Slide 1: Ziftomenib combined with intensive induction chemotherapy (7+3) in newly diagnosed NPM1-m or KMT2A-r AML
Ziftomenib combined with intensive induction S136 chemotherapy (7+3) in newly diagnosed NPM1-m or KMT2A-r acute myeloid leukemia: Updated phase 1a/b results from KOMET-007 Harry Erba1, Eunice S. Wang2, Amir T. Fathi3, Gail J. Roboz4, Yazan F. Madanat5, Stephen A. Strickland6, Suresh Balasubramanian7
Slide 2: Presenter Disclosures
Presenter Disclosures Agios (Leadership, Consulting/Advisory, Speakers’ Bureau, Institutional Research Funding); AbbVie (Honoraria, Consulting/Advi sory, Institutional Research Funding, Chair of Independent Review Committee for VIALE A and VIALE C); Stemline (Consulting/Advisory); Servier (Consultin
Slide 3: Ziftomenib Targets the Menin Pathway, a Foundational Target in AML
Ziftomenib Targets the Menin Pathway, a Foundational Target in AML • NPM1-m and KMT2A-r drive leukemogenesis in ~35–40% of AML1,2 • Ziftomenib is a potent, highly selective, oral, investigational menin inhibitor with clinical activity as both monotherapy and in combination for adults with NPM1-m or
Slide 4: KOMET-007: Ongoing Combination Trial of Ziftomenib in Newly Diagnosed AML
KOMET-007: Ongoing Combination Trial of Ziftomenib in Newly Diagnosed AML Ziftomenib / 7+3 Combination Adult AML with Phase 1a: High-Riska AML Phase 1b: All IC-eligible AML NPM1-m or KMT2A-r Dose Escalation Dose Expansion / RP2D Determination enroll independently Dose Selection RP2D Validation: Zift
Slide 5: KOMET-007 in 1L AML: Safety & Efficacy Populations
KOMET-007 in 1L AML: Safety & Efficacy Populations ITT (Safety) Population: 82 Enrolled and treated with Ziftomenib 600 mg / 7+3 combination 49 NPM1-m 33 KMT2A-r 5 NPM1-m – no response 6 KMT2A-r – no response assessment as of data assessment as of data cut cut Response-Evaluablea (Efficacy) Populati
Slide 6: Baseline Characteristics and Disposition: 1L AML (N=82)
Baseline Characteristics and Disposition: 1L AML (N=82) NPM1-m KMT2A-r All Patients 600 mg 600 mg 600 mg (n=49) (n=33) (N=82) Median age, years (range) 60 (30–71) 43 (18–70) 56 (18–71) Female, n (%) 25 (51) 18 (55) 43 (52) Race, n (%) White 35 (71) 20 (61) 55 (67) Non-White 14 (29) 13 (39) 27 (33) E
Slide 7: Safety and Tolerability of Ziftomenib in Combination with 7+3 in 1L AML (N=82)
Safety and Tolerability of Ziftomenib in Combination with 7+3 in 1L AML (N=82) TEAEs in ≥25% of All Patients NPM1-m KMT2A-r All Patients 600 mg 600 mg 600 mg n (%) (n=49) (n=33) (N=82) Any Grade 46 (94) 31 (94) 77 (94) Febrile neutropenia 26 (53) 23 (70) 49 (60) Diarrhea 22 (45) 17 (52) 39 (48) Plat
Slide 8: Safety and Tolerability: Grade ≥3 TEAEs and Ziftomenib-related Events
Safety and Tolerability of Ziftomenib in Combination with 7+3 in 1L AML (N=82) Grade ≥3 TEAEs in ≥10% of All Patients NPM1-m KMT2A-r All Patients 600 mg 600 mg 600 mg n (%) (n=49) (n=33) (N=82) Grade ≥3 42 (86) 29 (88) 71 (87) Febrile neutropenia 25 (51) 20 (61) 45 (55) Platelet count decreased 23 (
Slide 9: Clinical Activity in All Response-Evaluable 1L Patients (N=71)
Clinical Activity in All Response-Evaluablea 1L Patients (N=71) NPM1-m KMT2A-r All Patients 600 mg 600 mg 600 mg n (%) (n=44) (n=27) (N=71) CRc 41 (93) 24 (89) 65 (92) ORR 43 (98) 24 (89) 67 (94) CR 37 (84) 20 (74) 57 (80) CRh 1 (2) 0 1 (1) CRi 3 (7) 4 (15) 7 (10) MLFS 2 (5) 0 2 (3) PR 0 0 0 NR 1 (2
Slide 10: Duration of Treatment & Preliminary Clinical Outcomes in NPM1-m 1L AML
Duration of Treatment & Preliminary Clinical Outcomes in NPM1-m 1L AML For NPM1-m, after a median follow-up of 24.9 weeks (range 4.3–47.1): - Median duration of CR was not reacheda - Median OS was not reacheda - 2 NPM1-m patients received HSCT - 3 Discontinuations due to relapse - 96% (47/49) of pat
Slide 11: Duration of Treatment & Preliminary Clinical Outcomes in KMT2A-r 1L AML
Duration of Treatment & Preliminary Clinical Outcomes in KMT2A-r 1L AML For KMT2A-r, after a median follow-up of 15.7 weeks (range 1.1–40.3): - Median duration of CR: 25.6 weeks (95% CI 8.3–not estimable)a and follow-up continues - Median OS was not reacheda - 6 KMT2A-r patients received HSCT. Thus
Slide 12: Neutrophil and Platelet Recovery in CRc Responders: 1L AML
Neutrophil and Platelet Recovery in CRc Responders: 1L AML NPM1-m KMT2A-r All Patients 600 mg 600 mg 600 mg Median days (range), Cycle 1 (n=41) (n=24) (n=65) ANC ≥0.5 × 109/L 28 (19–66) 32 (20–63) 31 (19–66) ANC ≥1.0 × 109/L 30.5 (20–88) 33 (20–63) 32 (20–88) Platelets ≥50 × 109/L 27 (18–105) 31.5 (
Slide 13: Conclusions
Conclusions • In the ongoing KOMET-007 study, ziftomenib 600 mg QD combined with 7+3 was well tolerated, with a safety profile consistent with previous reports - Low rates of ziftomenib-related cytopenia and no additional myelosuppression observed with the combination - Ziftomenib 600 mg QD did not
Slide 14: KOMET-017: Phase 3 Ziftomenib Pivotal 1L Combination Studies
KOMET-017: Phase 3 Ziftomenib Pivotal 1L Combination Studies • Two independently KOMET-017-NIC: Non-intensive therapy – Ziftomenib + venetoclax/azacitidine combo powered, Patients Arm A Ziftomenib Primary endpoints registration-enabling, • NPM1-m AML R Venetoclax + Azacitidine • CR 1:1 randomized ph
Slide 15: Acknowledgements
Acknowledgements • The patients, their families, and their caregivers • KOMET-007 study investigators and their study teams • This study was sponsored by Kura Oncology, Inc., in partnership with Kyowa Kirin Group • Medical writing support was provided by Oxford PharmaGenesis, Inc., with funding from