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MOMENTUM: PHASE 3 RANDOMIZED STUDY OF MOMELOTINIB (MMB) VERSUS DANAZOL (DAN) IN SYMPTOMATIC AND ANEMIC MYELOFIBROSIS (MF) PATIENTS PREVIOUSLY TREATED WITH A JAK INHIBITOR
Author(s): ,
Srdan Verstovsek
Affiliations:
The University of Texas MD Anderson Cancer Center, Houston, TX,États-unis;The University of Texas MD Anderson Cancer Center, Houston, TX,Vereinigte Staaten;The University of Texas MD Anderson Cancer Center, Houston, TX,Stati Uniti;The University of Texas MD Anderson Cancer Center, Houston, TX,United States;The University of Texas MD Anderson Cancer Center, Houston, TX,Estados Unidos;The University
,
Alessandro Vannucchi
Affiliations:
Center Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence,Florence,Italie;Center Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence,Florence,Italien;Center Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence,Florence,Italia;Center Research and Innovation of Myeloproliferativ
,
Aaron Gerds
Affiliations:
Cleveland Clinic Department of Hematology and Medical Oncology, Avon, OH,États-unis;Cleveland Clinic Department of Hematology and Medical Oncology, Avon, OH,Vereinigte Staaten;Cleveland Clinic Department of Hematology and Medical Oncology, Avon, OH,Stati Uniti;Cleveland Clinic Department of Hematology and Medical Oncology, Avon, OH,United States;Cleveland Clinic Department of Hematology and Medica
,
Haifa Kathrin Al-Ali
Affiliations:
University Hospital of Halle,Halle,Allemagne;University Hospital of Halle,Halle,Deutschland;University Hospital of Halle,Halle,Germania;University Hospital of Halle,Halle,Germany;University Hospital of Halle,Halle,Alemania;University Hospital of Halle,Halle,Duitsland;University Hospital of Halle,Halle,Alemanha;University Hospital of Halle,Halle,Германия;University Hospital of Halle,Halle,Tyskland
,
David Lavie
Affiliations:
Hadassah Hebrew University Medical Center,Jerusalem ,Israël;Hadassah Hebrew University Medical Center,Jerusalem ,Israel;Hadassah Hebrew University Medical Center,Jerusalem ,Israele;Hadassah Hebrew University Medical Center,Jerusalem ,Israel;Hadassah Hebrew University Medical Center,Jerusalem ,Israel;Hadassah Hebrew University Medical Center,Jerusalem ,Israel;Hadassah Hebrew University Medical Cent
,
Andrew Kuykendall
Affiliations:
Moffitt Cancer Center,Tampa, FL,États-unis;Moffitt Cancer Center,Tampa, FL,Vereinigte Staaten;Moffitt Cancer Center,Tampa, FL,Stati Uniti;Moffitt Cancer Center,Tampa, FL,United States;Moffitt Cancer Center,Tampa, FL,Estados Unidos;Moffitt Cancer Center,Tampa, FL,Verenigde Staten;Moffitt Cancer Center,Tampa, FL,Estados Unidos;Moffitt Cancer Center,Tampa, FL,United States;Moffitt Cancer Center,Tampa
,
Sebastian Grosicki
Affiliations:
Medical University of Silesia , Katowice,Pologne;Medical University of Silesia , Katowice,Polen;Medical University of Silesia , Katowice,Polonia;Medical University of Silesia , Katowice,Poland;Medical University of Silesia , Katowice,Polonia;Medical University of Silesia , Katowice,Polen;Medical University of Silesia , Katowice,Polonia;Medical University of Silesia , Katowice,Польша;Medical Univer
,
Alessandra Iurlo
Affiliations:
Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico,Milan,Italie;Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico,Milan,Italien;Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico,Milan,Italia;Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico,Milan,Italy;Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico,Milan,Italia;Foundation IRCCS Ca' Granda Ospedale Maggiore
,
Yeow Tee Goh
Affiliations:
Singapore General Hospital,Singapore,Singapour;Singapore General Hospital,Singapore,Singapur;Singapore General Hospital,Singapore,Singapore;Singapore General Hospital,Singapore,新加坡;Singapore General Hospital,Singapore,Singapur;Singapore General Hospital,Singapore,Singapore;Singapore General Hospital,Singapore,Singapura;Singapore General Hospital,Singapore,Сингапур;Singapore General Hospital,Singap
,
Mihaela Lazaroiu
Affiliations:
Policlinica de Diagnostic Rapid Brasov,Brasov,Roumanie;Policlinica de Diagnostic Rapid Brasov,Brasov,Rumänien;Policlinica de Diagnostic Rapid Brasov,Brasov,Romania;Policlinica de Diagnostic Rapid Brasov,Brasov,罗马尼亚;Policlinica de Diagnostic Rapid Brasov,Brasov,Rumania;Policlinica de Diagnostic Rapid Brasov,Brasov,Roemenië;Policlinica de Diagnostic Rapid Brasov,Brasov,Romênia;Policlinica de Diagnos
