Biomarker-Guided Immunotherapy Discontinuation for Melanoma

Recruiting in Palo Alto (17 mi)

+456 other locations

Overseen by Geoffrey T Gibney

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: ECOG-ACRIN Cancer Research Group

Must be taking: Anti-PD-1 therapy

Must not be taking: Anticoagulation therapy

Disqualifiers: Brain metastases, Pregnancy, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial uses drugs that boost the immune system to fight advanced melanoma that can't be surgically removed. It aims to see if doctors can safely shorten the treatment period by using imaging tests to guide decisions. Pembrolizumab and ipilimumab are immunotherapy drugs used to treat advanced melanoma, with pembrolizumab approved for younger patients and ipilimumab showing positive results in previous studies.

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

The trial does not specify if you need to stop taking your current medications, but you must not be on other anti-tumor therapies besides the standard anti-PD-1 regimens. If you are on anticoagulation therapy, you may need to pause it for a biopsy procedure.

What data supports the effectiveness of this drug for melanoma?

Research shows that pembrolizumab works better than ipilimumab for treating advanced melanoma, and nivolumab has shown long-term survival benefits. These drugs, along with others like ipilimumab and nivolumab/ipilimumab combinations, have improved outcomes for melanoma patients, although there are differences in how long patients stay on these treatments. ^{1 2 3 4 5}

What safety data exists for pembrolizumab and other similar treatments in humans?

Pembrolizumab (Keytruda) and similar treatments like ipilimumab (Yervoy) and nivolumab (Opdivo) have been generally well-tolerated in clinical trials for melanoma, with common side effects including fatigue, rash, itching, and diarrhea. Some less common but serious immune-related side effects include inflammation of the lungs (pneumonitis), liver (hepatitis), and intestines (colitis), as well as thyroid problems. ^{6 7 8 9 10}

How is the drug Nivolumab or Pembrolizumab unique for treating melanoma?

Nivolumab and Pembrolizumab are unique for treating melanoma because they are immune checkpoint inhibitors that help the immune system recognize and attack cancer cells. Pembrolizumab has shown better outcomes compared to ipilimumab and can lead to durable complete remission even after discontinuation, offering hope for long-term survival. ^{1 2 4 5 11}

Research Team

Geoffrey T Gibney

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults with unresectable stage IIIB-IV melanoma. Participants must have had a positive response to initial anti-PD-1 therapy, meet specific health criteria (like normal organ function tests), and not be pregnant or breastfeeding. They should not have brain metastases or other conditions that could affect the study's safety or results.

Inclusion Criteria

Your platelet count is at least 100,000 per microliter, as measured within the last 4 weeks before joining the study.

My heart function is classified as class 2B or better, despite my history of heart issues or treatments.

Your total bilirubin level should be within the normal range, unless you have a history of Gilbert's syndrome, in which case it can be slightly higher.

Exclusion Criteria

I am using or willing to use effective birth control during and after the study as required.

I do not have cancer that has spread to my brain.

Women must not be pregnant or breast-feeding due to potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the anti-PD-1 regimens being used. All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard of care anti-PD-1 therapy, including regimens with nivolumab, pembrolizumab, and ipilimumab, for up to 52 weeks

52 weeks

Evaluation and Decision

Participants are evaluated using FDG-PET/CT scans and biopsies to determine continuation or discontinuation of therapy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up through week 97 and then every 3 months for up to 5 years

5 years

Treatment Details

Interventions

• Ipilimumab (CTLA-4 Inhibitor)
• Nivolumab (PD-1 Inhibitor)
• Pembrolizumab (PD-1 Inhibitor)

Trial Overview The PET-Stop Trial is testing if biomarkers from PET/CT imaging can guide when to safely stop immunotherapy in patients with advanced melanoma. It involves drugs like Pembrolizumab, Ipilimumab, Nivolumab, and patient observation to determine the effectiveness of early discontinuation.

