The NRG-GI005 (COBRA) study is the first phase 3 trial to test circulating tumor DNA (ctDNA) as a predictive biomarker for adjuvant chemotherapy benefit in patients with resected colon cancer and is actively accruing patients across all United States and Canadian cooperative groups, according to a poster presented at the 2021 Gastrointestinal Cancers Symposium. Enrollment is specifically ongoing towards the phase 2 end point of the phase 2/3 trial, defined the reduction of ctDNA at 6 months to undetectable levels between arms for those with ctDNA detected at baseline.
Van K. Morris, MD, the principal investigator of the study (ClinicalTrials.gov identifier: NCT04068103), noted that there are currently no validated predictive biomarkers for stage II resected colon cancer; however, the detection of ctDNA has been associated with persistent disease after resection. The goal of this trial is to determine whether ctDNA is a predictive biomarker that can be used to select patients for chemotherapy after resection.
COBRA investigators will randomly assign 1408 patients with resected, stable stage IIA colon cancer who are deemed suitable for no adjuvant chemotherapy to standard-of-care surveillance (arm 1) or assay-directed therapy (arm 2). In arm 1, patient samples will be analyzed retrospectively for ctDNA status; in arm 2, samples will be analyzed prospectively for ctDNA to guide adjuvant chemotherapy choice.
Patients in arm B with detectable ctDNA will receive physician’s choice chemotherapy of either modified leucovorin, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX). Patients in this arm who demonstrate no detectable ctDNA will undergo active surveillance.
ctDNA will be measured by the Guardant Health LUNAR MRD ctDNA assay, which detects somatic mutations and methylation profiles to produce a “detected” or “not detected” result.
The phase 3 primary end point is relapse-free survival (RFS) at 6 months. Secondary end points include the association of ctDNA status and treatment with overall survival, RFS, and time to recurrence.
Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.
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Morris VK, Yothers G, Kopetz S, et al. Phase II/III study of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer; NRG-G1005 (COBRA). Poster presented at: Gastrointestinal Cancers Symposium; January 15-17, 2021. Abstract TPS148.