Explore the Agenda
8:00 am Check In & Registration
8:45 am Chair’s Opening Remarks
Designing Innovative Combination Strategies That Target Intrinsic Resistance & Pathway Crosstalk to Deliver Broader, More Durable RAS Control
9:00 am Advancing PLK1 Targeted Therapy to Transform Outcomes in RAS Mutant Metastatic Colorectal Cancer
- Leveraging PLK1 based synthetic lethality to address RAS mutant metastatic colorectal cancer with a highly selective PLK-1 inhibitor, onvansertib
- Demonstrating potentially practice changing clinical activity and tolerability of onvansertib with FOLFIRI/bev in front line RAS-mut mCRC in a randomized controlled Phase II study
- Defining a clinical path toward approvability through ongoing first line development and combination with a standard chemotherapy backbone in an area of high unmet need with limited advancements
9:30 am Disruption of the RAS-PI3Kα Interaction Provides Enhanced Efficacy in Combination Mutant KRAS Targeting Therapies
- Targeting oncogenic RAS-PI3Kα signaling with small molecules that selectively block the RAS-PIK3CA interaction while preserving homeostatic PI3Kα function, improving tolerability in ways traditional active site inhibitors cannot
- Enhancing antitumor activity by combining selective RAS-PIK3CA inhibition with MAPK pathway agents, achieving dramatic efficacy improvements in preclinical RAS driven cancer models
- Countering intrinsic & adaptive resistance to direct mutant KRAS inhibitors through blockage of WT RAS-driven activation of the PI3K/AKT pathway
10:00 am Morning Break & Networking
11:00 am Expanding Patient Reach: Developing Novel INCB161734 (KRAS G12D Inhibitors) Combinations That Work Across Heterogeneous Tumors
- Combining KRAS inhibitors with orthogonal agents in novel ways to increase the depth and breadth of efficacy in heterogenous tumors
- Reevaluating ways to broaden, not shrink, the treatable KRAS G12D patient population, avoiding combinations that only benefit narrow biomarker defined subsets
- Mutant-selective KRAS inhibitors enable maximal mutant KRAS inhibition while limiting off-tumor to the extent possible off-tumor activity
11:30 am Expanding the Druggable Landscape: Targeting Signalling, Cytoskeletal & Chromatin Pathways to Unlock Next-Generation RAS Combination Strategies
- Identifying novel druggable vulnerabilities across signalling, cytoskeletal, and chromatin networks to open new therapeutic opportunities beyond conventional targets
- Targeting protein-protein interactions and defining optimal developmental treatment windows to maximize inhibitor impact while improving translational success
- Leveraging RAC and RAS pathway biology alongside a predictive combination platform to design rational therapies, validated through pioneering brain cancer research and published studies
12:00 pm Lunch Break & Networking
Building Effective Combination Strategies Across the Complexity of RAS-Driven Cancers
1:00 pm Panel Discussion: How Do We Build Combination Strategies That Work Across KRAS Alleles, Co Mutations, & Tumor Types?
- How do KRAS alleles, co‑mutations, and tumor lineage reshape dependency and escape, and what does that mean for choosing the right combination backbone?
- Which combinations have true cross‑context potential, and which are only effective in specific molecular or tumor‑type settings?
- How should we prioritise combinations that balance biological rationale, toxicity constraints, and real‑world feasibility across heterogeneous patient populations?
2:00 pm TRIM7 Inhibition Blocks RTK/RAS Pathway Driven Tumor Proliferation Independent of Mutation & in the Setting of KRASi Resistance
- KT-300 is a covalent small molecule inhibitor of the E3 ubiquitin ligase TRIM7, which is hyperactivated in RTK/RAS driven cancers, enabling broad activity across tumor types and offering a potential path beyond mutation-specific targeting strategies
- KT-300 is active in the setting of KRAS inhibitor resistance, and may support sustained pathway suppression and improve the potential for durable responses in RAS-driven cancers
- Combined blockade with KT-300 and upstream RAS-pathway inhibition (e.g.; anti- EGFR, KRASi, etc.) enhance anti-tumor responses, creating broad opportunities for rationale combinations
Optimizing the Translation of Combination Therapies into the Clinic by Delving into Trial Design, Toxicity & Real World Strategy
2:30 pm Advancing First Line Care for KRAS G12C positive & PD L1 negative NSCLC: Optimizing Targeted Therapy + Chemotherapy for a High-Unmet- Need Population
- Highlighting the distinct clinical profile and poor real world outcomes of KRAS G12C +ve / PD L1 -ve NSCLC, underscoring why this population represents a critical unmet need in first line treatment.
- Demonstrating how a cleaner, biomarker defined trial design and a safer chemo + targeted therapy approach may avoid early immunotherapy related toxicities while preserving future treatment options
- Exploring the role of translational research, including proteomics, transcriptomics, and longitudinal blood sampling, in understanding treatment response, resistance, and sequencing strategies across the patient journey