Participant Groups

Group I: Standard of Care (nivolumab, pembrolizumab, ipilimumab) Experimental Treatment 3 Interventions

Patients continue their standard of care anti-PD-1 therapy. Treatment may consist of the following regimens: 1) nivolumab IV over 30 minutes Q2W or Q4W; 2) pembrolizumab IV over 30 minutes Q3W or Q6W; 3) nivolumab IV over 30 minutes and ipilimumab IV Q3W for 4 doses followed by nivolumab IV over 30 minutes Q2W or Q4W; or 4) pembrolizumab IV over 30 minutes and ipilimumab IV Q3W for 4 doses followed by pembrolizumab IV over 30 minutes Q3W or Q6W. Treatment continues until 52 weeks from start of standard of care anti-PD-1 therapy in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (active surveillance) Experimental Treatment 1 Intervention

Patients with a negative FDG-PET/CT scan or a positive FDG-PET/CT scan but with a negative biopsy for viable tumor discontinue the anti-PD-1 therapy and undergo active surveillance.

Group III: Arm B (nivolumab, pembrolizumab, ipilimumab) Active Control 2 Interventions

Patients with a positive FDG-PET/CT scan and positive biopsy for viable tumor or a positive FDG-PET/CT scan and biopsy not performed continue their standard of care anti-PD-1 therapy for 12 months in the absence of disease progression or unacceptable toxicity.

Nivolumab is already approved in Canada, Switzerland for the following indications:

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Rocky Mountain Cancer Centers-Boulder Boulder, CO

Saint Joseph Mercy Canton Canton, MI

Saint Francis Cancer Center Colorado Springs, CO

Cedars Sinai Medical Center Los Angeles, CA

More Trial Locations

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Patients Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14080

Patients Recruited

41,180,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic melanoma patient outcomes since introduction of immune checkpoint inhibitors in England between 2014 and 2018. Board, R., Smittenaar, R., Lawton, S., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab superior to ipilimumab in melanoma. [2017]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Meng, Y., Hertel, N., Ellis, J., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes by line of therapy and programmed death ligand 1 expression in patients with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE-006: A randomised clinical trial. Carlino, MS., Long, GV., Schadendorf, D., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world analyses of therapy discontinuation of checkpoint inhibitors in metastatic melanoma patients. Machado, MAÁ., de Moura, CS., Chan, K., et al.[2021]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of immune-checkpoint inhibitors and the risk of immune-related colitis among elderly patients with advanced melanoma: real-world evidence from the SEER-Medicare database. Almutairi, AR., Slack, M., Erstad, BL., 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]

In a meta-analysis of 15 studies involving cancer patients treated with either nivolumab or pembrolizumab, nivolumab was associated with a higher overall incidence of cardiotoxicity (55.7%) compared to pembrolizumab (27.31%), although this difference was not statistically significant.

However, when looking specifically at myocarditis, pembrolizumab showed a significant increase in cardiotoxicity risk, suggesting that while nivolumab may be more commonly reported for general cardiotoxicity, pembrolizumab poses a greater risk for this specific heart condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. Ndjana Lessomo, FY., Wang, Z., Mukuka, C.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma. Robert, C., Ribas, A., Hamid, O., et al.[2022]

References

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

Metastatic melanoma patient outcomes since introduction of immune checkpoint inhibitors in England between 2014 and 2018. [2021]

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

Pembrolizumab superior to ipilimumab in melanoma. [2017]

3. Germany pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. [2020]

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

Outcomes by line of therapy and programmed death ligand 1 expression in patients with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE-006: A randomised clinical trial. [2022]

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

Real-world analyses of therapy discontinuation of checkpoint inhibitors in metastatic melanoma patients. [2021]

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 in the management of metastatic melanoma. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Association of immune-checkpoint inhibitors and the risk of immune-related colitis among elderly patients with advanced melanoma: real-world evidence from the SEER-Medicare database. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. [2023]

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

Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma. [2022]