-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

211 Updated Results and Longer Follow-up from the AUGMENT-101 Phase 2 Study of Revumenib in All Patients with Relapsed or Refractory (R/R) KMT2Ar Acute Leukemia

Program: Oral and Poster Abstracts
Type: Oral
Session: 616. Acute Myeloid Leukemias: Investigational Drug and Cellular Therapies: Menin Inhibitors in AML
Hematology Disease Topics & Pathways:
Research, Clinical trials, Acute Myeloid Malignancies, AML, Lymphoid Leukemias, ALL, Clinical Research, Diseases, Lymphoid Malignancies, Myeloid Malignancies
Saturday, December 7, 2024: 2:00 PM

Ibrahim Aldoss, MD1, Ghayas C. Issa, MD2, James S. Blachly, MD3, Michael J. Thirman, MD4,5, Gabriel N Mannis, MD6, Martha L. Arellano, MD7, John F. DiPersio, MD, PhD8, Elie Traer, MD, PhD9, C. Michel Zwaan, Prof. Dr.10,11*, Neerav Shukla, MD12, Branko Cuglievan, MD13, Carolyn S. Grove, MBBS, FRACP, FRCPA, PhD14, Matthew Greenwood, MBBS, FRACP, FRCPA15, Christine M. McMahon, MD16, Alexander E. Perl, MD17, Richard M. Stone, MD18, Cristina Papayannidis, MD, PhD19, David S. Dickens, MD, FAAP20*, Maël Heiblig, MD, PhD21*, Andrius Žučenka, MD22,23, Pau Montesinos, PhD, MD24*, Ioannis Mantzaris, MD25, Tibor Kovacsovics, MD26*, Paul J. Shami, MD27, Li Yu, PhD28*, Rebecca G. Bagley, MA28*, Nicole McNeer, MD, PhD28* and Eytan M. Stein, MD12

1City of Hope National Medical Center, Duarte, CA
2Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
3The Ohio State University, Columbus, OH
4The University of Chicago Medicine, Chicago, IL
5Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL
6Stanford University School of Medicine, Stanford, CA
7Emory University School of Medicine, Atlanta, GA
8Washington University School of Medicine, St. Louis, MO
9Knight Cancer Institute, Oregon Health & Science University, Portland, OR
10Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands
11Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands
12Memorial Sloan Kettering Cancer Center, New York, NY
13Division of Pediatrics, MD Anderson Cancer Center, Houston, TX
14Sir Charles Gairdner Hospital, Nedlands, Australia
15Royal North Shore Hospital, Sydney, NSW, Australia
16University of Colorado School of Medicine, Denver, CO
17Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA
18Dana-Farber Cancer Institute, Boston, MA
19Institute of Hematology and Medical Oncology, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
20University of Iowa Stead Family Children's Hospital, Iowa City, IA
21Hematology, Centre Hospitalier Lyon Sud, Lyon, France
22Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
23Hematology and Oncology Department, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
24Hospital Universitari i Politècnic La Fe, Valencia, Spain
25Montefiore Einstein Comprehensive Cancer Center, Bronx, NY
26City of Hope Phoenix, Goodyear, AZ
27University of Utah Huntsman Cancer Institute, Salt Lake City, UT
28Syndax Pharmaceuticals, Inc., Waltham, MA

Background: Rearrangements of the lysine methyltransferase 2A (KMT2Ar) gene occur in ≤10% of acute leukemias (ALs) and are associated with a poor prognosis. In patients (pts) with KMT2Ar AL, the menin-KMT2A fusion protein interaction is a key driver of leukemogenesis. Revumenib, an oral, potent, and selective menin inhibitor, demonstrated a high rate of complete remission (CR) or CR with partial hematologic recovery (CR+CRh; 23%) and overall response rate (ORR; 63%) with a tolerable safety profile in pts with R/R KMT2Ar AL in the phase 2 interim analysis of AUGMENT-101 (NCT04065399). The KMT2Ar cohorts met prespecified stopping rules for efficacy, and the data from this analysis (n=57) were the basis for a New Drug Application to the FDA. Here we report longer follow-up and a larger data set, including safety and efficacy results for all pts with KMT2Ar enrolled in the phase 2 study (N=116), representing the largest evaluation of menin inhibition in pts with R/R KMT2Ar AL to date.

