Innovative ctDNA Testing Drives Progress in NSCLC Research

Holographic concept of lung cancer display, lung disease: © catalin - stock.adobe.com

The phase 3 TROPION-Lung12 trial (NCT06564844) evaluating adjuvant treatment regimens for patients with stage I adenocarcinoma non–small cell lung cancer (NSCLC) has tested for eligibility its first patient with the investigational GRAIL NSCLC circulating tumor (ct) DNA assay.¹

This research, approved under an FDA Investigational Device Exemption (IDE) held by GRAIL, uses the biotechnology company's innovative targeted methylation platform to identify ctDNA. The method uses blood only, removing the need for tissue biopsies or custom panel creation and allows for seamless integration into pharmaceutical clinical trials.

In TROPION-Lung12, the GRAIL assay will be given before surgery to identify patients who are eligible for post-surgery randomization into a cohort receiving the adjuvant treatment regimen. Data on the assay’s accuracy and effectiveness were previously reported in the Journal of Thoracic Oncology and highlighted at the 2023 North America Conference on Lung Cancer.

“We’re excited to continue our strategic collaboration with AstraZeneca with the use of our novel assay in the TROPION-Lung12 study. We hope this study will further demonstrate the potential of GRAIL’s Methylation Platform to enhance patient selection for cancer treatment,” said Harpal Kumar, president, international business & biopharma, at GRAIL, in a press release.

“GRAIL’s ctDNA detection approach, which does not require tumor tissue, has the potential to offer oncologists a rapid, accessible method to help refine patients’ diagnostic and prognostic profiles for better guided cancer therapy. This is one of the first times a ctDNA assay has been used in a clinical trial of early-stage lung cancer patients to identify those most likely to benefit from further treatment. As such, we hope this approach could provide substantial additional benefit for patients diagnosed with stage 1 lung cancer,” continued Kumar.

About the TROPION-Lung12 Study

TROPION-Lung12 is a randomized, open-label, global study evaluating the efficacy and safety of adjuvant datopotamab deruxtecan (Dato-DXd) in combination with rilvegostomig, relative to standard-of-care, in patients with stage I adenocarcinoma NSCLC who are ctDNA-positive, as determined by the Sponsor-designated ctDNA assay. If not positive, patients must have at least 1 high-risk pathological feature.²

The study enrolled patients with histologically documented treatment-naive stage I adenocarcinoma NSCLC with complete surgical resection, no evidence of disease post-surgery, and a pre-surgical ctDNA-positive result or the presence of at least 1 high-risk pathological feature. Patients were required to have an ECOG performance status of 0 or 1, a life expectancy of more than 6 months, complete recovery after surgery, and adequate bone marrow reserve and organ function.

In the first group, patients will receive Dato-DXd in combination with rilvegostomig intravenously (IV) every 3 weeks. In the second experimental group patients will receive rilvegostomig monotherapy via IV infusion every 3 weeks. Finally, patients in the standard of care group will undergo observation or will receive the investigator's choice of chemotherapy.

“In TROPION-Lung12, screening for ctDNA is intended to identify the patients at an increased risk of disease recurrence after surgery and thus most likely to benefit from adjuvant therapy,” said Cristian Massacesi, MD, chief medical officer and oncology chief development officer, AstraZeneca, in a press release.1 “The novel strategy we are deploying in this trial illustrates our commitment to both detect cancer earlier and use those early insights to enable more personalized treatment decisions for the benefit of patients.”

REFERENCES

1. GRAIL announces first patient tested with blood-based assay in global phase 3 adjuvant lung cancer study. News release. GRAIL, Inc. November 18, 2024. Accessed November 19, 2024. https://tinyurl.com/ycx32vtf

2. A phase III, randomised study of adjuvant Dato-DXd in combination with rilvegostomig or rilvegostomig monotherapy versus standard of care, following complete tumour resection, in participants with stage I adenocarcinoma NSCLC who are ctDNA-positive or have high-risk pathological reatures (TROPION-Lung12). ClinicalTrials.gov. Updated November 18, 2024. Accessed November 19, 2024. https://clinicaltrials.gov/study/NCT06564844