Blood Test to Guide Immunotherapy for Lung Cancer

Overseen By Juliane A Andrade Czapla, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must be taking: ICI therapy

Must not be taking: Investigational agents, high-dose prednisone

Disqualifiers: Progressive disease, active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a blood test can guide treatment decisions for individuals with certain types of lung cancer or melanoma. It targets patients who have received immune therapy (such as Keytruda) for over a year and have shown stable disease or improvement. Researchers seek to discover if stopping therapy and using a blood test for monitoring can help patients remain disease-free longer. Ideal participants include those with melanoma or non-small-cell lung cancer who have responded well to treatment for at least a year and show no evidence of a specific cancer marker in their blood. As an unphased trial, this study provides patients the chance to contribute to innovative research that may enhance future cancer treatment strategies.

Will I have to stop taking my current medications?

The trial requires participants to continue their current immune checkpoint inhibitor (ICI) therapy, so you will not need to stop taking these medications. However, if you are on more than 10mg of oral prednisone or its equivalent, you may not be eligible to participate.

What prior data suggests that this method is safe for guiding immunotherapy decisions?

Research shows that using circulating tumor DNA (ctDNA) in cancer treatment holds great promise. ctDNA allows doctors to assess treatment effectiveness by detecting small pieces of tumor DNA in the blood.

Studies have shown that ctDNA provides a safe way to monitor patients. It requires only a simple blood test, posing no major risks or side effects. Patients with no detectable ctDNA after certain treatments often experienced better outcomes, indicating that ctDNA can guide decisions on further treatment.

Overall, ctDNA is considered safe and well-tolerated. No reports of harmful effects from the ctDNA test itself exist, making it a safe option in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for lung cancer, which often rely on continuous immunotherapy, this approach uses a blood test to guide active surveillance. Researchers are excited about this trial because it leverages circulating tumor DNA (ctDNA) to monitor patient responses, potentially allowing some patients to pause immunotherapy safely. This method could reduce unnecessary exposure to immune checkpoint inhibitors, minimizing side effects while still keeping a close eye on cancer status through regular blood tests and imaging. Such a personalized and less invasive strategy could revolutionize how lung cancer is managed by tailoring treatment based on real-time molecular changes.

What evidence suggests that using ctDNA to guide therapy decisions is effective for melanoma and non-small-cell lung cancer?

Research has shown that testing for circulating tumor DNA (ctDNA) can help predict outcomes for lung cancer patients. Studies have found that patients without detectable ctDNA after treatment often live longer. For those with non-small cell lung cancer (NSCLC), the absence of ctDNA suggests the disease is under control. Additionally, ctDNA testing can predict cancer recurrence after surgery, providing crucial information about a patient's future health. In this trial, ctDNA testing will guide treatment decisions, such as determining when to stop immune checkpoint inhibitors and begin active surveillance. These findings suggest that ctDNA could help doctors make better treatment decisions for people with metastatic melanoma and NSCLC. ^{1 2 6 7 8}

Who Is on the Research Team?

Meghan J Mooradian, MD

Principal Investigator

Massachusetts General Brigham

Are You a Good Fit for This Trial?

This trial is for adults over 18 with metastatic melanoma or NSCLC who've been on immunotherapy for at least a year and show disease control. They must have had no serious side effects from the therapy, have tumor tissue available for testing, and be expected to live more than 3 months.

Inclusion Criteria

My tumor has been or can be tested with FoundationOne CDx recently.

My cancer has not worsened on scans 12 months after starting immunotherapy.

I have had cancer before, but it doesn't affect my current treatment.

Exclusion Criteria

My condition has worsened in the last 3 months.

I am taking more than 10mg of prednisone daily for immune-related side effects.

I have recovered from side effects of cancer treatment, except for hair loss or hormone issues needing ongoing treatment.

