PRE-CONFERENCE WORKSHOP
8:00 am Morning Check-In & Light Breakfast
Workshop A
8:30 am Debunking Safety & Efficacy Concerns Surrounding Targeting Wild Type KRAS to Induced Tumor Regression
Synopsis
Wild type KRAS continues to present a huge challenge in selectively targeting mutant variants implicated in cancer due to its structural similarity and essential cellular functions. Debate surrounds the feasibility and safety of directly targeting wild type KRAS, with concerns over potential off-target effects. Despite advances in structural and functional studies, these findings are yet to translate into clinically viable therapies drawing an increasing need for thought leaders to debate the potential consequences and mitigations.
This workshop will discuss:
• Can we target wild type KRAS? If so, can we differentiate between active and inactive states?
• How can we minimize toxicity in RAS targeted therapies?
• How to develop robust pre-clinical models to assess the efficacy and safety of wild type KRAStargeting agents
• How to combine wild type KRAS inhibitors with other therapeutic agents?
Workshop B
8:30 am Exploring Optimal Combinations within Vertical & Parallel Pathways to Clinically Target NSCLC & Beyond
Synopsis
The validation and clinical progression of novel agents targeting critical nodes in vertical and parallel signaling pathways are crucial to address adaptive and acquired resistance. However, informing disease-specific combination regimens for NSCLC and other RAS pathway-driven malignancies is no easy feat, with challenges surrounding synergistic drug design, cancer histotypes, and diverse patient profiles. This workshop will review the latest developments in targeting the RAS/MAPK pathway, parallel signaling cascades, address concerns for treating diverse oncology landscapes, and provide a clinical update on synergistic agents to help de-risk future combination regimes.
This workshop will discuss:
• Novel agents/approaches to target critical nodes in the vertical RAS/MAPK pathway and parallel signaling pathways to address adaptive and acquired resistance
• Disease-specific approaches/concerns for targeting NSCLC and additional RAS pathway-driven tumor types
• Translation from pre-clinical to clinical studies and update on new clinical data
10:30 am Morning Networking Break
Synopsis
An opportunity to network, discuss and collaborate with like-minded leaders
Workshop C
11:30 am Leveraging Systems Biology & Pharmacology Tools to Elucidate RAS Regulatory Networks & Reveal New Therapeutic Targets
Synopsis
Systems biology and pharmacology has increasingly become instrumental in dissecting complex RAS networks including vertical and parallel pathways. However the entire RAS interactome is yet to be elucidated leaving untapped opportunity to overcome acquired resistance, inform combination strategies and target previously undrugged mutations and isoforms. This workshop will explore the molecular biology, omics and pharmacology tools used to elucidate RAS pathways and noncanonical approaches to target the broader oncogenic RAS landscape.
This workshop will discuss:
• What do we know about RAS networks, and what further dissection of pathways and interaction networks is needed?
• What is the utility of implementing quantitative multiplexed proteomics and how does this elucidate the RAS interactome? How can these assays inform combination therapies?
• How to leverage genomics, molecular biology and pharmacology tools to elucidate non-canonical approaches to target oncogenic RAS?
• What is the scope targeting non-oncogene addiction?
Workshop D
11:30 am Addressing Acquired Resistance by Predicting Clinical Trial Outcomes & Improving Patient Response Rates
Synopsis
Acquired resistance to mutant-selective RAS inhibitors, including approved and investigational KRAS G12C inhibitors, presents significant challenge. It is critical that we not only consider the efficacy of direct inhibitor targeting but debate how additional drugging of vertical pathways can be crucial to overcoming feedback mechanisms. As recent advances in the last six months have uncovered novel mechanisms of RAS inhibitor resistance, this workshop will deep-dive into how we can improve patient response rates with genomic and biomarker data.
This workshop will discuss:
• How to identify and characterize mechanisms underlying RAS acquired resistance
• How to predict clinical trial outcomes before the clinic considering tumor heterogeneity
• How to develop predictive biomarkers for identifying patients at risk of resistance
• How to optimize the dosing and scheduling of single or combination therapies to delay or overcome resistance
Session Reserved for resistanceBio
1:30 pm Lunch & Networking Break
Workshop E
2:30 pm Exploring Mechanisms of Action & Navigating Agent Synergy in the Pre-clinic to Improve the Efficacy of Combination Therapies
Synopsis
Current pre-clinical exploration in combination strategies for targeting RAS-driven tumors is underscored by selecting synergistic agents with complementary mechanisms to overcome acquired resistance. Amidst the emergence of diverse modalities, a deeper understanding of the interplay between targeted proteins and up/downstream pathways is crucial, alongside toxicity risks. This workshop will shed light on promising combinations in pre-clinical models, debate novel drug pairs and direct/indirect co-treatments. These insights will drive the optimization of combination regimens to advance personalized cancer treatment paradigms for patients with unmet need.
This workshop will discuss:
• How to effectively identify synergistic agents with complementary mechanisms of action?
• What current combinations are being tested and how have these preformed?
• How to mitigate toxicity risks associated with combination therapies?
• How to translate promising pre-clinical findings into clinically viable combination regimens?
Workshop F
2:30 pm Interrogating Innovative Trial Designs to Improve Patient Stratification & Streamline Clinical Progression
Synopsis
From adaptive and basket trials, to biomarker-driven approaches, innovative trial design offers promising avenues in precision oncology for RAS-driven cancers. Such enhanced trail designs require careful consideration to encompass tumor heterogeneity, resistance risks and optimal dosing strategies. With many nuances to consider, this workshop will review the recent advancements that have underscored tailored treatment approaches and question how we can improve patient stratification to pave the way for continued innovation of trial design.
This workshop will discuss:
• Where have innovative clinical trials been implemented for RAS targeting drugs? Have these been successful?
• How to balance innovation with regulatory rigor in trial design?
• How to optimize trial endpoints to capture both short-term response and long-term outcomes in the context of combination therapies?
• How to address challenges related to cross-trial comparisons