Immune Checkpoint Blockade Therapy Monitoring with PET Scans for Cancer

Overseen By Richard L Wahl, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Checkpoint blockade therapy

Must not be taking: Chemotherapy, Immunosuppressive therapy

Disqualifiers: Other malignancy, Uncontrolled illness, 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

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how PET scans can track the effectiveness of immune checkpoint blockade (ICB) therapy in cancer patients. Researchers aim to determine if changes in tumor activity on these scans can predict who will benefit from the treatment. The trial involves taking PET/CT and PET/MR images before and after the first two cycles of ICB therapy. Suitable participants have confirmed cancer, are scheduled to start ICB therapy, and have a life expectancy between six months and five years. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing valuable insights for participants.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on immunosuppressive therapy, including systemic corticosteroids, unless it's for adrenal insufficiency maintenance. Also, you cannot be on investigational radiotracers within 14 days before imaging or receive ICB with chemotherapy.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that immune checkpoint blockade (ICB) therapy can be safe for cancer patients, though it may cause some side effects. One study found that these side effects are usually not severe and can be managed by doctors.

Patients respond differently to the treatment, with some benefiting more than others. Another study found that even patients with kidney problems did not face higher risks with ICB therapy, suggesting that the therapy is generally well-tolerated across different patient groups.

Overall, ICB therapy has transformed cancer treatment, providing long-lasting benefits to many. While side effects can occur, these studies indicate that the treatment is generally safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how PET scans can enhance immune checkpoint blockade (ICB) therapy for cancer. Unlike traditional imaging methods, this approach combines PET/CT and PET/MR scans to provide detailed insights into how tumors respond to treatment at different stages. This technique could potentially allow for more precise monitoring and adjustment of therapy, helping to tailor treatments to individual patient needs. By offering a real-time glimpse into the effectiveness of ICB therapy, this method aims to improve outcomes and advance personalized cancer care.

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

Research has shown that immune checkpoint blockade (ICB) therapy can help treat various types of cancer. This trial will monitor ICB therapy's effectiveness using PET scans. Studies have found that certain biological indicators, known as biomarkers, can predict which patients will benefit most from this treatment. For instance, a recent study discovered that specific blood tests and clinical information can help forecast a patient's response to the treatment. In one study, pembrolizumab, a type of ICB therapy, had a 43.8% success rate in treating colorectal cancer, surpassing previous treatments. These findings suggest that ICB therapy could be effective for cancer patients, especially when used with accurate prediction tools. ^{4 6 7 8 9}

Who Is on the Research Team?

Richard L Wahl, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with cancer who have a life expectancy of at least 6 months but less than 5 years, and whose disease can be measured. They must be starting immune checkpoint blockade therapy and not be on other investigational drugs or immunosuppressives. Pregnant women, those with certain medical conditions or metal implants incompatible with MRI are excluded.

Inclusion Criteria

Life expectancy ≥ 6 months and < 5 years

Disease that is measurable per RECIST 1.1

Ability and willingness to provide informed consent

Exclusion Criteria

Patient receiving other investigational radiotracers within 14 days prior to FLT and FDG imaging time points

I am receiving immunotherapy combined with chemotherapy.

Pregnant women are excluded from this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment Imaging

Baseline FDG PET/CT imaging as a standard-of-care procedure

1 week

1 visit (in-person)

Treatment Cycle 1

Participants receive immune checkpoint blockade therapy and undergo imaging assessments

4 weeks

1 visit (in-person) for imaging

Treatment Cycle 2

Continued immune checkpoint blockade therapy with follow-up imaging assessments

4 weeks

1 visit (in-person) for imaging

Follow-up

Participants are monitored for response and safety using RECIST 1.1 measurements

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ICB Therapy

Trial Overview

The study tests if PET/CT and PET/MR imaging can predict the success of immune checkpoint blockade therapy in cancer patients by measuring changes in tumor uptake of FLT and FDG after treatment cycles. Responders are expected to show an initial increase followed by a decrease in uptake.

