Revolution Medicines, Inc. · NASDAQ:RVMD
Revolution Medicines — ESMO 2023
16 slides from Revolution Medicines's conference presentation, October 2023
Slide 1: Preliminary Clinical Activity of RMC-6236 in KRAS-Mutant PDAC and NSCLC
Preliminary Clinical Activity of RMC-6236, a First-in-Class, RAS-Selective, Tri-Complex RASMULTI(ON) Inhibitor in Patients with KRAS-Mutant Pancreatic Ductal Adenocarcinoma (PDAC) and Non-Small Cell Lung Cancer (NSCLC) Kathryn C. Arbour1, Salman Punekar2, Ignacio Garrido-Laguna3, David S. Hong4, Bri
Slide 2: Declaration of Interests
Declaration of Interests Kathryn C. Arbour Consulting: Amgen, Novartis, G1 Therapeutics, AstraZeneca, and Sanofi-Genzyme Research funding to institution: Genentech (local PI), Mirati Therapeutics (local PI), Revolution Medicines (local PI) Kathryn C. Arbour, MD Content of this presentation is copyri
Slide 3: RMC-6236 is a First-in-Class, RAS(ON) Inhibitor
RMC-6236 is a First-in-Class, RASMULTI(ON) Inhibitor • RMC-6236 is a novel, oral, non-covalent RASMULTI(ON) inhibitor that is selective for the active, GTP-bound or ON state of both mutant and wild-type variants of the canonical RAS isoforms • Preclinical studies have demonstrated deep and sustained
Slide 4: RMC-6236-001 Phase 1 Study Design
RMC-6236-001 Phase 1 Study Design Key Eligibility Criteria Dose Escalation • Advanced solid tumors RMC-6236 administered orally QD, with KRASG12X mutations 21-day treatment cycle (currently excluding KRASG12C) 500 mg • Received prior standard 400 mg Dose therapy appropriate for 300 mg Expansion / tu
Slide 5: Patient Demographics and Baseline Characteristics
Patient Demographics and Baseline Characteristics NSCLCa PDACa N = 46 N = 65 Age, median (range), years 65 (31–83) 64 (30–86) NSCLC Female, n (%) 25 (54) 31 (48) G12D G12V ECOG PS, n (%) 20 (44) 19 (41) KRAS mutation 0 11 (24) 20 (31) n, (%) 1 35 (76) 45 (69) Smoking status, n (%) Current 2 (4) 2 (3
Slide 6: Summary of Treatment-Related Adverse Events
Summary of Treatment-Related Adverse Events Patients with NSCLC and PDAC Treated at ≥80 mg QD (N = 111) Maximum severity of treatment-related AEs Grade 1 Grade 2 Grade 3 Grade 4 Any Grade TRAEs occurring in ≥10% of patients, n (%) Rasha 58 (52) 25 (23) 7 (6) 0 90 (81) Nausea 40 (36) 11 (10) 0 0 51 (
Slide 7: KRAS G12X NSCLC: Best Response
KRASG12X NSCLC: Best Response Tumor Response Evaluable for Efficacy (N = 40)a (per RECIST 1.1) Best % Change from Baseline in Target Lesion Best overall response, n (%) CR 1 (3) PR 14 (35) SD 19 (48) PD 5 (13) NE b 1 (3) ORR, n (%) 15 (38) Confirmed, n 12 DCR (CR+PR+SD), 34 (85) n (%) *Unconfirmed P
Slide 8: KRAS G12X NSCLC: Duration of Treatment and Responses
KRASG12X NSCLC: Duration of Treatment and Responses D Evaluable for Efficacy (N = 40)a V D D V D S Patients with KRASG12X Mutation V D V Median time to response: 1.4 months V V V (range, 1.2–2.7 months) V D V D D Median time on treatment: 3.1 months D D A (range, 0.5–10.9 months) D V V V V D D D D V
Slide 9: Case Report: Patient with KRAS G12V NSCLC
Case Report: Patient with KRASG12V NSCLC Demographics and Baseline Baseline On-Treatment, Week 6 Characteristics • 83-year-old woman • Former smoker (~60 pack years) • Diagnosed with NSCLC in 2021 Treatment History • Prior therapies: • Ipilimumab/nivolumab • Paclitaxel • Carboplatin/pemetrexed Targe
Slide 10: KRAS G12X PDAC: Best Response
KRASG12X PDAC: Best Response Tumor Response Evaluable for Efficacy (N = 46)a (per RECIST 1.1) Best % Change from Baseline in Target Lesion Best overall response, n (%) PR 9 (20) SD 31 (67) PD 3 (7) NEb 3 (7) ORR, n (%) 9 (20) Confirmed, n 5 DCR (CR+PR+SD), 40 (87) n (%) *Unconfirmed PR per RECIST 1.
Slide 11: KRAS G12X PDAC: Duration of Treatment and Responses
KRASG12X PDAC: Duration of Treatment and Responses Evaluable for Efficacy (N = 46)a D D V D D D R Patients with KRASG12X Mutation D V D D Median time to response: 1.4 months D V R (range, 1.2–4.1 months) V D D S R R Median time on treatment: 3.3 months D V V (range, 0.2–10.9 months) D V R R R R D D
Slide 12: Case Report: Patient with KRAS G12R PDAC
Case Report: Patient with KRASG12R PDAC Demographics and Baseline Baseline On-Treatment, Week 12 Characteristics • 57-year-old man • Diagnosed with PDAC in 2022 Treatment History • Prior therapies • Gemcitabine/nab-paclitaxel/ canakinumab/spartalizumab • FOLFIRINOX RMC-6236 Treatment Course Target L
Slide 13: KRAS Variant Allele Frequency in ctDNA and Clinical Response
KRAS Variant Allele Frequency in ctDNA Across Tumor Types and Correlation with Clinical Response PR/PR* SD PD 100.0 NSCLC • Patients with NSCLC or PDAC were dosed KRASG12X VAF Percent PDAC at 80–300 mg 10.0 • Overall, 23/50 patients (46%) were evaluable for change in mutant KRAS VAF while on-treatme
Slide 14: Conclusions
Conclusions • RMC-6236 is an oral, first-in-class, RAS-selective, RASMULTI(ON) inhibitor. • At clinically active doses, RMC-6236 was generally well tolerated. • RMC-6236 demonstrated encouraging anti-tumor activity in patients with previously treated NSCLC and PDAC across several dose levels and KRA
Slide 15: Acknowledgements
Acknowledgements • We thank all the patients who participated in this study, their families who supported them, and the clinical investigators and research staff who cared for them. • This study is sponsored by Revolution Medicines, Inc. (ClinicalTrials.gov identifier: NCT05379985). Virginia San Ant
Slide 16: European Society for Medical Oncology (ESMO)
European Society for Medical Oncology (ESMO) Via Ginevra 4, CH-6900 Lugano T. +41 (0)91 973 19 00 esmo@esmo.org esmo.org 16