Methods: Pts aged ≥30 d with R/R KMT2Ar AL were enrolled and received revumenib 163 mg (95 mg/m2 if body weight <40 kg) every 12 h (q12h) with a strong CYP3A4 inhibitor azole in 28-d continuous cycles. Treatment continued until lack of at least morphological leukemia-free state (MLFS) after 4 cycles, disease progression, or unacceptable adverse events (AEs). Primary objectives were safety and tolerability and rate of CR+CRh. Key secondary endpoints included rate of composite CR (CRc [CR+CRh+CR with incomplete platelet recovery+CR with incomplete count recovery), ORR (CRc+MLFS+partial remission), and duration of response (DoR). The efficacy population included pts with centrally confirmed KMT2Ar and ≥5% baseline bone marrow blasts. Measurable residual disease (MRD) was assessed locally by flow cytometry or PCR at the discretion of investigators.

Results: At the time of the interim analysis (data cutoff [DCO]: July 24, 2023), 13 pts achieved CR+CRh (23%), 6 of whom remained in follow-up with no relapse or death at that time. In this current analysis, with 7 additional mo of follow-up (DCO: February 29, 2024), the updated median duration of CR+CRh in these 13 responders was 13.0 mo (95% CI, 3.4 mo-not reached [NR]); 5 remained in follow-up with no relapse or death, while 1 more pt had relapsed.

A total of 116 pts with R/R KMT2Ar AL received ≥1 dose of revumenib and were included in the safety population. Median age was 35.5 y (range, 0.6-75.0); 28 (24%) pts were <18 y, and 14 (12%) were ≥65 y. A total of 95 (82%) pts had AML, and 21 (18%) had ALL or MPAL; 67 (58%) were female, and 18 (16%) were non-White. Pts were heavily pretreated (median of 2 prior therapies [range, 1-11]), with 51 (44%) receiving ≥3 prior lines, 73 (63%) receiving prior venetoclax, and 59 (51%) underwent prior hematopoietic stem cell transplant (HSCT).

In the efficacy population (n=97), 22 pts (23% [95% CI, 15%-32%]) achieved CR+CRh with a median DoR of 6.4 mo (95% CI, 1.9 mo-NR). CRc rate was 42% (95% CI, 32%-53%); ORR was 64% (95% CI, 54%-73%). Of 18 CR+CRh responders with MRD results available, 11 (61%) achieved MRD negativity; 21/36 (58%) MRD-evaluable CRc responders achieved MRD negativity. Of 62 pts who achieved ORR, 21 (34%) proceeded to HSCT. Nine pts resumed revumenib post HSCT.

In the safety population (N=116), 106 (91%) pts experienced a grade ≥3 treatment-emergent AE (TEAE) and 63 (54%) experienced a grade ≥3 treatment-related AE (TRAE). The most common (≥10%) grade ≥3 TEAEs were febrile neutropenia (45 [39%]), anemia (23 [20%]), platelet count decreased (19 [16%]), differentiation syndrome (17 [15%]; only 1 grade 4, no grade 5), neutrophil count decreased (17 [15%]), white blood cell count decreased (17 [15%]), sepsis (16 [14%]), and QTc prolongation (15 [13%]; all grade 3). Sixteen pts (14%) discontinued treatment due to a TEAE, and 6 (5%) discontinued due to a TRAE. Nineteen (16%) and 4 (3%) pts experienced a TEAE or TRAE leading to death, respectively.

Conclusions: Revumenib monotherapy provides clinically meaningful responses in heavily pretreated pts with R/R KMT2Ar acute leukemias, including high rates of MRD negativity and ability to proceed to HSCT. Continued treatment and follow-up of pts after the interim analysis demonstrate the durability of ongoing response. The safety profile of revumenib with this longer follow-up is consistent with prior reports. This trial represents the largest evaluation of a targeted therapy for pts with R/R KMT2Ar acute leukemias to date.

