Immune Checkpoint Blockade Therapy Monitoring with PET Scans for Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Richard L Wahl, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Washington University School of Medicine

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

In the current study, advanced positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance (PET/MR) imaging methods will be used to validate the hypothesis that participants receiving immune checkpoint blockade (ICB) therapy, who ultimately achieve clinical benefit, will show an increase, or "FLARE", in tumor FLT and/or FDG uptake from baseline, as seen after cycle#1 of treatment, and that after 2 cycles of treatment responders will have a decline in FLT and FDG uptake, in comparison to the participants classified as "non-responders".

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.

What data supports the idea that Immune Checkpoint Blockade Therapy Monitoring with PET Scans for Cancer is an effective treatment?

The available research shows that Immune Checkpoint Blockade (ICB) therapy has been effective in treating certain types of cancer, such as metastatic melanoma, with about 20-40% of patients experiencing long-term benefits. Additionally, ICB therapy has been approved for various tumor types and has led to complete tumor regression in some patients. However, the response rate is limited, and not all patients benefit equally from this treatment. Despite these challenges, ICB therapy has significantly improved outcomes for patients with solid tumors compared to other treatments. ^{1 2 3 4 5}

What safety data exists for immune checkpoint blockade therapy?

Immune checkpoint blockade therapy (ICB) can lead to immune-related adverse events (irAEs) as it activates CD8+ T cells, which are associated with both anti-cancer activity and potential autoimmunity. Studies have shown that these irAEs can be linked to favorable outcomes in some cases, such as metastatic melanoma. Efforts are ongoing to identify biomarkers that predict clinical benefits and minimize severe toxicity, aiming to tailor ICB therapy to individual patients. A study from Northern Spain assessed irAEs in patients with solid-organ tumors treated with ICB, highlighting the need for careful monitoring of these adverse events. ^{6 7 8 9 10}

Is the treatment Immune Checkpoint Blockade Therapy a promising treatment for cancer?

Yes, Immune Checkpoint Blockade Therapy is a promising treatment for cancer. It has shown success in treating advanced cancers like melanoma and is being used for other types and stages of cancer. It offers hope to many patients by potentially eradicating small, hard-to-detect cancer cells and improving long-term outcomes. ^{1 2 9 10 11}

Research Team

Richard L Wahl, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

Disease that is measurable per RECIST 1.1

Women of child-bearing potential must have a negative urinary or serum pregnancy test within 7 days of each imaging time point

My doctor plans for me to receive immunotherapy.

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

Treatment Details

Interventions

• ICB Therapy (Checkpoint Inhibitor)

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.

Participant Groups

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 Canada, Japan for the following indications:

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Washington University School of Medicine Saint Louis, MO

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

Findings from Research

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]

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]

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]

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]

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 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]

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 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]

References

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

Treatment-related adverse events as surrogate to response rate to immune checkpoint blockade. [2021]

2. England 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. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Assessment of Transcriptomic Biomarkers for Immune Checkpoint Blockade Response in Cancer Immunotherapy. [2021]

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

Nano-sized drug delivery systems to potentiate the immune checkpoint blockade therapy. [2022]

5. England 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles. [2023]

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

Trial watch: Immune checkpoint blockers for cancer therapy. [2021]

8. Italy 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. [2022]

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

Eradicating micrometastases with immune checkpoint blockade: Strike while the iron is hot. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Metabolic imaging with FDG-PET and time to progression in patients discontinuing immune-checkpoint inhibition for metastatic melanoma. [2022]