Slide 1: Distant Metastasis-Free Survival Results From the Randomized, Phase 2 mRNA-4157-P201/KEYNOTE-942 Trial
Distant Metastasis-Free Survival Results From the Randomized, Phase 2 mRNA-4157-P201/ KEYNOTE-942 Trial Adnan Khattak,1,2 Jeffrey S. Weber,3 Tarek Meniawy,4 Matthew H. Taylor,5 George Ansstas,6 Kevin B. Kim,7 Meredith McKean,8 Georgina V. Long,9 Ryan J. Sullivan,10 Mark B. Faries,11 Thuy Tran,12 C.
Slide 2: Forward Looking Statement and Disclaimer
2 Forward Looking Statement and Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: the development by Moderna and Merck of an individualized neoantigen therapy (INT)
Slide 3: Adjuvant Immune Checkpoint Inhibitor Therapy and DMFS in High-risk Melanoma
3 Adjuvant Immune Checkpoint Inhibitor Therapy and DMFS in High-risk Melanoma • Both RFS and DMFS have been evaluated as KEYNOTE-054: DMFS surrogates for overall survival. DMFS captures patients whose relapse is associated with a worse prognosis and who may need further systemic treatment1 • The KEY
Slide 4: mRNA-4157-P201/KEYNOTE-942 Study Design
4 mRNA-4157-P201/KEYNOTE-942 (NCT03897881) Study Design Randomized, phase 2, open-label study in adjuvant resected melanoma patients at high risk of recurrence Combination treatment arm: mRNA-4157 (V940) + pembrolizumab Up to 1 year of pembrolizumab treatment Primary endpoint: Key eligibility criter
Slide 5: mRNA-4157 (V940) Mechanism of Action
5 mRNA-4157 (V940) Mechanism of Action • mRNA-4157 (V940) is an individualized neoantigen therapy designed to target an individual patient’s unique tumor mutations and encodes up to 34 neoantigens1,2 • Therapies targeting neoantigens can increase endogenous neoantigen T-cell responses and induce epi
Slide 6: mRNA-4157-P201/KEYNOTE-942 Patient Demographics
6 mRNA-4157-P201/KEYNOTE-942 Patient Demographics Characteristic, n (%) mRNA-4157 (V940) + pembro (n = 107) Pembro (n = 50) Sex Male 70 (65.4) 31 (62.0) Female 37 (34.6) 19 (38.0) Age, years Mean (SD) 61.3 (13.50) 59.4 (14.25) Range (median) 63 (26-83) 61.5 (24-89) Age group <65 years 59 (55.1) 28 (
Slide 7: Primary Efficacy Endpoint: RFS
7 Primary Efficacy Endpoint: RFS1 100 + + 12-month RFS 18-month RFS + + + 83.4% + Censored ++ + 78.6% 80 +++++ + +++++++ ++ +++++ + +++++++ +++ + ++ 77.1% + +++++ + + + +++ + ++++ ++ RFS (%) 60 62.2% ++ ++++ ++ ++ ++ + 40 Events, Hazard Ratio % (n/N) (95% CI)a 20 mRNA-4157 (V940) + 22.4 (24/107) pem
Slide 8: Secondary Efficacy Endpoint: DMFS
8 Secondary Efficacy Endpoint: DMFS 18-month DMFS 100 + Censored 91.8% 80 76.8% DMFS (%) 60 40 Events, Hazard Ratio % (n/N) (95% CI)a 20 mRNA-4157 (V940) + 8.4 (9/107) pembrolizumab 0.347 (0.145-0.828) P = 0.0063 pembrolizumab 24.0 (12/50) 0 0 20 40 60 80 100 120 140 160 180 Time From First Dose of
Slide 9: Recurrence Type and Distant Recurrence Location
9 Recurrence Type and Distant Recurrence Location 24/107 (22.4%) patients in the mRNA-4157 (V940) + pembro mRNA-4157 (V940) pembro arm versus 20/50 (40.0%) in the pembro monotherapy arm + pembro (n = 50) experienced an RFS event (n = 107) Patients with distant recurrence (with or without prior recur
Slide 10: Longitudinal Pattern of DMFS Events During and After Treatment Completion
10 Longitudinal Pattern of DMFS Events During and After Treatment Completion Time From First Dose of Pembrolizumab (weeks) Reasons for death were disease progression (n = 2), unrelated AE (n = 1, without distant recurrence, from sepsis), and unknown (n = 1) in the mRNA-4157 (V940) + pembrolizumab ar
Slide 11: DMFS by ctDNA Status at Baseline
11 DMFS by ctDNA Status at Baseline 100 80 DMFS (%) 60 40 20 Time From First Dose of Pembrolizumab (weeks) + Censored 0 0 20 40 60 80 100 120 140 160 180 Number at Risk ctDNA-neg: mRNA−4157 (V940) + pembrolizumab 77 73 69 57 38 18 15 6 1 ctDNA-neg: pembrolizumab 33 30 28 26 18 7 4 0 0 ctDNA-pos: mRN
Slide 12: mRNA-4157-P201/KEYNOTE-942 Safety and Tolerability
