Abstract 4029: Project Cure CRC: advancing colorectal cancer research and personalized treatment through a CRC platform clinical trial

Abstract Background: The Colorectal Cancer Alliance (Alliance) established Project Cure CRC to support critical research breakthroughs in colorectal cancer (CRC), driving advancements in treatment and improving patient outcomes. CRC is among the most prevalent and fatal cancers worldwide, accounting for over 1.9 million new cases and 935, 000 deaths annually. A significant challenge in treating CRC is its high genetic variability among patients, leading to differing responses to standard therapies and underscoring the urgent need for personalized approaches. Many cases involve mutations linked to resistance to conventional treatments, resulting in poor prognoses and limited options for these patients. Methods: Project Cure CRC initiated a targeted Request for Proposals (RFP) informed by insights from the previous Cure CRC Summit. This effort received 250 submissions, many aiming to fund clinical trials testing novel therapies targeting CRC directly or enhancing the tumor microenvironment to improve immunotherapy effectiveness. The Alliance intends to invest $100 million in research over the next three years; funding individual trials was deemed insufficient for achieving the desired impact. After extensive exploration of various strategies, the Alliance is establishing a multi-center colorectal cancer platform trial to focus on curative research in four key areas: Neoadjuvant therapy for CRC, Minimal residual disease-positive patients with no radiographic evidence of disease, Perioperative surgery of metastatic disease, Metastatic and oligometastatic disease. Results: To advance treatment options, accelerate regulatory approvals, and increase the 5-year survival rate for metastatic CRC from 13% to 35%, the Alliance is leading an adaptive, multi-site platform trial tailored to high-risk CRC cases. Modeled after successful trials for breast cancer, AML, multiple myeloma, and PDAC, this innovative trial design enables researchers to test multiple therapies simultaneously through multiple trial arms. The trial will use real-time data and Bayesian statistical approaches to adaptively select and refine effective treatments. A synthetic cohort will also be created in collaboration with the FDA, minimizing the need for some patients to receive only standard-of-care therapies. By integrating cutting-edge biomarker research, the platform trial will identify the most effective treatments for specific CRC tumor molecular subtypes. Conclusions: The CRC platform trial will establish a collaborative, data-driven framework to accelerate the translation of research into clinical application. By incorporating ongoing adjustments and emphasizing targeted therapies, the trial aligns with the Alliance’s mission to deliver impactful research and offer personalized, effective treatments to CRC patients with limited options under current care standards. Citation Format: Kimberly Lynn Newcomer, David Fenstermacher. Project Cure CRC: advancing colorectal cancer research and personalized treatment through a CRC platform clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4029.