Use of Serial Plasma NGS as a New Efficacy Metric to Guide Immunotherapy Treatment Discontinuation

NCT06146920 | Active Not Recruiting

• 1 other identifier: 23-357
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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?

Conditions

Melanoma; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Evaluate the 12month disease-free survival (DFS) in ctDNA negative patients

  Disease-free survival is defined as the time of determination of ctDNA negativity to the earlier of progression or death. This will be measured in days.

  12 months

Secondary Outcomes (1)

• Overall survival of the ctDNA negative cohort

  12 months

Study Arms (1)

Active Surveillance

OTHER

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.

Other: Evaluation of ctDNA using the F1T after 1 year of immunotherapy

Interventions

Evaluation of ctDNA using the F1T after 1 year of immunotherapy OTHER

Patients with evidence of disease control after at least 10months of an ICI-based therapy will initially undergo a pre-screen. In patients with successful F1CDx baseline tissue testing whole blood will be collected and evaluated for plasma ctDNA measurement. If there is detectable ctDNA during the pre-screening period, patients will be excluded from enrollment. If there is no detectable ctDNA, patients will be eligible to screen and enroll in the main study. If enrolled, patients will stop ICI- based treatment and continue with serial ctDNA at pre-specified timepoints. The treating physician will not be blinded to the serial ctDNA results There will be no proscriptive therapeutic measures outlined if ctDNA becomes detectable while on study.

Also known as: Discontinue Immune Checkpoint Inhibitor

Active Surveillance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients age \> 18) with unresectable, metastatic melanoma (cutaneous, acral, mucosal) or NSCLC who have evidence of disease control after at least 12 months of ICI based therapy (pembrolizumab, nivolumab, nivolumab-relatimab, ipilimumab/nivolumab, atezolizumab, ipilimumab, durvalumab, cemiplimab) with or without chemotherapy in the case of NSCLC. Any line of therapy is permitted with the exception of adjuvant therapy
• Participants must be actively receiving standard of care ICI-based therapy (ICI monotherapy or in combination)
• At time of enrollment patients must have received at least 12months (+/- 4 weeks) from the start of anti-PD-1 therapy and have not experienced a toxicity that prevented them from continuing therapy.
• Participants must have evidence of disease control (stable disease, partial response, or complete response) that is maintained on restaging CT scans or PET CT scans obtained at 12 months (+/- 4 weeks) from the start of initial ICI therapy
• Prior radiation to any site is allowed
• Available tumor tissue (archival) for baseline tissue testing with FoundationOne CDx or previous FoundationOne CDx testing results (within 2 years and prior test results must be after June 30, 2021)
• Life expectancy of greater than 3 months
• Participants with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment are eligible for this trial.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Participants with clinical or radiographic evidence of progressive disease in the 3 months prior to consideration of screening and enrollment
• Participants who are receiving an investigational agent (s)
• Participants who have had ICI discontinued due an immune-related adverse event.
• Patients with a history of an irAE but resumed ICI therapy and are receiving ICI at the time of screening are eligible to enroll.
• Participants on \> 10mg of oral prednisone or its equivalent for treatment of ongoing immune-related toxicity.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia, endocrine toxicity requiring chronic supplementation
• Participants with a concurrent, active malignancy
• Participants in whom F1CDx generation fails
• Participants without available tumor tissue for F1CDx test result or prior F1CDx

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Foundation Medicine: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung

Interventions

Immunotherapy

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Study Officials

• Meghan Mooradian, MD

  Massachusetts General Brigham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: All consented participants with evidence of disease control / response after at least 1 year of immune checkpoint inhibition (monotherapy or in combination) with negative ctDNA will be invited to stop systemic therapy and continue with active surveillance.

Study Record Dates

• First Submitted: November 10, 2023
• First Posted: November 27, 2023
• Study Start: January 10, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)