Checkpoint Inhibitor Therapy Response Assessment for Cancer

Recruiting at 1 trial location

Overseen By LIbby Mirande

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CellSight Technologies, Inc.

Disqualifiers: Pregnancy, Breastfeeding

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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3-6 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a cancer treatment called Checkpoint Inhibitor Therapy. Researchers will use a special scan, \[18F\]F AraG PET/CT imaging, to observe the treatment's impact on solid tumors. The goal is to determine if this scan can detect changes in tumors after treatment. Individuals with advanced solid tumors, who are scheduled to receive this therapy and have at least two tumors suitable for scanning, might qualify for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that checkpoint inhibitor therapy is usually well-tolerated. These drugs enhance the immune system's ability to attack cancer cells. Studies have found that patients often manage this treatment well, even with other health issues like kidney problems.

However, side effects can occur. Some individuals might experience immune-related issues, where the immune system attacks healthy parts of the body, not just the cancer. These side effects can vary, and doctors have methods to manage them.

Overall, checkpoint inhibitors represent a breakthrough in cancer treatment, offering hope to many patients. However, like any treatment, they come with risks that require careful monitoring. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Checkpoint inhibitor therapy is unique because it helps the immune system recognize and attack cancer cells, unlike traditional treatments like chemotherapy and radiation that directly target cancer cells. This therapy focuses on blocking certain proteins that prevent immune cells from attacking tumors, essentially "taking the brakes off" the immune system. Researchers are excited about checkpoint inhibitors because they have shown promise in treating various types of cancer with fewer side effects and the potential for long-lasting responses compared to conventional therapies.

What evidence suggests that Checkpoint Inhibitor Therapy could be effective for cancer?

Research shows that checkpoint inhibitor therapy has greatly improved outcomes for cancer patients. This treatment helps the immune system find and attack cancer cells more effectively. Studies have found that combining these therapies can lead to promising results, especially for colorectal cancer. This combination also reduces the number of tired immune cells, potentially leading to better cancer control. Overall, checkpoint inhibitors have provided lasting benefits and represent a major advancement in cancer treatment. ^{3 6 7 8 9}

Who Is on the Research Team?

Shivaani Kummar, MD

Principal Investigator

Oregon Health and Science University

Erik Mittra, M.D.

Principal Investigator

Oregon Health and Science University

Carina Mari Aparici

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced solid tumors who are planning to receive checkpoint inhibitor therapy (CkIT). They must have at least two qualifying lesions and provide signed informed consent. Pregnant or breastfeeding individuals cannot participate.

Inclusion Criteria

I am over 18 years old.

My solid tumor is planned for a CkIT test.

Signed Informed Consent Form

Exclusion Criteria

Patient is pregnant or breast feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Imaging

Pre-therapy [18F]F AraG PET/CT scan administered within 14 days prior to initial CkIT administration

2 weeks

1 visit (in-person)

Treatment

Patients receive Checkpoint Inhibitor Therapy (CkIT) and undergo biopsy of one lesion

3-6 weeks

1 visit (in-person)

Post-Treatment Imaging

Post-therapy [18F]F AraG PET/CT scan performed 3 to 6 weeks after initial CkIT dose

3-6 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Checkpoint Inhibitor Therapy

Trial Overview The study is testing the use of a special PET/CT imaging technique using [18F]F AraG to see how well patients with solid tumors respond to CkIT, which is a type of cancer treatment that helps the immune system fight cancer.

Checkpoint Inhibitor Therapy is already approved in United States, China, European Union for the following indications:

Approved in United States as Checkpoint Inhibitors for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck cancer
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Small cell lung cancer
• Esophageal carcinoma
• Malignant pleural mesothelioma
• Gastric cancer
• Cervical cancer
• Endometrial cancer
• Squamous cell carcinoma
• Biliary tract cancer

Approved in China as Checkpoint Inhibitors for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck cancer
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Small cell lung cancer
• Esophageal carcinoma
• Malignant pleural mesothelioma
• Gastric cancer
• Cervical cancer

Approved in European Union as Checkpoint Inhibitors for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck cancer
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Small cell lung cancer
• Esophageal carcinoma
• Malignant pleural mesothelioma
• Gastric cancer
• Cervical cancer

Who Is Running the Clinical Trial?

CellSight Technologies, Inc.

Lead Sponsor

Trials

18

Recruited

320+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

A 63-year-old man with metastatic melanoma showed a successful response to combination therapy with CTLA-4 and PD-1 inhibitors (ipilimumab and nivolumab) after initially not responding to pembrolizumab, highlighting the potential effectiveness of this combination treatment.