Timeline for a Trial Participant

Pre-screening

Archival tumor tissue is sent to Foundation Medicine for generation of the F1CDx

Not specified

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Active Surveillance

Participants undergo active surveillance with blood draws and standard of care imaging

12 months

Visits at screening, 1 month, 2 months, 3 months, 6 months, 9 months, and 12 months

Follow-up

Participants are monitored for disease-free survival and overall survival

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Evaluation of ctDNA

Trial Overview The study evaluates if measuring ctDNA after one year of immunotherapy can help decide when to stop treatment in patients with melanoma or non-small-cell lung cancer, comparing their disease-free survival against past data.

How Is the Trial Designed?

Group I: Active Surveillance Experimental Treatment 1 Intervention

Patients with 12 month history of immune checkpoint inhibitors (ICI) with stable or partial or complete responses and negative ctDNA at pre-screening, will stop ICI therapy and begin active surveillance with blood draws and standard of care imaging for 12 months.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Foundation Medicine

Industry Sponsor

Trials

37

Recruited

17,600+

Published Research Related to This Trial

Circulating tumor DNA (ctDNA) testing provides a minimally invasive method to diagnose and monitor cancer, reflecting tumor burden and genomic characteristics, which can be crucial for predicting responses to immune checkpoint inhibitor (ICI) therapy.

Sequential ctDNA analyses can identify patients responding to ICI therapy earlier than traditional imaging methods and help differentiate between pseudoprogression and actual disease progression, highlighting its potential as a valuable biomarker in personalized cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and Future Clinical Applications of ctDNA in Immuno-Oncology. Stadler, JC., Belloum, Y., Deitert, B., et al.[2023]

Monitoring circulating tumor DNA (ctDNA) levels can provide an early indication of treatment response in patients with metastatic non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors, with a median time to response of 24.5 days compared to 72.5 days for traditional imaging.

A significant drop in ctDNA levels is associated with improved progression-free survival and overall survival, indicating that ctDNA can be a reliable biomarker for predicting long-term outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA. Goldberg, SB., Narayan, A., Kole, AJ., et al.[2022]

In a study of 92 patients with advanced non-small cell lung cancer (NSCLC), measuring changes in circulating tumor DNA (ctDNA) levels after one cycle of chemotherapy provided early insights into treatment efficacy, with significant associations to patient outcomes.

Patients showing a decrease of 50% or less in ctDNA levels after one cycle had notably lower progression-free survival (33% vs. 58%) and overall survival rates (25% vs. 70%), suggesting that ctDNA monitoring could help identify non-responders early in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Assessment of Chemotherapy Response in Advanced Non-Small Cell Lung Cancer with Circulating Tumor DNA. Yaung, SJ., Woestmann, C., Ju, C., et al.[2023]

In a study of 1,971 patients with advanced non-small-cell lung cancer (NSCLC), 27% had targetable mutations detected through plasma-based ctDNA testing, primarily EGFR-sensitizing mutations.

Patients treated with EGFR-tyrosine kinase inhibitors showed no significant differences in progression-free survival whether their mutations were identified via tissue or plasma testing, indicating that plasma-based profiling is a reliable method for guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes in Non-Small-Cell Lung Cancer Patients Treated With EGFR-Tyrosine Kinase Inhibitors and Other Targeted Therapies Based on Tumor Versus Plasma Genomic Profiling. Tran, HT., Lam, VK., Elamin, YY., et al.[2022]

In a phase II clinical trial involving 94 patients with advanced solid tumors treated with pembrolizumab, baseline levels of circulating tumor DNA (ctDNA) were found to correlate with important outcomes like progression-free survival and overall survival.

Patients who showed clearance of ctDNA during treatment had a promising outcome, with all 12 of these patients remaining alive after a median follow-up of 25 months, suggesting that ctDNA monitoring could be a valuable tool for predicting treatment response in immune checkpoint blockade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Bratman, SV., Yang, SYC., Iafolla, MAJ., et al.[2022]

The BR.36 trial demonstrated that circulating tumor DNA (ctDNA) can effectively indicate primary resistance to immunotherapy in lung cancer, achieving an 82% sensitivity and 75% specificity in predicting radiologic responses to treatment.

