Abstract 158TiP
Background
Three or 6 months of fluoropyrimidines plus oxaliplatin is the standard adj therapy for stage III and high-risk stage II colon cancer, but 20-25% of pts relapse. CtDNA is a promising biomarker of minimal residual disease (MRD) after primary tumor resection and a potential guide in the adj treatment decision-making process. Indeed, ctDNA-positivity after surgery or at the end of adj therapy is associated with higher risk of recurrence. Intensifying the adj and/or the post-adj treatment could be a valuable strategy in these cases. CtDNA clearance has been suggested as a predictor of long-term clinical outcome.
Trial design
ERASE-CRC is a prospective, open-label, multicentre study, including 3 phase 2 trials enrolling ctDNA-positive (+) pts with radically resected stage III or high-risk stage II adenocarcinoma of the colon or intraperitoneal rectum. CtDNA is centrally assessed through a tissue-informed method, F1Tracker. In the ERASE-CRC Part 1 study, pts that are ctDNA+ after surgery (2-6 weeks) are randomized 1:1 to 6 months of either FOLFOX or CAPOX at investigators’ choice (arm A) versus FOLFOXIRI (arm B). In the ERASE-HER2 study, ctDNA+ pts with HER2 amplified and RAS wild-type tumors received FOLFOX plus trastuzumab and tucatinib for 12 cycles. In ERASE-CRC Part 2 study, ctDNA+ pts after the end of an oxaliplatin-based adj therapy (either in the context or outside Part 1 or ERASE-HER2) are randomized 1:2 to observation (arm A) or trifluridine/tipiracil for 6 cycles (arm B). The primary endpoint is the ctDNA clearance rate (CR) after the adj (Part 1 and ERASE-HER2) or the post-adj treatment (Part 2). 300 pts will be randomized in Part 1 to detect a 15% difference in ctDNA CR between arms B and A (65% vs 50%), and 1-sided alpha and beta errors of 0.05 and 0.2, respectively. 18 pts will be enrolled in ERASE-HER2 to observe a ctDNA CR of 80% with the targeted treatment and ctDNA clearance should be observed in 13 cases to consider the strategy promising. Finally, 159 pts will be randomized in Part 2 to detect a 15% difference in ctDNA CR between arms B and A ( 20% vs 5%), and 1-sided alpha and beta errors of 0.05 and 0.2, respectively.
Clinical trial identification
NCT05062889.
Legal entity responsible for the study
GONO Foundation.
Funding
GONO Foundation, Foundation Medicine, Servier, Seagen, FICOG, GISCAD, GOIM.
Disclosure
S. Lonardi: Financial Interests, Personal and Institutional, Funding, Honoraria, Consulting or Advisory Role, Speakers' Bureau: Amgen, Roche; Financial Interests, Personal and Institutional, Funding, Consulting or Advisory Role, Speakers' Bureau: Bayer; Financial Interests, Personal and Institutional, Funding, Consulting or Advisory Role: Astellas, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Funding: Bayer, Hutchinson, Incyte, Mirati, Pfizer; Financial Interests, Personal and Institutional, Funding, Honoraria, Consulting or Advisory Role: Bristol Myers Squibb, Merck Sharp & Dohme, Servier; Financial Interests, Personal and Institutional, Funding, Honoraria, Consulting or Advisory Role: Merck Serono; Financial Interests, Personal, Other, Honoraria, Consulting or Advisory Role: Incyte, Eli Lilly; Financial Interests, Personal, Other, honoraria: GSK, Pierre Fabre. C. Antoniotti: Financial Interests, Personal, Other, Honoraria, Travel, Accommodation, Expenses: Merck. F. Pietrantonio: Financial Interests, Personal, Speaker’s Bureau, Research Funding, Consulting or Advisory Role: Amgen, Merck Serono; Financial Interests, Personal, Funding, speaker's Bureau, Consulting or Advisory Role: Lilly; Financial Interests, Personal, Speaker’s Bureau, Consulting or Advisory Role: Servier, Incyte, MSD, GSK; Financial Interests, Personal and Institutional, Funding, Consulting or Advisory Role: AstraZeneca, Bristol Myers Squibb, Bayer; Financial Interests, Personal, Other, Consulting or Advisory Role: Daiichi Sankyo, Astellas Pharma, Takeda; Financial Interests, Personal and Institutional, Speaker’s Bureau, Research Funding: Roche; Financial Interests, Speaker’s Bureau: Pierre Fabre. L. Salvatore: Financial Interests, Personal, Funding, Travel, Accommodation, Expenses, Honoraria, Travel, Accommodation, Expenses, Consulting or Advisory Role: Merck Serono; Financial Interests, Personal, Other, Travel, Accommodation, Expenses, Honoraria, Travel, Accommodation, Expenses, Consulting or Advisory Role: Servier, Pierre Fabre; Financial Interests, Personal, Other, Honoraria, Consulting or Advisory Role: Amgen, AstraZeneca, MSD, GSK, Incyte, Takeda; Financial Interests, Personal, Other, Travel, Accommodation, Expenses, Honoraria, Travel, Accommodation, Expenses, Consulting or Advisory Role: Bayer. G. Masi: Financial Interests, Personal, Other, Consulting or Advisory Role: AstraZeneca, Eisai, MSD Oncology, Roche; Financial Interests, Institutional, Funding, Patents, Royalties, Other Intellectual Property: Terumo. M. Fassan: Financial Interests, Personal, Funding, Consulting or Advisory Role: Astellas Pharma; Financial Interests, Personal, Invited Speaker, Consulting or Advisory Role: GSK, Roche, AstraZeneca, GSK, MSD Oncology, Pierre Fabre, Amgen, Incyte, Novartis, Lilly, Janssen; Financial Interests, Personal, Funding: QED Therapeutics, Macrophage Pharma, Diaceutics. C. Cremolini: Financial Interests, Funding, Honoraria, Consulting or Advisory Role: Roche, Bayer; Financial Interests, Other, Honoraria, Consulting or Advisory Role: Amgen, MSD; Financial Interests, Speaker’s Bureau, Honoraria, Consulting or Advisory Role: Pierre Fabre; Financial Interests, Invited Speaker, Consulting or Advisory Role: Nordic Bioscience; Financial Interests, Speaker’s Bureau, Honoraria, Funding: Servier, Merck. All other authors have declared no conflicts of interest.