How Is the Trial Designed?

Group I: PET/CT + PET/MR Experimental Treatment 4 Interventions

-Eligible patients will have imaging assessments (as part of the study) performed at three time-points: pre-treatment, following cycle 1 of treatment, and following cycle 2 of treatment. Baseline FDG PET/CT will be a standard-of-care procedure. If possible, PET/CT imaging will be performed, followed immediately by PET/MR imaging during each imaging session. At minimum, PET/MR should be obtained at least once during each time-point (i.e. either during the FDG or FLT procedure). FDG imaging and FLT imaging should be performed at least 24 hours apart and no more than 7 days apart.

ICB Therapy is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Checkpoint Inhibitors for:

• Melanoma
• Non-Small Cell Lung Cancer
• Renal Cell Carcinoma
• Urothelial Carcinoma
• Colorectal Cancer
• Hepatocellular Carcinoma
• Head and Neck Squamous Cell Carcinoma

Approved in United States as Checkpoint Inhibitors for:

• Melanoma
• Non-Small Cell Lung Cancer
• Renal Cell Carcinoma
• Urothelial Carcinoma
• Colorectal Cancer
• Hepatocellular Carcinoma
• Head and Neck Squamous Cell Carcinoma
• Hodgkin Lymphoma

Approved in Canada as Checkpoint Inhibitors for:

• Melanoma
• Non-Small Cell Lung Cancer
• Renal Cell Carcinoma
• Urothelial Carcinoma
• Colorectal Cancer

Approved in Japan as Checkpoint Inhibitors for:

• Melanoma
• Non-Small Cell Lung Cancer
• Renal Cell Carcinoma
• Urothelial Carcinoma

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

Immune checkpoint blockade (ICB) has revolutionized cancer treatment, showing significant effectiveness in metastatic melanoma and expanding to other cancer types and earlier stages.

The review discusses the mechanisms behind varying patient responses to ICB and its integration into both adjuvant (post-surgery) and neoadjuvant (pre-surgery) treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eradicating micrometastases with immune checkpoint blockade: Strike while the iron is hot. Janjigian, YY., Wolchok, JD., Ariyan, CE.[2021]

In a study of 355 patients with metastatic melanoma receiving immune checkpoint blockers, 58.3% developed early immune-related adverse events (irAEs), which were linked to significantly longer progression-free and overall survival rates.

The presence of irAEs was associated with specific gene expression changes in CD8+ T cells, indicating that these adverse events may reflect a baseline level of immune activation that contributes to better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles. Ye, W., Olsson-Brown, A., Watson, RA., et al.[2023]

In a study of 30 patients with metastatic melanoma treated with ipilimumab and pembrolizumab, baseline levels of CD45RO+CD8+ T cells were found to be a significant predictor of response to ipilimumab, with patients having normal levels showing better treatment outcomes.

Patients with low levels of CD45RO+CD8+ T cells did not respond to ipilimumab, suggesting that this biomarker could help identify which patients are more likely to benefit from this specific immune checkpoint blockade therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The proportion of circulating CD45RO+CD8+ memory T cells is correlated with clinical response in melanoma patients treated with ipilimumab. Tietze, JK., Angelova, D., Heppt, MV., et al.[2021]

In a pilot study involving 15 patients with various cancers treated with anti-PD-1 drugs, changes in circulating tumor DNA (ctDNA) levels were significantly correlated with tumor size changes after 8 weeks, indicating ctDNA can effectively monitor treatment response.

Patients whose ctDNA levels became undetectable at 8 weeks showed a strong and lasting response to therapy, and detectable ctDNA at this time was linked to poorer progression-free and overall survival, highlighting its potential as a prognostic marker.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study. Cabel, L., Riva, F., Servois, V., et al.[2022]

A meta-analysis of 113 studies across 25 cancer types revealed a significant correlation between treatment-related adverse events (TrAEs) and the objective response rate (ORR) to immune checkpoint blockade (ICB), suggesting that adverse events could be predictive markers for treatment response.