12 mRNA-4157-P201/KEYNOTE-942 Safety and Tolerability1 mRNA-4157 (V940) + pembro (n = 104) pembro (n = 50) Event, n (%) Any grade Grade 3 Any grade Grade 3 Any AE 104 (100.0) 36 (34.6) 47 (94.0) 18 (36.0) Any treatment-related AE 104 (100.0) 26 (25.0) 41 (82.0) 9 (18.0) Serious AEa 15 (14.4) 13 (1
Slide 13: mRNA-4157-P201/KEYNOTE-942 Safety and Tolerability
13 mRNA-4157-P201/KEYNOTE-942 Safety and Tolerability All-cause immune-mediated AEs mRNA-4157 (V940) + pembro (n = 104) pembro (n = 50) Event, n (%) Any grade Grade 3a Any grade Grade 3b Any 37 (35.6) 11 (10.6) 18 (36.0) 7 (14.0) Adrenal insufficiency 5 (4.8) 4 (3.8) 2 (4.0) 1 (2.0) Colitis 6 (5.8
Slide 14: Next Steps
14 Next Steps • Additional analyses to include protocol specified RFS with ≥51 events and other subpopulation and translational assessments including immunogenicity • Longer follow-up with mRNA-4157-P201/KEYNOTE-942 to evaluate durability of the treatment effect • A phase 3 study to confirm these re
Slide 15: Conclusions
15 Conclusions • mRNA-4157 (V940) and pembrolizumab demonstrated a clinically significant improvement in RFS and DMFS compared to standard of care pembrolizumab in high-risk resected melanoma, with a 44% reduction in the risk of recurrence or death and a 65% reduction in the risk of distant metastas
Slide 16: Minimal Residual Disease by Circulating Tumor DNA as a Biomarker of Recurrence-free Survival
Minimal Residual Disease by Circulating Tumor DNA as a Biomarker of Recurrence-free Survival in Resected High-risk Melanoma Patients Treated With mRNA-4157 (V940), a Personalized Cancer Vaccine, and Pembrolizumab Matteo S. Carlino,1 Adnan Khattak,2,3 Jeffrey S. Weber,4 Tarek Meniawy,5 Ryan J. Sulliv
Slide 17: Objectives and Methods
Objectives and Methods 17 Objectives • To assess the distribution of patients with minimal residual disease (MRD) at baseline across study arms • To assess RFS (the primary study endpoint) in patient subgroups that are ctDNA-positive or ctDNA-negative at baseline • To assess the prognostic value of
Slide 18: mRNA-4157 (V940) + pembrolizumab improved RFS in ctDNA-negative patients at baseline
The combination of mRNA-4157 (V940) + pembrolizumab improved RFS in 18 ctDNA-negative patients at baseline compared to pembrolizumab monotherapy Number at risk ctDNA-neg: mRNA (V940) + pembrolizumab 77 72 69 57 38 18 15 6 1 ctDNA-neg: pembrolizumab 33 29 27 25 17 6 4 0 0 ctDNA-pos: mRNA (V940) + pem
Slide 19: ctDNA status at baseline had notable negative prognostic value
Assessments of the association of various biomarkers with RFS across 19 study arms suggested that ctDNA status at baseline had notable negative prognostic value Distribution of ctDNA-positive and ctDNA-negative Patients Across Study Arms mRNA-4157 (V940) ctDNA, + pembrolizumab Pembrolizumab Total n
Slide 20: Acknowledgments
20 Acknowledgments Thank you to the following groups who made this trial possible: • The patients and their families, along with all of the site staff • The personnel at all of our vendors and collaborators • The scientists, regulatory, operations, and manufacturing teams who discovered, improved, a
Slide 21: Thank You
THANK YOU
Slide 22: Appendix
Appendix
Slide 23: ctDNA in Cancer Detection
ctDNA in Cancer Detection What Is ctDNA and How is it Collected? • Tumor-derived circulating DNA (ctDNA) are cell free short nucleic fragments released by tumor cell apoptosis and/or necrosis1 • ctDNA in the blood may be obtained by a minimally invasive liquid biopsy2,3 Blood vessel CTC LIQUID BIOPS
Slide 24: Using ctDNA to Measure Minimal Residual Disease (MRD)
Using ctDNA to Measure Minimal Residual Disease (MRD) What MRD? • Minimal residual disease (MRD) refers to a small number of malignant cells that remain following primary treatment that are capable of causing recurrent disease1 • MRD is a significant prognostic indicator that may help predict recurr