,
Miklos Egyed
Affiliations:
Somogy County Mór Kaposi General Hospital,Kaposvár,Hongrie;Somogy County Mór Kaposi General Hospital,Kaposvár,Ungarn;Somogy County Mór Kaposi General Hospital,Kaposvár,Ungheria;Somogy County Mór Kaposi General Hospital,Kaposvár,Hungary;Somogy County Mór Kaposi General Hospital,Kaposvár,Hungría;Somogy County Mór Kaposi General Hospital,Kaposvár,Hongarije;Somogy County Mór Kaposi General Hospital,Ka
,
Maria Laura Fox
Affiliations:
Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus,Barcelona,Espagne;Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus,Barcelona,Spanien;Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus,B
,
Donal McLornan
Affiliations:
Guy's and Saint Thomas' NHS Foundation Trust,London,Royaume-uni;Guy's and Saint Thomas' NHS Foundation Trust,London,Vereinigtes Königreich;Guy's and Saint Thomas' NHS Foundation Trust,London,Regno Unito;Guy's and Saint Thomas' NHS Foundation Trust,London,United Kingdom;Guy's and Saint Thomas' NHS Foundation Trust,London,Reino Unido;Guy's and Saint Thomas' NHS Foundation Trust,London,Verenigd Konin
,
Andrew Perkins
Affiliations:
Monash University,Melbourne,Australie;Monash University,Melbourne,Australien;Monash University,Melbourne,Australia;Monash University,Melbourne,Australia;Monash University,Melbourne,Australia;Monash University,Melbourne,Australië;Monash University,Melbourne,Austrália;Monash University,Melbourne,Австралия;Monash University,Melbourne,Australien
,
Sung-Soo Yoon
Affiliations:
Seoul National University Hospital,Seoul,Corée, République De;Seoul National University Hospital,Seoul,Corea del Sud;Seoul National University Hospital,Seoul,South Korea,Republic;Seoul National University Hospital,Seoul,Zuid Korea;Seoul National University Hospital,Seoul,República da Korea;Seoul National University Hospital,Seoul,Корея, южная
,
Vikas Gupta
Affiliations:
Princess Margaret Cancer Centre, Toronto, ON,Canada;Princess Margaret Cancer Centre, Toronto, ON,Kanada;Princess Margaret Cancer Centre, Toronto, ON,Canada;Princess Margaret Cancer Centre, Toronto, ON,Canada;Princess Margaret Cancer Centre, Toronto, ON,Canadá;Princess Margaret Cancer Centre, Toronto, ON,Canada;Princess Margaret Cancer Centre, Toronto, ON,Canadá;Princess Margaret Cancer Centre, Tor
,
Jean-Jacques Kiladjian
Affiliations:
Saint-Louis Hospital (AP-HP),Paris,France;Saint-Louis Hospital (AP-HP),Paris,Frankreich;Saint-Louis Hospital (AP-HP),Paris,Francia;Saint-Louis Hospital (AP-HP),Paris,France;Saint-Louis Hospital (AP-HP),Paris,Francia;Saint-Louis Hospital (AP-HP),Paris,Frankrijk;Saint-Louis Hospital (AP-HP),Paris,França;Saint-Louis Hospital (AP-HP),Paris,Франция ;Saint-Louis Hospital (AP-HP),Paris,Frankrike
,
Rafe Donahue
Affiliations:
Sierra Oncology, Inc.,San Mateo, CA,États-unis;Sierra Oncology, Inc.,San Mateo, CA,Vereinigte Staaten;Sierra Oncology, Inc.,San Mateo, CA,Stati Uniti;Sierra Oncology, Inc.,San Mateo, CA,United States;Sierra Oncology, Inc.,San Mateo, CA,Estados Unidos;Sierra Oncology, Inc.,San Mateo, CA,Verenigde Staten;Sierra Oncology, Inc.,San Mateo, CA,Estados Unidos;Sierra Oncology, Inc.,San Mateo, CA,United St
,
Jun Kawashima
Affiliations:
Sierra Oncology, Inc.,San Mateo, CA,États-unis;Sierra Oncology, Inc.,San Mateo, CA,Vereinigte Staaten;Sierra Oncology, Inc.,San Mateo, CA,Stati Uniti;Sierra Oncology, Inc.,San Mateo, CA,United States;Sierra Oncology, Inc.,San Mateo, CA,Estados Unidos;Sierra Oncology, Inc.,San Mateo, CA,Verenigde Staten;Sierra Oncology, Inc.,San Mateo, CA,Estados Unidos;Sierra Oncology, Inc.,San Mateo, CA,United St
Ruben Mesa
Affiliations:
UT Health San Antonio Cancer Center,San Antonio, TX,États-unis;UT Health San Antonio Cancer Center,San Antonio, TX,Vereinigte Staaten;UT Health San Antonio Cancer Center,San Antonio, TX,Stati Uniti;UT Health San Antonio Cancer Center,San Antonio, TX,United States;UT Health San Antonio Cancer Center,San Antonio, TX,Estados Unidos;UT Health San Antonio Cancer Center,San Antonio, TX,Verenigde Staten;
(Abstract release date: 05/12/22) EHA Library. Verstovsek S. 06/11/22; 357059; S195
Dr. Srdan Verstovsek
Dr. Srdan Verstovsek
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S195

