Slide 1: Preliminary Safety and Clinical Activity of Zoldonrasib (RMC-9805) in KRAS G12D NSCLC
Preliminary Safety and Clinical Activity of Zoldonrasib (RMC-9805), an Oral, RAS(ON) G12D-Selective, Tri-Complex Inhibitor in Patients with Previously Treated KRAS G12D Non-Small Cell Lung Cancer (NSCLC) Jonathan Riess*, Eric Haura, Rona Yaeger, Melissa Johnson, Jia Luo, Aparna R Parikh, Douglas Orr
Slide 2: Disclosure Information
Disclosure Information Dr. Jonathan Riess I have the following relevant financial relationships to disclose: Consultant for: Daiichi Sankyo, BMS, Janssen, Regeneron, Genentech, Merck, Pfizer, GSK, Replimmune, Oncohost, ArriVent, Nuvation, Nuvalent, Taiho Pharmaceuticals, Verastem, Boehringer Ingelhe
Slide 3: Large Unmet Need in RAS G12D Cancers
Large Unmet Need in RAS G12D Cancers Uncontrolled RAS(ON) Signaling Drives Cells to an Oncogenic State 1-3 RAS G12D Cancers are Common RAS Cancer Mutations NSCLC Normal PDAC 14% 40% CRC 38% Other 61,000 11% New patients CRC Cell Membrane with RAS G12D 15% 4 per year (U.S.) NSCLC Tightly regulated Ex
Slide 4: Zoldonrasib is an Oral, Mutant-Selective, Covalent Inhibitor Targeting RAS(ON) G12D
Zoldonrasib is an Oral, Mutant-Selective, Covalent Inhibitor Targeting the ON (Active, GTP-bound) State of RAS G12D Zoldonrasib Mechanism of Action Zoldonrasib RAS(ON) Zoldonrasib (RMC-9805) RAS(ON) Inhibitory Tri-Complexes RAS(ON) G12D-Selective RAF (RBD-CRD) • Mutant-selective covalent inhibitor o
Slide 5: Zoldonrasib Drives Deep and Durable Regressions in KRAS G12D NSCLC Preclinical Models
Zoldonrasib Drives Deep and Durable Regressions in KRAS G12D NSCLC Preclinical Models In Vivo Deep Responses in NSCLC KRAS G12D Durable Responses in NSCLC KRAS G12D Preclinical Xenograft Models Preclinical Xenograft Models 200 100 70% ORR (7/10) % Progression-Free Survival % Change from Baseline 150
Slide 6: RMC-9805-001 Phase 1 Study Design Arm A: Zoldonrasib Monotherapy
RMC-9805-001 Phase 1 Study Design Arm A: Zoldonrasib Monotherapy Key Eligibility Criteria Part 1: Dose Escalation • Advanced solid tumors with KRAS Zoldonrasib administered orally QD or BID, G12D mutations 21-day treatment cycle • Received prior standard therapy appropriate for tumor type and stage
Slide 7: Demographics and Baseline Characteristics for Patients with KRAS G12D NSCLC
Demographics and Baseline Characteristics for Patients with KRAS G12D NSCLC Treated with Zoldonrasib 1200 mg QD All treated ICI and Platinum Chemo Treated (No Prior Docetaxel) (N = 40) (N = 27) Safety Population Efficacy Population Age, years, median (range) 66 (36, 86) 65 (36, 86) Male, n (%) 17 (4
Slide 8: Treatment-Related Adverse Events for Patients with NSCLC Treated with Zoldonrasib
Treatment-Related Adverse Events (TRAEs) for Patients with KRAS G12D NSCLC Treated with Zoldonrasib 1200 mg QD All Patients with NSCLC Treated with Zoldonrasib 1200 mg PO QD (N = 40) Maximum Severity of Treatment-Related AEs Grade 1 Grade 2 Grade 3a Any Grade Any TRAE, n (%) 23 (58) 8 (20) 5 (13) 36
Slide 9: Dose Modification and Dose Intensity in Patients with KRAS G12D NSCLC
Dose Modification and Dose Intensity in Patients with KRAS G12D NSCLC Treated with Zoldonrasib 1200 mg QD All NSCLC Treated TRAEs Leading to Zoldonrasib Action Taken 1200 mg PO QD (N = 40) Dose modification, n (%) Dose interruption 6 (15) Dose reduction 1 (3) Dose discontinuation, n (%) 2 (5)a Zoldo
Slide 10: ORR and DCR in ICI and Platinum Chemo Treated Patients
ORR and DCR in Patients with KRAS G12D NSCLC Treated with Zoldonrasib 1200 mg QD ICI and Platinum Chemo Treated 100 (No Prior Docetaxel) On treatment Zoldonrasib 1200 mg PO QD (N = 27) * Unconfirmed ORRa, % (95% CI) 52 (32, 71) Best % Change in SOD from Baseline 50 DCRa, % (95% CI) 93 (76, 99) in Ta
Slide 11: Progression-Free Survival in ICI and Platinum Chemo Treated Patients
Progression-Free Survival in Patients with KRAS G12D NSCLC Treated with Zoldonrasib 1200 mg QD 100 ICI and Platinum Chemo Treated Progression-Free Survival Probability (%) 90 (No Prior Docetaxel) Zoldonrasib 1200 mg PO QD (N = 27) 80 mPFS, months (95% CI) 11.1 (5.3, NE) 70 12-month PFS, % (95% CI) 4
Slide 12: Overall Survival in ICI and Platinum Chemo Treated Patients
Overall Survival in Patients with KRAS G12D NSCLC Treated with Zoldonrasib 1200 mg QD 100 ICI and Platinum Chemo Treated 90 (No Prior Docetaxel) Zoldonrasib 1200 mg PO QD (N = 27) Overall Survival Probability (%) 80 mOS, months (95% CI) NE (NE, NE) 70 12-month OS, % (95% CI) 73 (52, 86) 60 50 40 30
Slide 13: ctDNA Molecular Response in KRAS G12D NSCLC
ctDNA Molecular Response in Patients with KRAS G12D NSCLC Treated with Zoldonrasib 1200 mg QD Zoldonrasib 1200 mg PO QD KRAS G12D VAF Zoldonrasib KRAS G12D NSCLC (N = 15) Clearance 1200 mg PO QD 100 ≥50% Clearance, 87 % (n/N) (13/15) 10 KRAS G12D VAF (%) 100% Clearance, 73 % (n/N) (11/15) 1 0.1 • 15
Slide 14: Conclusions
Conclusions Zoldonrasib (RMC-9805) is an oral, potent, mutant-selective, covalent inhibitor of RAS(ON) G12D Zoldonrasib is well tolerated and manageable with primarily Grade 1 treatment-related adverse events, no Grade 4 or 5 TRAEs, and high dose intensity Zoldonrasib has demonstrated encouraging cl
Slide 15: Acknowledgments
Acknowledgments • We thank all patients who participated in this study, their families who supported them, and the clinical investigators and research staff who cared for them • The RMC-9805-001 study is sponsored by Revolution Medicines, Inc. (ClinicalTrials.gov identifier: NCT06040541) Please scan