Increased FDG uptake in benign lymphoid tissue observed on PET/CT scans may indicate immune activation rather than disease progression, suggesting it could serve as a useful biomarker for assessing treatment response in patients undergoing immune checkpoint blockade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased FDG avidity in lymphoid tissue associated with response to combined immune checkpoint blockade. Tsai, KK., Pampaloni, MH., Hope, C., et al.[2018]

Immunotherapy, particularly using checkpoint inhibitors like PD-1 and PD-L1, has shown significant survival benefits in certain cancer patients, including those with melanoma and lung cancer.

Despite their effectiveness, many patients do not respond to these costly treatments, highlighting the urgent need for reliable biomarkers to predict which patients will benefit from PD-1/PD-L1 inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers of response to PD-1/PD-L1 inhibition. Maleki Vareki, S., Garrigós, C., Duran, I.[2022]

Immune checkpoint inhibitors (ICIs) can lead to unique response patterns in patients, such as durable responses and pseudoprogression, which can affect prognosis and treatment decisions.

Current response evaluation criteria (RECIST) are often modified for ICIs, but the standard RECIST1.1 is still the most widely used in clinical trials, highlighting the need for further research to optimize treatment strategies beyond progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Response Evaluation and Treatment with Immune Checkpoint Inhibitors Beyond Clinical Progression: Response Assessments for Cancer Immunotherapy. Mushti, SL., Mulkey, F., Tang, S., et al.[2021]

Immunotherapy using immune checkpoint inhibitors targeting CTLA-4 and PD-1/PD-L1 has shown promising efficacy in treating melanoma, enhancing T cell responses to fight tumors.

Despite the success of these therapies, reliable predictors of which patients will benefit from immunotherapy are still being researched, highlighting the need for ongoing efforts to identify effective predictive markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive factors for immunotherapy in melanoma. Teixidó, C., González-Cao, M., Karachaliou, N., et al.[2022]

Ipilimumab, an anti-CTLA-4 antibody, and nivolumab/pembrolizumab, anti-PD-1 antibodies, are FDA-approved treatments that enhance the immune system's ability to fight various cancers, particularly melanoma.

While these immune checkpoint inhibitors are effective, they can cause immune-related adverse events (irAEs) affecting multiple organ systems, which can be managed with temporary immunosuppression using corticosteroids and other agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing immune checkpoint-blocking antibody side effects. Postow, MA.[2022]

Inhibition of immune checkpoints using PD-1 and CTLA-4 monoclonal antibodies has significantly improved treatment options for advanced-stage melanoma and other cancers, with FDA approval for their use in metastatic melanoma.

While these immunotherapies are effective, they can cause a range of immune-related adverse events, particularly affecting the skin, gastrointestinal tract, liver, and endocrine systems, necessitating careful management of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Boutros, C., Tarhini, A., Routier, E., et al.[2022]

In a study of 222 metastatic melanoma patients, higher serum levels of PD-1 and PD-L1 were found to be associated with poorer responses to anti-PD-1 therapy, indicating these markers could help predict treatment outcomes.

The combination of PD-1 and PD-L1 serum levels was shown to effectively distinguish between favorable and poor outcomes in patients receiving PD-1 inhibitors, making them valuable biomarkers for guiding treatment decisions between PD-1 and BRAF therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elevated baseline serum PD-1 or PD-L1 predicts poor outcome of PD-1 inhibition therapy in metastatic melanoma. Ugurel, S., Schadendorf, D., Horny, K., et al.[2022]

A retrospective review of adverse events reported to the FDA revealed that PD-1 and PD-L1 inhibitors are associated with an increased risk of tuberculosis (TB) and atypical mycobacterial infection (AMI), with 72 cases of TB and 13 cases of AMI identified among users of these drugs.

The risk of developing TB was found to be 1.79 times higher and the risk of AMI was 5.49 times higher in patients treated with PD-1/PD-L1 inhibitors compared to other FDA-approved drugs, indicating that while these therapies can be effective for cancer, they carry significant risks that clinicians should monitor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycobacterial infections due to PD-1 and PD-L1 checkpoint inhibitors. Anand, K., Sahu, G., Burns, E., et al.[2021]

In a study of 99 patients with metastatic melanoma treated with immunotherapy, those who experienced immune-related adverse events (irAEs) had a significantly better overall response rate (57%) and longer progression-free survival (301.6 days) compared to those without irAEs (37% response rate and 247.29 days).

