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

Trial Summary

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.

What data supports the effectiveness of the treatment Checkpoint Inhibitor Therapy for cancer?

Research shows that immune checkpoint inhibitors, which target proteins like PD-1 and CTLA-4, have shown promising results in treating melanoma and other cancers by boosting the body's immune response against tumors. However, the response rate varies, and ongoing studies are trying to identify which patients will benefit the most from this treatment. ^{1 2 3 4 5}

What safety information is available for checkpoint inhibitor therapy?

Checkpoint inhibitor therapy, including drugs like CTLA-4 and PD-1 inhibitors, is generally safe but can cause immune-related side effects. These side effects may affect the skin, stomach, liver, and hormone systems, and include issues like rash, nausea, and thyroid problems. Temporary treatments with medications like corticosteroids can help manage these side effects. ^{6 7 8 9 10}

How is Checkpoint Inhibitor Therapy different from other cancer treatments?

Checkpoint Inhibitor Therapy is unique because it uses the body's own immune system to fight cancer by blocking proteins that stop immune cells from attacking cancer cells. This approach, targeting proteins like CTLA-4 and PD-1, is different from traditional treatments like chemotherapy, which directly kill cancer cells. ^{1 5 11 12 13}

What is the purpose of this trial?

In this study, patients with advanced solid tumors will undergo \[18F\]F AraG PET/CT imaging to assess for changes in tracer uptake following treatment with CkIT.

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

Eligibility Criteria

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

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

Treatment Details

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+

Findings from Research

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]

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]

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]

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 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]

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]

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 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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

Predictive factors for immunotherapy in melanoma. [2022]

2. France pubmed.ncbi.nlm.nih.gov

[Immune checkpoints inhibitors: Recent data from ASCO's meeting 2017 and perspectives]. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Inpatient utilization of immune checkpoint inhibitors and clinical outcomes. [2023]

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

Elevated baseline serum PD-1 or PD-L1 predicts poor outcome of PD-1 inhibition therapy in metastatic melanoma. [2022]

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

Increased FDG avidity in lymphoid tissue associated with response to combined immune checkpoint blockade. [2018]

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

Mycobacterial infections due to PD-1 and PD-L1 checkpoint inhibitors. [2021]

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

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

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

Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. [2022]

9. Poland pubmed.ncbi.nlm.nih.gov

Adverse events during immunotherapy in Slovenian patients with metastatic melanoma reveal a positive correlation with better treatment outcomes. [2023]

10. Canada 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. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Biomarkers of response to PD-1/PD-L1 inhibition. [2022]

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

Immune Response Evaluation and Treatment with Immune Checkpoint Inhibitors Beyond Clinical Progression: Response Assessments for Cancer Immunotherapy. [2021]

13. England 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. [2022]