Specifically, severe TrAEs showed a strong correlation with ORR in melanoma (0.65) and renal cell carcinoma (0.91), indicating that monitoring these adverse events may help identify patients who are more likely to benefit from ICB therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events as surrogate to response rate to immune checkpoint blockade. Shen, Y., Chen, Y., Wang, D., et al.[2021]

High levels of immune checkpoint proteins PD-L1, TIM3, and TIGIT in patients with esophageal squamous cell carcinoma (ESCC) are linked to poorer overall survival, indicating their potential role as prognostic markers.

The combination of PD-L1 with TIM3 or TIGIT is particularly effective in predicting survival outcomes, suggesting these combinations could be targeted in future immunotherapy treatments for ESCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased coexpression of PD-L1 and TIM3/TIGIT is associated with poor overall survival of patients with esophageal squamous cell carcinoma. Wang, P., Chen, Y., Long, Q., et al.[2022]

A study evaluated 22 transcriptome-based biomarkers for immune checkpoint blockade (ICB) therapy response across various cancers, finding that biomarkers like PD-L1, PD-L2, CTLA-4, and CYT significantly correlated with clinical outcomes in melanoma, urothelial cancer, and clear cell renal-cell cancer.

The effectiveness of these biomarkers varied by cancer type and ICB therapy, with PD-L2 and CTLA-4 being particularly predictive in non-small cell lung cancer, highlighting the need for tailored biomarker assessments in ICB treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Assessment of Transcriptomic Biomarkers for Immune Checkpoint Blockade Response in Cancer Immunotherapy. Sun, S., Xu, L., Zhang, X., et al.[2021]

Immune checkpoint blockade (ICB) therapy is effective for treating various tumors by enhancing T-cell activation, but its efficacy is limited in cold tumors due to an immunosuppressive tumor microenvironment.

Recent advances in nano-sized drug delivery systems (Nano-DDS) can enhance ICB therapy by converting cold tumors into immunogenic hot tumors, potentially improving patient responses through the combination of immunogenic cell death inducers and immune modulators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nano-sized drug delivery systems to potentiate the immune checkpoint blockade therapy. Shim, MK., Song, SK., Jeon, SI., et al.[2022]

Immune checkpoint blockers (ICBs) are transforming cancer treatment by targeting various co-inhibitory T-cell receptors, not just the well-known CTLA4 and PD-1, which opens up new possibilities for therapy.

There is a strong focus on identifying biomarkers that can predict which patients will benefit from ICBs, aiming to personalize treatment and minimize severe side effects, which is a key goal in the future of cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial watch: Immune checkpoint blockers for cancer therapy. Vanpouille-Box, C., Lhuillier, C., Bezu, L., et al.[2021]

In a study of 38 metastatic melanoma patients, FDG-PET imaging was found to be more effective than CT imaging in identifying patients with a complete metabolic response (CMR) after discontinuing immune checkpoint blockade (ICB) therapy, with 89.5% showing CMR on PET compared to only 34.2% showing complete response on CT.

Patients with CMR as determined by FDG-PET had a significantly longer time to progression (TTP) compared to those with non-CMR, indicating that FDG-PET can help identify patients at lower risk of relapse and may guide treatment decisions after ICB therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic imaging with FDG-PET and time to progression in patients discontinuing immune-checkpoint inhibition for metastatic melanoma. Ferdinandus, J., Zaremba, A., Zimmer, L., et al.[2022]

In a study of 102 patients treated with immune checkpoint blockade therapy (ICBT) for various solid tumors, 85.3% experienced immune-related adverse events (irAEs), primarily affecting the gastrointestinal, thyroid, and musculoskeletal systems.

Almost half of the patients with irAEs required specific treatment, indicating that while ICBT can be effective, it is associated with a high incidence of adverse effects that may need management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events in patients with solid-organ tumours treated with immunotherapy: a 3-year study of 102 cases from a single centre. Gonzalez-Mazón, I., Sánchez-Bilbao, L., Martín-Varillas, JL., et al.[2022]

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