Disclosures: Aldoss: Jazz Pharmaceuticals: Other: consulting fees; Takeda Pharmaceuticals: Other: consulting fees; Sobi: Other: consulting fees; AbbVie: Other: research support; Kite Pharma: Other: consulting fees; Pfizer: Honoraria, Other: consulting fees; Syndax Pharmaceuticals, Inc.: Other: consulting fees; Amgen: Honoraria, Other: consulting fees. Issa: Astex: Research Funding; Syndax Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees, Research Funding; Kura Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees, Research Funding; Merck: Research Funding; Celgene: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees, Research Funding; NuProbe: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees. Blachly: Syndax Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consulting fees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consulting fees. Thirman: Merck: Other: institutional funding; Nurix: Other: institutional funding; AbbVie: Honoraria, Other: institutional funding; Syndax Pharmaceuticals, Inc.: Other: institutional funding. Mannis: Gilead: Research Funding; Glycomimetics: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Forty Seven: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Membership on an entity's Board of Directors or advisory committees; Orbital Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Jazz: Research Funding; Wugen: Membership on an entity's Board of Directors or advisory committees; Astex: Research Funding; Astellas: Membership on an entity's Board of Directors or advisory committees; Aptose: Research Funding; Syndax Pharmaceuticals, Inc.: Research Funding; Immunogen: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; ImmuneOnc: Research Funding; Stemline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Macrogenics: Consultancy; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees. Arellano: Syndax Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Other: Advisory board meeting 5/31/24, Syndax pharmaceuticals, role of menin inhibition in treatment of acute leukemias. DiPersio: MacroGenics: Other: grant; Wugen: Other: grant, Patents & Royalties: royalties/licenses ; BioLineRx: Consultancy, Other: grant, consulting fees; Incyte: Other: grant; Magenta Therapeutics: Patents & Royalties: royalties/licenses ; RiverVest: Consultancy, Other: consulting fees; Vertex Pharmaceuticals: Consultancy, Other: consulting fees. Traer: Servier Laboratories: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo, Inc.: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding; Rigel Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees; Prelude Therapeutics: Research Funding; Schrödinger: Research Funding; Incyte Corporation: Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees. Zwaan: Incyte Corporation: Consultancy, Other: consulting fees; Daiichi Sankyo, Inc.: Other: institutional grant; Kura Oncology: Consultancy, Other: institutional grant, consulting fees; Bristol Myers Squibb: Consultancy, Other: consulting fees; Gilead Sciences, Inc.: Consultancy, Other: consulting fees; Astra Zeneca: Consultancy, Other: consulting fees; Beigene: Consultancy, Other: consulting fees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: institutional fees, consulting fees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: institutional fees; Innovative Therapies for Children with Cancer in Europe (ITCC) Hematologic Malignancies Committee: Other: leadership role; Chair of the Medical Research Ethics Committee (MREC) Utrecht: Other: leadership role; Jazz Pharmaceuticals: Other: institutional grant; Takeda Pharmaceuticals: Other: institutional grant; Pfizer: Other: institutional grant; AbbVie: Other: institutional grant. Shukla: Syndax Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Cuglievan: LLS: Research Funding; Octapharma: Other: travel, accommodations, research; Syndax Pharmaceuticals, Inc.: Other: travel, accommodations, Research Funding; Kura Oncology: Research Funding. Grove: Otsuka Australia Pharmaceutical: Other: institutional consultancy payment; Astellas Pharma: Other: institutional consultancy payment; institutional payment for educational event; AbbVie: Other: institutional consultancy payment. Greenwood: Servier Laboratories: Honoraria, Other: receipt of trial related materials ; Amgen: Honoraria, Other: receipt of trial related materials ; Jazz Pharmaceuticals: Honoraria. McMahon: Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Syndax Pharmaceuticals, Inc.: Research Funding; Syros Pharmaceuticals: Research Funding. Perl: ImmunoGen: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: grant, consulting fees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: grant, consulting fees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: grant, consulting fees, Research Funding; Syndax Pharmaceuticals, Inc.: Other: grant, Research Funding; Foghorn: Consultancy; Rigel Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; BeatAML, LLC: Other: DSMC member; Aptose Biosciences: Membership on an entity's