MODULE 1: Integration of Therapies Targeting BRAF and HER2 in Metastatic Colorectal Cancer (mCRC) — Dr Strickler

• Frequency of BRAF mutations and HER2 overexpression in patients with mCRC; indications, timing and optimal approaches for testing
• Updated data from the Phase II DESTINY-CRC01 study of trastuzumab deruxtecan (T-DXd) for patients with HER2-expressing mCRC
• Design, eligibility criteria and key findings from the pivotal Phase II MOUNTAINEER trial evaluating tucatinib/trastuzumab for previously treated HER2-positive mCRC
• Potential roles and ongoing investigationof T-DXd and tucatinib/trastuzumab for HER2-positive mCRC
• Spectrum and frequency of toxicities observed with T-DXd and with tucatinib/trastuzumab in patients with mCRC
• Appropriate integration of BRAF/EGFR-directed therapy into clinical practice for patients with mCRC and a BRAF V600E mutation
• Early findings with (eg, from the ANCHOR CRC trial and the BREAKWATER trial safety lead-in) and ongoing investigation of first-line BRAF-targeted therapy

MODULE 2: Optimizing the Use of Immune Checkpoint Inhibitors in the Management of mCRC — Dr Ciombor

• Key data sets informing the rational incorporation of pembrolizumab, nivolumab and nivolumab/ipilimumab for patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) mCRC
• Early results with and ongoing investigation of immune checkpoint inhibitors in combination with other systemic approaches (eg, chemotherapy, targeted therapy) for MSI-H/dMMR advanced CRC
• Biologic rationale for the investigation of immune checkpoint inhibition for microsatellite-stable (MSS) mCRC
• Clinical activity and safety observed with cabozantinib in combination with anti-PD-1/PD-L1 antibodies among patients with MSS mCRC in early-phase trials (eg, COSMIC-021 cohort 16, CAMILLA cohort 2)
• Pharmacologic and pharmacodynamic similarities and differences between cabozantinib and XL092
• Design, eligibility criteria and key efficacy and safety endpoints of the Phase III STELLAR-303 trial comparing XL092 in combination with atezolizumab to regorafenib for patients with relapsed/refractory (R/R) MSS mCRC
• Available data with and ongoing investigation of other immune checkpoint inhibitor-based strategies (eg, lenvatinib/pembrolizumab, regorafenib/pembrolizumab) for patients with MSS mCRC

MODULE 3: Evidence-Based Selection and Sequencing of Therapy for Patients with mCRC — Prof Van Cutsem

• Correlation between the location of the primary tumor (right versus left side) and outcomes with EGFR antibody-based regimens among patients with mCRC
• Design, eligibility criteria and key findings from the Phase III PARADIGM trial evaluating mFOLFOX6 with either panitumumab or bevacizumab as first-line therapy for RAS wild-type mCRC; implications for treatment decision-making
• Factors in the selection and sequencing of regorafenib, TAS-102 and EGFR antibody therapy for progressive mCRC; utility of rechallenge with EGFR antibodies after disease progression
• Long-term findings from pivotal Phase III trials assessing regorafenib and TAS-102 for patients with multiregimen-relapsed CRC
• Patient selection for and practical considerations, including optimal dosing, with the use of regorafenib for mCRC
• Available data with TAS-102 in combination with bevacizumab for patients with mCRC; emerging findings from the Phase III SUNLIGHT trial and implications for clinical practice

MODULE 4: Promising Agents and Strategies for Patients with mCRC — Dr Bekaii-Saab

• Incidence of KRAS G12C mutations in mCRC; mechanism of action of sotorasib and adagrasib
• Available efficacy and safety data with sotorasib and adagrasib monotherapy for patients with mCRC and KRAS G12C mutations
• Rationale for and early data with KRAS-targeted agents in combination with anti-EGFR therapy for mCRC
• Similarities and differences in the designs and eligibility criteria of the Phase III CodeBreaK 300 and KRYSTAL-10 trials evaluating sotorasib and adagrasib, respectively, in combination with an anti-EGFR antibody for advanced CRC
• Mechanism of action of fruquintinib; available clinical research data and potential clinical role for patients with R/R mCRC who have experienced disease progression on or are intolerant to approved standard therapies
• Other promising agents and strategies under investigation for mCRC

MODULE 5: The Changing Management Paradigm for Localized CRC — Dr Kopetz

• Benefits and limitations of current approaches for surveillance and treatment decision-making for patients with localized CRC who have undergone curative-intent therapy
• Mechanistic rationale for and available data (eg, from the CIRCULATE-Japan study) with the use of circulating tumor DNA (ctDNA)/minimal residual disease (MRD) monitoring in the management of localized CRC
• Active studies (eg, CIRCULATE-US, BESPOKE CRC) examining the clinical utility of ctDNA/MRD testing in guiding treatment decision-making and monitoring for recurrence; potential clinical impact
• Biologic rationale for the use of immune checkpoint inhibitors for patients with localized CRC
• Available findings from the Phase II NICHE and NICHE-2 trials investigating the efficacy and safety of nivolumab/ipilimumab as neoadjuvant therapy for patients with nonmetastatic CRC
• Ongoing Phase III trials evaluating the role of immune checkpoint inhibitors in therapy for localized CRC