Type: Oral Presentation

Session title: Treatments and complications in MPN

Background
MMB, a novel oral ACVR1/ALK2 and JAK1/2 inhibitor, showed clinical activity on MF symptoms, red blood cell (RBC) transfusion requirements (anemia), and spleen volume in the SIMPLIFY trials. 

Aims
This pivotal phase 3 study of MF patients (pts) previously treated with a JAK inhibitor (JAKi) tested MMB vs DAN on key symptom, anemia, and spleen volume endpoints at 24 weeks (wks).

Methods
Eligibility: Primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; MF Symptom Assessment Form Total Symptom Score (MFSAF TSS) ≥10; hemoglobin (Hgb) <10 g/dL; prior JAKi for ≥90 days, or ≥28 days if RBC transfusions ≥4 units in 8 wks or Gr 3/4 thrombocytopenia, anemia, or hematoma; palpable spleen ≥5 cm. Stratification: TSS (≥22 vs <22), palpable spleen (≥12 cm vs <12 cm), and RBC units transfused (0, 1-4, and 5+). JAKi taper and washout was ≥21 days. Randomization: 2:1 to MMB 200 mg QD plus DAN placebo or DAN 600 mg QD plus MMB placebo for 24 wks, after which pts could receive open-label MMB. Assessments: Pt reported symptoms using a daily eDiary and spleen volume by MRI or CT. The primary endpoint was TSS response (≥50% reduction from baseline [BL]) rate at wk 24. Secondary endpoints, assessed sequentially at wk 24, were RBC transfusion independence (TI) rate, splenic response rate (SRR; ≥25% reduction in volume from BL), change from BL in TSS, SRR (≥35% reduction from BL) and rate of zero transfusions since BL. Informed consent was obtained from all participants.