Board of Directors or advisory committees; Curis: Membership on an entity's Board of Directors or advisory committees; Schrödinger,: Membership on an entity's Board of Directors or advisory committees. Stone: Aptevo Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consulting fees; AROG Pharmaceuticals: Consultancy, Other: consulting fees; AvenCell: Consultancy, Other: consulting fees; BerGenBio: Consultancy, Other: consulting fees; Bristol Myers Squibb: Consultancy, Other: consulting fees; Boston Scientific: Consultancy, Other: consulting fees; Celularity: Consultancy, Other: consulting fees; CTI BioPharma: Consultancy, Other: consulting fees; DAVA Oncology: Consultancy, Other: consulting fees; GSK: Consultancy, Other: consulting fees; Hemavant Sciences: Consultancy, Other: consulting fees; Janssen: Consultancy, Other: consulting fees; Jazz Pharmaceuticals: Consultancy, Other: consulting fees; Kura Oncology: Consultancy, Other: consulting fees; LAVA Therapeutics: Consultancy, Other: consulting fees; Ligand Pharmaceuticals: Consultancy, Other: consulting fees; Novartis: Consultancy, Other: consulting fees; Rigel Therapeutics, Inc.: Consultancy, Other: consulting fees; Syros Pharmaceuticals: Consultancy, Other: consulting fees; Syntrix Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consulting fees; Amgen: Consultancy, Other: consulting fees; Actinium Pharmaceuticals, Inc.,: Consultancy, Other: consulting fees; AbbVie: Consultancy, Other: consulting fees; Epizyme Inc: Consultancy, Other: consulting fees; Takeda Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consulting fees. Papayannidis: Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Menarini/Stemline: Honoraria; Servier: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria; Delbert Laboratories: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; GSK: Membership on an entity's Board of Directors or advisory committees; Blueprint: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Dickens: Tempus: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; YmAbs: Consultancy; American Academy of Pediatrics: Other: unpaid advocacy role; American Society of Pediatric Hematology Oncology: Other: unpaid advocacy role; Iowa Cancer Consortium: Other: unpaid advocacy role. Žučenka: Novartis: Consultancy, Honoraria, Other: travel expenses; Pfizer: Consultancy; Astellas: Consultancy, Honoraria; Johnson & Johnson: Consultancy, Honoraria, Other: travel expenses; Takeda: Other: travel expenses; AbbVie: Consultancy, Honoraria, Other: travel expenses. Montesinos: Janssen: Membership on an entity's Board of Directors or advisory committees, Other: research support, Speakers Bureau; Daiichi Sankyo, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Research Funding, Speakers Bureau; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Research Funding, Speakers Bureau; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Research Funding, Speakers Bureau; Jazzpharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Kura Oncology: Consultancy; Syndax: Consultancy; Glycomimetics: Consultancy. Kovacsovics: Astellas Pharma: Membership on an entity's Board of Directors or advisory committees; Servier Laboratories: Honoraria; Rigel Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Syndax Pharmaceuticals, Inc.: Other: institutional research support; GlycoMimetics, Inc.: Other: institutional research support; Gilead Sciences, Inc.: Other: institutional research support; Amgen: Other: institutional research support; AbbVie: Other: institutional research support; Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; NeoGenomics Laboratories: Membership on an entity's Board of Directors or advisory committees. Shami: RJH BioSciences: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences, Inc.: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo, Inc.: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Abcuro, Inc.: Other: grant; Amgen: Other: grant; Chimerix, Inc.: Other: grant; JSK Therapeutics: Other: Chief Medical Officer and serves on the Board of Directors ; National Cancer Network: Other: leadership role; US Patents: Patents & Royalties: holds US Patents (8,404,665; 9,005,656). Yu: Syndax Pharmaceuticals, Inc.: Current Employment, Other: stocks/stock options. Bagley: Syndax Pharmaceuticals, Inc.: Current Employment, Other: stocks/stock options. McNeer: Syndax Pharmaceuticals, Inc.: Current Employment, Other: stock/stock options. Stein: Jazz Pharmaceuticals: Consultancy, Other: consulting fees; Agios Pharmaceuticals: Consultancy, Other: consulting fees; Abbvie: Consultancy, Other: consulting fees; Servier: Consultancy, Other: consulting fees; Gilead: Consultancy, Other: consulting fees; Genentech: Consultancy, Other: consulting fees; AstraZeneca: Consultancy, Other: consulting fees; Celgene: Consultancy, Other: consulting fees; Astellas Pharmaceuticals: Consultancy, Other: consulting fees; Daiichi Sankyo, Inc.: Consultancy, Other: consulting fees.

Previous Abstract | Next Abstract >>
*signifies non-member of ASH