A Multicenter Randomized Open-Label Trial Evaluating ctDNA-Guided Interruption Versus Standard of Care Immune-Checkpoint Inhibitor (ICI) Therapy In Patients With Advanced / Metastatic Solid Tumors.

Starting soon · Not applicable

Conditions studied: NSCLC (Advanced Non-small Cell Lung Cancer), NSCLC (Non-small Cell Lung Cancer), NSCLC (Non-small Cell Lung Carcinoma), NSCLC, Melanoma (Skin Cancer), Melanoma (Skin) Stage IV, CRC, MSI High Colorectal Cancer, DMMR Colorectal Cancer, RCC, Renal Cell Cancer, RCC, Solid Tumors, Metastatic Solid Tumors, Advanced Solid Tumors, Advanced Solid Tumors Cancer

In brief

This is a multicenter, open-label, randomized (1:1) trial designed to evaluate whether ctDNA-guided interruption of immune-checkpoint inhibitor (ICI) therapy provides comparable survival to standard of care (SoC) continuous ICI therapy in patients with histologically confirmed advanced/metastatic non-small cell lung cancer (NSCLC), melanoma, microsatellite instability-high (MSI-High)/Deficient Mismatch Repair (dMMR) colorectal cancer (CRC), renal cell carcinoma (RCC) and other solid tumors. This study will be conducted in up to 100 sites.

Key facts

Study ID

NCT07689812

Run by

Natera, Inc.

People needed

920

Starts

2026-12-01

Expected to finish

2034-03-01

Last updated by the study team

2026-08-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• General inclusion criteria includes the following selection criteria to be eligible for inclusion in any aspect of the study. Eligibility will be assessed by the investigator:
• Signed Informed consent
• Age ≥ 18 years
• ECOG 0-2.
• Histologically confirmed advanced/metastatic solid tumors including:
• Melanoma: Unresectable recurrent, advanced, or metastatic
• NSCLC: Advanced or metastatic
• MSI-High/dMMR CRC: Metastatic
• RCC: Unresectable recurrent, advanced, or metastatic
• Other: Metastatic solid tumors
• Received first line ICI monotherapy or dual-ICI therapy (e.g., PD-1/CTLA-4 combination therapy) for a minimum of 12 months (maximum of 15 months) for NSCLC, RCC \& other metastatic solid tumors, or for a minimum of 6 months (maximum of 9 months) for melanoma and MSI-High /dMMR CRC. Exceptions permitted:
• For patients with NSCLC: First line platinum-based chemo-ICI regimens if on maintenance ICI +/- pemetrexed.
• For patients with melanoma: nivolumab/relatlimab is permissible.
• Radiographic CR/PR: Participants must have CR or PR at the last assessment performed within 6 weeks before randomization according to RECIST v1.1 using a diagnostic CT and/or MRI. Radiographic assessment must be confirmed by the BICR prior to randomization.
• Known ctDNA-negative with a tissue-informed assay
• ≥ 2 consecutive ctDNA-negative results at least 6 weeks apart; last test within 1 month of enrollment.
• Note: A confirmatory Signatera Genome negative test must be completed at enrollment if previous ctDNA testing performed for clinical care was done with a test other than Signatera Genome.
• Adequate organ function:
• Hematology: ANC ≥1500/μL; Platelets ≥100000/μL;Hemoglobin ≥9.0g/dL;
• Renal: Serum Cr ≤1.5×ULN or calculated CrCl ≥60 mL/min (using Cock-Gault formula);
• Hepatic: Total bilirubin ≤1.5 ×ULN or, for participants with total bilirubin levels >1.5×ULN, direct bilirubin within normal limits; AST (SGOT) and ALT (SGPT) ≤2.5×ULN;
• Coagulation: INR or PT, activated partial thromboplastin time (APTT) ≤1.5×ULN Note: Laboratory assessments performed as part of standard of care evaluations during immunotherapy treatment administration may be used to satisfy these eligibility criteria, provided they are obtained within 28 days of enrollment.
• Recovery to baseline or ≤ Grade 1 common terminology criteria for adverse events (CTCAE) v6 from AE(s) related to any prior treatments unless AE(s) are deemed clinically non-significant (e.g., Grade 2 alopecia) by the Investigator and/or stable on supportive therapy.
• No prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since completion of definitive therapy
• Participants must be willing and able to comply with study visits, treatment plans, laboratory tests, and other study procedures

You may not qualify if…

• Patients are not eligible for the study if they meet any of the following criteria, as assessed by the investigator:
• Available alternate treatment options with curative intent, e.g. surgery and / or RT and / or Chemotherapy.
• Symptomatic or progressing CNS metastases; or presence of leptomeningeal disease.
• Patient has active autoimmune disease that required systemic treatment in the past 2 years, is immunocompromised in the opinion of the Investigator, or is receiving systemic immunosuppressive treatment. (Note: Participants with splenectomy are allowed.) Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment.
• Patient is receiving systemic steroid therapy ≤3 days prior to enrollment or receiving any other form of immunosuppressive medication with the exception of daily steroid replacement therapy. Note: Use of inhaled corticosteroids, local steroid injection, or steroid eye drops is allowed.
• Had allogeneic tissue/solid organ transplantation.
• Interstitial lung disease or history of pneumonitis that has required oral or IV steroids. Note: Patients with lymphangitic carcinomatosis secondary to NSCLC can be considered as eligible.
• Has received or will receive a live vaccine within 30 days prior to enrollment (seasonal flu vaccines that do not contain live vaccine are permitted).
• Active infection requiring intravenous systemic therapy.
• Known history of human immunodeficiency virus (HIV).
• Known active Hepatitis B or C.
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study.
• Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of enrollment.
• Use of any commercial ctDNA or liquid biopsy monitoring outside of the study protocol during the treatment monitoring phase within the protocol.

Full record on ClinicalTrials.gov

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