths were reported, suggesting that pembrolizumab can be a viable option for selected patients with CNS involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. Goldberg, SB., Schalper, KA., Gettinger, SN., et al.[2021]

In a study of 21 melanoma patients with brain metastases treated with concurrent pembrolizumab and radiation therapy, the treatment was found to be safe, with no severe toxicities reported, although one patient experienced Grade 3 side effects.

The use of stereotactic radiosurgery (SRS) alongside pembrolizumab resulted in a high response rate, with 70% of patients showing complete or partial responses at the first follow-up MRI, which is significantly better than response rates seen with SRS combined with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melanoma brain metastases treated with stereotactic radiosurgery and concurrent pembrolizumab display marked regression; efficacy and safety of combined treatment. Anderson, ES., Postow, MA., Wolchok, JD., et al.[2022]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Rapid remission of symptomatic brain metastases in melanoma by programmed-death-receptor-1 inhibition. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Melanoma brain metastases treated with stereotactic radiosurgery and concurrent pembrolizumab display marked regression; efficacy and safety of combined treatment. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]