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

39 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug Keytruda in guiding immunotherapy for lung cancer using a blood test?

Research shows that monitoring changes in circulating tumor DNA (ctDNA) levels can help predict how well patients with lung cancer respond to Keytruda, an immune checkpoint inhibitor. A decrease in ctDNA levels is linked to better survival outcomes, suggesting that ctDNA testing can be an effective way to guide treatment decisions. ^{1 2 3 4 5}

Is the blood test to guide immunotherapy for lung cancer safe for humans?

The studies mention the use of pembrolizumab (Keytruda) and other immune checkpoint inhibitors, which have been used safely in various cancer treatments. While the focus is on effectiveness, these treatments are generally considered safe, with side effects being monitored in clinical settings. ^{1 3 6 7 8}

How does the blood test guide immunotherapy for lung cancer differ from other treatments?

This treatment is unique because it uses a blood test to measure circulating tumor DNA (ctDNA), which helps predict how well a patient will respond to immunotherapy. This approach allows for a more personalized treatment plan by monitoring the tumor's genetic changes over time, potentially leading to better outcomes compared to standard treatments that do not use such biomarkers. ^{1 2 3 7 9}

What is the purpose of this trial?

The goal of this prospective study to investigate the use of circulating tumor DNA (ctDNA) to guide end of therapy decisions in patients with melanoma or non-small-cell lung cancer. The main question it aims to answer is: • Do patients with metastatic melanoma or non-small-cell lung cancer, who have received at least 12 months of immune checkpoint inhibition (monotherapy or in combination) with evidence of disease response/control on imaging and have no evidence of circulating tumor DNA, have an increased 12-month disease free survival in comparison to historical controls?

Research Team

Meghan J Mooradian, MD

Principal Investigator

Massachusetts General Brigham

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. [2022]

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

ctDNA response after pembrolizumab in non-small cell lung cancer: phase 2 adaptive trial results. [2023]

3. England 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. [2023]

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

Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition. [2021]

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

Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA. [2022]

6. Switzerland 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. [2023]

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

Current and Future Clinical Applications of ctDNA in Immuno-Oncology. [2023]

8. United States 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. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Early Assessment of Chemotherapy Response in Advanced Non-Small Cell Lung Cancer with Circulating Tumor DNA. [2023]