ctDNA Assay for Lung Cancer

(DNA-PREDICT Trial)

Overseen By Richa Dawar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Miami

Must not be taking: Immunosuppressive drugs

Disqualifiers: Metastatic disease, EGFR mutations, ALK translocation, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that participants should not have had previous exposure to anti-cancer therapy or immunosuppressive drugs within 3 weeks before starting the trial treatment.

What data supports the effectiveness of the drug pembrolizumab for lung cancer?

Research shows that pembrolizumab, when used for non-small-cell lung cancer, can lead to longer survival times, especially in patients with certain biomarkers in their blood. Patients with high levels of specific proteins and no detectable tumor DNA mutations after starting treatment had significantly better outcomes. ^{1 2 3 4 5}

Is pembrolizumab safe for humans?

Pembrolizumab, used in various cancer treatments, has been studied in many trials and is generally considered safe for humans, though individual responses can vary. It is important to discuss potential side effects and safety with a healthcare provider. ^{1 2 4 6 7}

What makes the ctDNA assay with pembrolizumab and platinum doublet chemotherapy unique for lung cancer treatment?

This treatment is unique because it uses circulating tumor DNA (ctDNA) as a biomarker to predict and monitor the response to pembrolizumab, an immune checkpoint inhibitor, combined with platinum doublet chemotherapy. The ctDNA assay helps identify patients who are more likely to benefit from the treatment, allowing for a more personalized approach to managing lung cancer. ^{1 2 3 4 8}

What is the purpose of this trial?

The purpose of this study is to determine if a blood test called circulating tumor DNA (ctDNA) can be used to predict how well patients will respond to treatment and if there is any cancer left after surgery. The investigators will also study if a drug called pembrolizumab can help prevent the cancer from coming back in patients who are ctDNA-positive or who have evidence of cancer after treatment and surgery.

Research Team

Richa Dawar, MD

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for individuals with non-small cell lung cancer. Participants must be suitable for chemotherapy and surgery, and willing to undergo blood tests to measure ctDNA levels. Specific eligibility criteria are not provided but typically include factors like age, overall health, and cancer stage.

Inclusion Criteria

I am fully active or have some restrictions but can still care for myself.

Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

My lung cancer is at a specific stage and I am set to receive treatment before surgery.

Exclusion Criteria

I am unable to make my own medical decisions.

My cancer has EGFR mutations or ALK translocation.

My cancer has spread and cannot be removed by surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant treatment including ctDNA monitoring, SOC Pembrolizumab, and SOC platinum doublet chemotherapy

3 months

Regular visits for treatment and monitoring

Surgery

Participants undergo surgery for resection of the tumor

1 week

1 visit (in-person)

Adjuvant Treatment

Participants receive adjuvant treatment with Pembrolizumab and ctDNA monitoring to prevent cancer recurrence

Up to 1.5 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for recurrence-free survival and overall survival

Up to 2.5 years

Periodic follow-up visits

Treatment Details

Interventions

• Pembrolizumab
• Platinum Doublet Chemotherapy

Trial Overview The study aims to see if a blood test (ctDNA assay) can predict treatment response in non-small cell lung cancer patients receiving pembrolizumab and platinum doublet chemotherapy. It also examines the use of pembrolizumab in preventing cancer recurrence post-surgery in ctDNA-positive patients.

Participant Groups

Group I: ctDNA Monitoring Group Experimental Treatment 3 Interventions

Participants in this group will receive ctDNA monitoring in combination with standard of care (SOC) Pembrolizumab, SOC platinum doublet chemotherapy, and SOC surgery for resection of tumor. Total participation duration is up to 2.5 years.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

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]

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]

In a study of 73 patients with advanced solid tumors receiving pembrolizumab, ctDNA monitoring was shown to correlate with treatment outcomes, indicating that changes in ctDNA levels can help predict patient survival and clinical benefit from immune checkpoint blockade.

High mutation burden and specific immune signatures were linked to better responses to pembrolizumab, while certain genetic alterations, like B2M loss-of-heterozygosity, were associated with treatment resistance, highlighting the complex relationship between tumor genetics and immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity. Cindy Yang, SY., Lien, SC., Wang, BX., et al.[2022]

In a study of 145 patients with PD-L1 strongly positive non-small-cell lung cancer (NSCLC), those with higher PD-L1 expression (≥ 75%) experienced better treatment outcomes with pembrolizumab, showing a higher objective response rate (51% vs. 33%) and longer progression-free survival (13.9 months vs. 5.2 months).

Patients with liver metastasis had significantly poorer responses to pembrolizumab, with an objective response rate of only 20% compared to 47% in those without liver metastasis, indicating that both PD-L1 expression and liver metastasis are important predictors of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC. Takeyasu, Y., Yoshida, T., Shibaki, R., et al.[2021]

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]

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. 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]

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

Early plasma circulating tumor DNA (ctDNA) changes predict response to first-line pembrolizumab-based therapy in non-small cell lung cancer (NSCLC). [2023]

4. China pubmed.ncbi.nlm.nih.gov

Blood tumor mutational burden and dynamic changes in circulating tumor DNA predict response to pembrolizumab treatment in advanced non-small cell lung cancer. [2023]

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

Clinical potential of circulating free DNA and circulating tumour cells in patients with metastatic non-small-cell lung cancer treated with pembrolizumab. [2022]

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

Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity. [2022]

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

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC. [2021]

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

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