The survival probability for patients with irAEs increased dramatically from less than 60% to almost 80%, suggesting that the occurrence of these adverse events may be associated with improved treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events during immunotherapy in Slovenian patients with metastatic melanoma reveal a positive correlation with better treatment outcomes. Mesti, T., Ceplak Mencin, V., Mileva Boshkoska, B., et al.[2023]

In a study of 52 hospitalized cancer patients treated with immune checkpoint inhibitors, 68.2% either died or were admitted to hospice within 90 days, indicating a high rate of poor outcomes in this population.

Patients who had not previously received immune checkpoint inhibitors before hospitalization had a significantly shorter time to death or hospice (29 days) compared to those who had prior treatment (242 days), suggesting that prior exposure to these therapies may influence survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inpatient utilization of immune checkpoint inhibitors and clinical outcomes. Wang, J., Lee, CS., Attarian, S., et al.[2023]

Two lung cancer patients treated with the checkpoint inhibitor nivolumab developed significant pleural and pericardial effusions shortly after starting therapy, highlighting the need for careful monitoring in patients with a history of malignant spread to these areas.

Despite the complications, one patient experienced a near complete response to treatment after 16 weeks, suggesting that effusions may represent pseudoprogression, and that continuing therapy with close monitoring can be beneficial if the effusions are manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent pleural effusions and cardiac tamponade as possible manifestations of pseudoprogression associated with nivolumab therapy- a report of two cases. Kolla, BC., Patel, MR.[2022]

The study developed a framework using real-world data from the FDA's Adverse Event Reporting System to detect and filter immune-related adverse events (irAEs) associated with six FDA-approved immune checkpoint inhibitors, identifying 94 positive signals.

Out of these signals, 31 (33%) were classified as potentially new irAEs, highlighting the framework's effectiveness in discovering novel safety concerns that may not be documented in existing drug labels or literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detecting and Filtering Immune-Related Adverse Events Signal Based on Text Mining and Observational Health Data Sciences and Informatics Common Data Model: Framework Development Study. Yu, Y., Ruddy, K., Mansfield, A., et al.[2020]

Immune checkpoint inhibitors like anti-PD-1, anti-PD-L1, and anti-CTLA-4 have revolutionized cancer treatment, but their effectiveness varies, with response rates between 10% and 30%.

Current efforts are focused on identifying new biomarkers, such as INF-γ and mutational load, to better predict which patients will benefit from these therapies, as existing methods like PD-L1 status are not sufficient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immune checkpoints inhibitors: Recent data from ASCO's meeting 2017 and perspectives]. Kfoury, M., Disdero, V., Vicier, C., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8556173/

Inhibitors of immune checkpoints—PD-1, PD-L1, CTLA-4— ... The purpose of this article is an attempt to familiarize internists and GPs with the possible complications arising from the use of immune checkpoint inhibitors ...

2. nature.com nature.com/articles/s41591-024-03398-5

Prediction of checkpoint inhibitor immunotherapy efficacy ... In this study, we explored whether a machine learning system could predict ICI outcomes using routine blood tests and standard clinical variables.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0092867423002246

Review Immune checkpoint therapy—current perspectives ... Immune checkpoint therapy (ICT) has dramatically altered clinical outcomes for cancer patients and conferred durable clinical benefits, ...

4. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1485303/full

Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune ... Conclusion: PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors have shown promising clinical responses in the treatment of colorectal cancer (CRC). Although ...

5. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01581-2

Dual blockade immunotherapy targeting PD-1/PD-L1 and ... The combined use of dual immune checkpoint inhibitors significantly decreased the proportion of exhausted phenotype cytotoxic CD8+ T-cells, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5388381/

Safety and Tolerability of PD‐1/PD‐L1 Inhibitors Compared ... The development of immune checkpoint inhibitors (ICIs) represents a major breakthrough in cancer therapy. ICIs enhance antitumor immune responses by releasing ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.01440

Management of Immune-Related Adverse Events in ... Checkpoint inhibitor therapy appears to be safe in patients with baseline renal impairment from a nonimmune basis (eg, prior nephrectomy, old age, and ...

8. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/2830216

Immune Checkpoint Inhibitors in Field Cancerization and ... This pilot cohort study found that ICIs used for any cancer were associated with a significant reduction of AKs, suggesting potential as an immunopreventive ...

9. nature.com nature.com/articles/s41571-019-0218-0

Adverse effects of immune-checkpoint inhibitors However, both immune checkpoints can also be hijacked by cancer cells in order to develop a microenvironment that is tolerant of tumour growth.