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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a special blood test, called ctDNA, can predict lung cancer patients' response to treatment and detect cancer presence after surgery. The study also examines if the drug pembrolizumab (an immunotherapy) can help prevent cancer recurrence in patients who test positive for ctDNA or show signs of cancer post-treatment. Participants will receive standard treatments, including chemotherapy and surgery, along with pembrolizumab. Suitable candidates for this trial include those diagnosed with certain stages of non-small cell lung cancer who plan to undergo surgery after initial treatments like chemotherapy and immunotherapy. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants the chance to contribute to significant findings in lung cancer treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pembrolizumab, a medication in this trial, has been studied for safety over several years. In past studies, pembrolizumab, either alone or with chemotherapy, showed promising results for people with non-small cell lung cancer (NSCLC). For instance, when combined with chemotherapy, about 19% of patients lived for five years after treatment. This indicates that nearly 1 in 5 patients survived for five years, highlighting the medication's effectiveness and safety.

Regarding side effects, studies have found some, like tiredness, nausea, and skin reactions, but they were generally manageable. This suggests that pembrolizumab is usually well-tolerated.

Platinum doublet chemotherapy, another part of the trial, is a common lung cancer treatment. Research indicates it can be effective, but it also has side effects like low blood cell counts, nausea, and hair loss. These are known, and doctors are skilled at managing them.

While the trial is in its early stages, previous data on these treatments suggest they are safe. Always consult a doctor to determine if this trial is a suitable option. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it uses ctDNA monitoring, a cutting-edge technique to track how lung cancer patients respond to treatments like Pembrolizumab and platinum doublet chemotherapy. This approach is unique because it allows doctors to detect tumor DNA in the blood, potentially catching any changes in the cancer's behavior much earlier than traditional scans. By integrating this real-time monitoring with standard treatments, there's hope for more personalized and effective care, potentially improving outcomes for patients with lung cancer.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research shows that pembrolizumab holds promise for treating non-small cell lung cancer (NSCLC). In this trial, participants in the ctDNA Monitoring Group will receive pembrolizumab as part of their treatment. Studies have found that changes in ctDNA—small pieces of cancer DNA in the blood—after pembrolizumab treatment link to better outcomes. A drop in ctDNA levels during treatment may indicate a positive cancer response. Additionally, participants will receive platinum doublet chemotherapy, which combines two chemotherapy drugs, as part of the standard lung cancer treatment. These treatments work together to reduce cancer and improve survival chances by targeting cancer cells more effectively. ^{6 7 8 9 10}

Who Is on the Research Team?

Richa Dawar, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. nature.com nature.com/articles/s41591-023-02598-9

ctDNA response after pembrolizumab in non-small cell ... BR.36 is a multi-center, randomized, ctDNA-directed, phase 2 trial of molecular response-adaptive immuno-chemotherapy for patients with lung cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12261352/

Monitoring pembrolizumab response in NSCLC with ctDNA/ctc Early treatment circulating tumour DNA (ctDNA) dynamics correlates with improved clinical outcomes in advanced non-small cell lung cancer (NSCLC) ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2547

Personalized tumor-informed circulating tumor DNA as ... Dynamic monitoring circulating tumor DNA in plasma samples by PEAC technology for patients with early-stage non–small cell lung cancer after ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666364325000451

Real-World Validity of Tissue-Agnostic Circulating Tumor ... Here, we report the real-world clinical validity of tissue-agnostic ctDNA monitoring for prognosticating whether patients with lung cancer will have favorable ...

5. oncology.labcorp.com oncology.labcorp.com/ctdna-response-after-pembrolizumab-non-small-cell-lung-cancer-phase-2-adaptive-trial-results

ctDNA response after pembrolizumab in non-small cell ... Results from the first stage of the Phase 2 BR.36 trial found high concordance between ctDNA response and radiographic response among 50 advanced lung cancer ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39952082/

Five-year efficacy and safety of pembrolizumab as first-line ... The real-world 5-year survival rate of NSCLC cases with PD-L1 ≥ 50 % treated with first-line pembrolizumab was comparable to that in a clinical trial.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02885

Five-Year Outcomes With Pembrolizumab Versus ... With 5-year OS rates of up to 22%, these data support the continued use of pembrolizumab monotherapy as a standard-of-care treatment for ...

8. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa1801005

Pembrolizumab plus Chemotherapy in Metastatic Non– ... The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone ...

10. nature.com nature.com/articles/s41416-024-02895-1

Real-world evidence for pembrolizumab in non-small cell ... Median survival increased from about 8 months (between 7.6 and 8.6 months) for patients treated with advanced SACT in the pre-ICI era to 10.0 ...