Explore the Agenda
Combination Strategies Focus Day
8:00 am Registration Opens & Morning Welcome Coffee
8:50 am Chair’s Opening Remarks
Unleashing Innovative Combinations for Targeting KRAS & Adjacent Pathways to Improve Treatment Effectiveness of RAS-Driven Cancers
9:00 am Uncovering the Potential of a KRAS G12C Inhibitor in Combination of SHP2 Inhibitor for Treatment of NSCLC
- Understanding the rationale of KRAS G12C plus SHP2 in NSCLC
- Examining the preclinical data of this combination
- Presenting the phase I/IIa results of the combination in NSCLC
9:30 am Optimizing Combination Strategies for Effective Inhibition of the MAPK Pathway in RAS-Driven Cancers
- Downstream alterations in the RAS MAPK pathway drive resistance to RAS inhibitors in the clinic
- NST-628 is a highly efficacious non-degrading pan-RAF-MEK molecular glue with broad activity in RAS-mutant cancers
- NST-628 is a promising combination anchor in KRAS-mutant cancers
10:00 am Morning Break & Networking
Optimizing RAS Inhibitor Efficacy by Creating Synergy with Other Therapies to Overcome the Immunosuppressive Tumor Microenvironment
11:00 am Farnesyl Transferase Inhibition Restores RAS Inhibitor Sensitivity in Tumors Exhibiting Innate or Adaptive Resistance
- Persistent mTORC1 activity is a frequent, nongenetic driver of inherent and adaptive resistance to RAS inhibition in KRAS-mutant preclinical models. This vulnerability is targetable with the farnesyl transferase inhibitor KO-2806, which blocks mTORC1 activation via RHEB, while sparing mTORC2 and its associated toxicities
- Across a panel of NSCLC and CRC xenograft models, KO-2806 improves tumor growth inhibition or deepens regressions induced by mutant-selective or pan-RAS inhibitors. Enhanced antitumor activity corresponds with stronger inhibition of mTORC1 signaling
- Xenograft tumors relapsing in vivo can be re-sensitized to RAS inhibition via addition of KO-2806, an effect not achievable by switching RAS inhibitor class. Farnesyl transferase inhibitors have potential as versatile RAS companion agents given their activity across tumor types, RAS inhibitor classes, and prior-treatment settings
11:30 am Panel Discussion: Identifying the Right Combination for Different Cancers by Tailoring RAS Inhibitors for Tumor-Specific Reponses
- Overcoming the complexity of tumor biology and multiple signaling pathways to select the optimal combination approach for different cancer types
- How can patient-specific genetic profiles and tumor microenvironment data inform the design of more effective combination therapies?
- How do RAS inhibitors alter the tumor microenvironment and improve response to current standard of care cancer treatments?
12:30 pm Lunch & Networking Break
Overcoming RAS Inhibitor Resistance by Leveraging Effective Combination Strategies with Immunotherapies & FAK Inhibitors to Improve Treatment Durability
1:30 pm Enhancing Anti-Tumor Immunity by Combining KRAS inhibition with Immune Checkpoint Blockade to Improve Treatment Responses
- Overcoming the immunosuppressive tumor microenvironment (TME) of KRAS-mutant tumors
- Improving understanding of the influence KRAS inhibition on tumor immune responses to increase effectiveness of immune therapies
- Exploring combination strategies to overcome challenges posed by the TME and tumor stroma
2:00 pm The FAK Inhibitor Defactinib Augments the Anti-Tumor Efficacy of the RAF/MEK Inhibitor Avutometinib for Patients with KRAS Mutant Cancers
- Scientific rationale leading to approval for patients with KRAS mutant low-grade serous ovarian cancer (LGSOC)
- Preclinical rationale and clinical update for patients with KRAS mutant PDAC and NSCLC
- Implications for FAK inhibitor combinations with the new generation of KRAS inhibitors
2:30 pm Afternoon Break & Networking
Addressing Regulatory Hurdles & Enhancing Biomarker Strategies to Accelerate Combination Therapies Towards Approval & the Patients in Need
3:00 pm Biomarker Insights & Resistance Mechanisms in KRAS G12C-Mutated mCRC: Findings from the Phase 3 CodeBreaK 300 Study
- Identify key baseline co-alterations and their impact on treatment response
- Characterize emergent alterations at progression
- Inform future combination strategies
3:30 pm Roundtable Discussion: Untangling the Regulatory Landscape Surrounding Combination Therapies to Accelerate More Innovative Treatments Towards the Patients in Need
- How to overcome the regulatory hurdles associated with combining two unapproved drugs?
- Uncovering preclinical data and safety assessments required for combining a RAS inhibitor with another approved or unapproved drug
- How do regulatory agencies assess and manage multi-drug interactions in clinical trials?
4:00 pm Continuing Sotorasib Development by Uncovering Synergistic Combination Strategies to Treat Mutated Colorectal Cancer
- Generating data in a 4% world: Doing more with less
- Highlighting considerations for design of pivotal phase 3 trial
- Uncovering a robust path to achieve regulatory approval
4:30 pm Chair’s Closing Remarks & End of Focus Day
Workshop Day
8:30 am Registration Opens & Morning Welcome Coffee
9:30 am Workshop A – Debating Pan-RAS vs Pan-KRAS Inhibitors to Achieve Good Balance Between Efficacy & Toxicity for Treating Hard-to-Target Cancers
With the field continuing to strive to find effective, durable treatments for hard-to-target cancers such as pancreatic and colorectal cancers which contain a variety of RAS mutations. This session will engage participants in a debate and explore whether pan-RAS or pan-KRAS inhibitors offer the best balance between efficacy and toxicity, gain insights into the potential of this transformative approach for targeting multiple mutations and treating more patients.
This workshop will discuss:
- How to spare targeting of wild-type HRAS and NRAS by leveraging more specific pan-KRAS inhibitors
- How to improve therapeutic benefit by broadening the scope with pan-RAS inhibitors to treat a wider population of patients
- Are the early clinical successes of pan-RAS inhibitors more promising than initially assumed, or do pan-KRAS inhibitors still hold the edge in clinical development due to their specificity?
12:30 pm Lunch Break & Networking
1:30 pm Workshop B – Unravelling Resistance Mechanisms to Uncover Non-Invasive Strategies & Reliable Biomarkers for Accurate Understanding of RASTargeting Drugs
As resistance mechanisms continue to limit the durability of RAS-targeted drugs, diving deep into these mechanisms and uncovering biomarker strategies is crucial for gaining deeper insights. Through liquid biopsy and ctDNA technologies you can discover effective biomarkers to help predict and identify resistance, enabling the development of more efficacious therapies and personalized treatment approaches.
This workshop will discuss:
- Exploring approaches to monitor and mitigate the multifaceted mechanisms underlying resistance to KRAS inhibitors for more durable treatment
- How to leverage ctDNA analysis for tracking emerging mutations and gaining insights into resistance mechanisms
- How to ensure biomarker reliability when working with heterogeneous tumors for more robust prediction and analysis