Patients who showed a molecular response (mR) through ctDNA clearance had significantly longer progression-free survival (5.03 months) compared to those without mR (2.6 months), highlighting the potential of ctDNA as a biomarker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ctDNA response after pembrolizumab in non-small cell lung cancer: phase 2 adaptive trial results. Anagnostou, V., Ho, C., Nicholas, G., et al.[2023]

Pre-treatment levels of circulating tumor DNA (ctDNA) and peripheral CD8 T cells are strong independent indicators of durable clinical benefit (DCB) in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs).

The study developed a noninvasive assay called DIREct-On, which combines ctDNA and immune cell profiling to accurately predict which patients will achieve DCB, outperforming predictions based on individual factors alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition. Nabet, BY., Esfahani, MS., Moding, EJ., et al.[2021]

In a study of 33 patients with advanced non-small cell lung cancer (NSCLC), ctDNA clearance at 6 weeks post-immunotherapy was linked to decreased tumor volume and significantly longer progression-free survival (PFS) and overall survival (OS).

Patients with positive ctDNA at 6 weeks experienced increased tumor volume and had much shorter PFS and OS, indicating that ctDNA status can serve as a predictive biomarker for the efficacy of sintilimab combined with docetaxel chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term dynamics of circulating tumor DNA predicting efficacy of sintilimab plus docetaxel in second-line treatment of advanced NSCLC: biomarker analysis from a single-arm, phase 2 trial. Han, X., Tang, X., Zhu, H., et al.[2023]

In a study of 42 patients with non-small-cell lung cancer treated with pembrolizumab, higher baseline levels of the proteins Fas ligand (FASLG) and inducible T-cell co-stimulator ligand (ICOSLG) were associated with significantly longer progression-free survival (PFS) and overall survival (OS).

Patients with high expressions of FASLG and ICOSLG who also had no detectable circulating tumor DNA (ctDNA) mutations after treatment initiation experienced even greater improvements in PFS and OS, suggesting these biomarkers could help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma Immune Proteins and Circulating Tumor DNA Predict the Clinical Outcome for Non-Small-Cell Lung Cancer Treated with an Immune Checkpoint Inhibitor. Stensgaard, S., Thomsen, A., Helstrup, S., et al.[2023]

Citations

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Clinical outcomes of a prospective multicenter study ... Clinical outcomes of a prospective multicenter study evaluating a combined circulating tumor DNA (ctDNA) ... non-small cell lung cancer (NSCLC).

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Real-World Validity of Tissue-Agnostic Circulating Tumor ... In patients treated with chemotherapy with or without ICIs, most patients experienced a decrease of 50% in ctDNA regardless of tumor response, whereas only 4/17 ...

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Circulating Tumour DNA (ctDNA) as a Predictor of Clinical ... This systematic review and meta-analysis aimed to evaluate the prognostic value of circulating tumour or cell-free DNA (ctDNA/cfDNA) in NSCLC.

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Predictive Effectiveness of Circulating Tumor DNA in ... In conclusion, ctDNA-MRD testing shows significant potential as a predictive tool for postoperative recurrence in patients with lung cancer.

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Circulating tumor DNA refines consolidation ... Patients with undetectable ctDNA after CCRT had good outcomes with or without consolidation ICI, whereas ctDNA-positive patients at t2, ...

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Analysis of Circulating Tumor DNA Predicts Outcomes ... Detection of ctDNA predicted significantly inferior progression-free survival after completion of CRT (24-mo 29% versus 65%, p = 0.0048), before ...

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Association of circulating tumor DNA (ctDNA) variant allelic ... Our findings highlight that the presence of a detectable targetable driver alt in aNSCLC is actionable, regardless of ctDNA VAF.

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Implementing circulating tumor DNA as a prognostic ... Evaluation of circulating tumor DNA (ctDNA) may meet the need for biomarker-driven optimization of therapeutic allocation in patients with resectable non-small ...