A Study of Local Ablative Therapy (LAT) in People With Non-Small Cell Lung Cancer (NSCLC)

NCT05429320 | Completed Phase 2 DMC FDA Device

• 1 other identifier: 21-465
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to see whether receiving local ablative therapy (LAT) when minimal residual disease/MRD levels are rising can reduce MRD levels and control metastatic non-small cell lung cancer/NSCLC longer compared to systemic therapy.

Conditions

Non-small Cell Lung Cancer; Metastatic Non Small Cell Lung Cancer; Nsclc; NSCLC Stage IV; Minimal Residual Disease; Non Small Cell Lung Cancer Metastatic

Keywords

Non-small Cell Lung Cancer; Non Small Cell Lung Cancer Metastatic; Metastatic Non Small Cell Lung Cancer; NSCLC; NSCLC Stage IV; Minimal Residual Disease; MRD; 21-465; Memorial Sloan Kettering Cancer Center

Outcome Measures

Primary Outcomes (2)

• Measure the reduction in mean variant allele frequency/VAF by 6 months after Local Ablative Therapy/LAT

  To determine whether Local Ablative Therapy/LAT (ablation to all sites of disease) causes a reduction in mean variant allele frequency/VAF by 6 months after LAT in patients with metastatic NSCLC who have non-responding variant allele frequency/NR-VAF (\<50% reduction in mean VAF) but no radiographic progression of disease. Mean VAF: Mean VAF will be defined by the VAF of each relevant mutation divided by the total number of mutations

  6 months

• Progression Free Survival/PFS

  PFS will be evaluated through imaging obtained Q3 months +/-2 weeks after enrollment. Progression will be evaluated by RECIST 1.1 guidelines. To determine whether LAT improves PFS in patients with metastatic NSCLC who have NR-VAF but no radiographic progression of disease compared to patients who continue systemic therapy.

  3 months +/- 2 weeks after enrollment

Study Arms (3)

Part I

EXPERIMENTAL

In part I, 33 patients with metastatic NSCLC with: a) NR-VAF but b) without radiographic progression of disease, will be treated with LAT to determine if ablation to all sites of disease leads to acceptable rates of mean VAF reduction, thus indicating a discernible molecular/clinical response in this subgroup of patients with metastatic disease.

Procedure: Local ablative therapy; Other: Blood collection to assess for ctDNA

Part II - standard of care

ACTIVE COMPARATOR

If the appropriate criteria are met in part I,, in part II 60 patients with NR-VAF but without radiographic progression of disease will be randomized to one of two arms: continuation of systemic therapy (standard of care) vs. ablation to all sites of disease (experimental arm), with a primary endpoint of progression free survival.

Other: Blood collection to assess for ctDNA

Part II - ablation to all sites of disease (experimental arm)

EXPERIMENTAL

If the appropriate criteria are met in part I,, in part II 60 patients with NR-VAF but without radiographic progression of disease will be randomized to one of two arms: continuation of systemic therapy (standard of care) vs. ablation to all sites of disease (experimental arm), with a primary endpoint of progression free survival.

Procedure: Local ablative therapy; Other: Blood collection to assess for ctDNA

Interventions

Blood collection to assess for ctDNA OTHER

Participants will undergo ctDNA collection in conjunction with their standard of care therapy.

Part I; Part II - ablation to all sites of disease (experimental arm); Part II - standard of care

Local ablative therapy PROCEDURE

In part I, 33 patients with metastatic NSCLC with: a) NR-VAF but b) without radiographic progression of disease, will be treated with LAT. In Part II of the study, patients will be randomized to standard of care (continuation of systemic therapy) vs. LAT to all sites of disease

Also known as: LAT

Part I; Part II - ablation to all sites of disease (experimental arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Monitoring Phase
• Stage IV NSCLC. Note that patients are eligible for the study if they have received definitive treatment for early stage disease, presuming that they remain candidates for local ablative therapy (LAT).
• AJCC 8th Edition Stage IV disease
• Has had up to four cycles of standard first-line systemic therapy +/- 3 weeks, defined as: a) platinum-doublet chemotherapy, b) ICI, or c) platinum-doublet chemotherapy + ICI at the baseline ctDNA draw being used for the study.
• Patient initiated their ctDNA blood draws during their first 4 cycles of first line systemic therapy +/- 3 weeks (during their first 4 cycles, or up to 3 weeks before/after they have begun/ended their first 4 cycles of systemic therapy
• Ten or less metastatic lesions (Note that this criterion includes lesions, not sites: 3 brain metastases = 3 lesions).
• ° Imaging defining extent of disease should be performed within 4 weeks of ctDNA blood draw
• PET/CT scan or CT scan of the chest/abdomen/pelvis within 4 weeks of blood draw for ctDNA analysis
• MRI or CT scan of the brain at baseline, AND within 4 weeks of blood draw for ctDNA analysis (optional, per discretion of treating physician)
• All lesions amenable to LAT.
• o Note that patients who receive local therapy (radiation, surgery, or RFA) prior to enrollment for palliative purposes or to CNS lesions are eligible for enrollment if:
• a) all other eligibility criteria are met and b) at least one other lesion is amenable to LAT and is RECIST evaluable. All lesions treated for palliative purposes will also be counted towards the total number of lesions.
• At least one site of measurable disease
• ECOG Performance status 0 - 2.
• Age ≥ 18 years.

You may not qualify if:

• At the time of therapeutic phase enrollment, complete response radiographically (no lesions to target)
• Patients with CNS-only disease (due to limited capacity of peripheral blood ctDNA to detect CNS lesions)
• Planned treatment by targeted agents (e.g. tyrosine kinase inhibitors) or patient not a candidate for systemic therapy
• Serious medical co-morbidities precluding radiotherapy or ablation, determined at the discretion of the treating investigator.
• At the time of therapeutic phase enrollment, pregnant or lactating women.
• Physical limitation to undergo stereotactic radiotherapy.
• Other active malignancy within the last year except for basal cell carcinoma of the skin and in situ malignancy even if without evidence of disease.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (9)

Hartford Healthcare ALLIANCE (Data collection only)

Hartford, Connecticut, 06102, United States

Location

BAPTIST ALLIANCE - MCI (Data collection only)

Miami, Florida, 33143, United States

Location

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm, Residual

Interventions

Circulating Tumor DNA

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cell-Free Nucleic Acids; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides; DNA, Neoplasm; DNA

Study Officials

• Daniel Gomez, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2022
• First Posted: June 23, 2022
• Study Start: June 15, 2022
• Primary Completion: January 28, 2026
• Study Completion: January 28, 2026
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (9)