Results
94 of 130 (72%) MMB pts and 38 of 65 (58%) DAN pts completed the 24-wk randomized treatment (RT) phase. Median BL TSS were 28 (MMB) and 26 (DAN), Hgb were 8.1 (MMB) and 7.9 (DAN) g/dL, and platelets were 97 (MMB) and 94 (DAN) x109/L. BL TI was 13% (MMB) and 15% (DAN). BL mean spleen volume was 2367 (MMB) and 2288 (DAN) cm3. Prior JAKi was ruxolitinib in 195 pts (100%) and fedratinib in 9 pts (5%); mean duration of prior JAKi was 134 weeks. All primary and key secondary endpoints were met (Table). Most common Gr ≥3 treatment-emergent adverse events (TEAEs) in the RT phase of the study were thrombocytopenia (MMB, 22%; DAN, 12%) and anemia (MMB, 8%; DAN, 11%). Gr ≥3 infections occurred in 15% of MMB and 17% of DAN pts. Peripheral neuropathy (PN) occurred in 5 (4%) of MMB (all Gr ≤2) and 1 (2%) of DAN (Gr ≤2) pts in the RT phase, and none discontinued study drug due to PN. Overall, TEAEs led to study drug discontinuation in 18% of MMB and 23% of DAN pts, and serious TEAEs were reported in 35% of MMB and 40% of DAN pts, in RT phase. A trend toward improved OS up to wk 24 was seen with MMB vs DAN (HR=0.506, p=0.0719).

Conclusion
In symptomatic and anemic MF pts, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival. MMB may address a critical unmet need, particularly in MF pts with anemia. NCT04173494.

Keyword(s): Clinical trial, Janus Kinase inhibitor, Myelofibrosis, Phase III

Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S195

Type: Oral Presentation

Session title: Treatments and complications in MPN

Background
MMB, a novel oral ACVR1/ALK2 and JAK1/2 inhibitor, showed clinical activity on MF symptoms, red blood cell (RBC) transfusion requirements (anemia), and spleen volume in the SIMPLIFY trials. 

Aims
This pivotal phase 3 study of MF patients (pts) previously treated with a JAK inhibitor (JAKi) tested MMB vs DAN on key symptom, anemia, and spleen volume endpoints at 24 weeks (wks).

Methods
Eligibility: Primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; MF Symptom Assessment Form Total Symptom Score (MFSAF TSS) ≥10; hemoglobin (Hgb) <10 g/dL; prior JAKi for ≥90 days, or ≥28 days if RBC transfusions ≥4 units in 8 wks or Gr 3/4 thrombocytopenia, anemia, or hematoma; palpable spleen ≥5 cm. Stratification: TSS (≥22 vs <22), palpable spleen (≥12 cm vs <12 cm), and RBC units transfused (0, 1-4, and 5+). JAKi taper and washout was ≥21 days. Randomization: 2:1 to MMB 200 mg QD plus DAN placebo or DAN 600 mg QD plus MMB placebo for 24 wks, after which pts could receive open-label MMB. Assessments: Pt reported symptoms using a daily eDiary and spleen volume by MRI or CT. The primary endpoint was TSS response (≥50% reduction from baseline [BL]) rate at wk 24. Secondary endpoints, assessed sequentially at wk 24, were RBC transfusion independence (TI) rate, splenic response rate (SRR; ≥25% reduction in volume from BL), change from BL in TSS, SRR (≥35% reduction from BL) and rate of zero transfusions since BL. Informed consent was obtained from all participants.

Results
94 of 130 (72%) MMB pts and 38 of 65 (58%) DAN pts completed the 24-wk randomized treatment (RT) phase. Median BL TSS were 28 (MMB) and 26 (DAN), Hgb were 8.1 (MMB) and 7.9 (DAN) g/dL, and platelets were 97 (MMB) and 94 (DAN) x109/L. BL TI was 13% (MMB) and 15% (DAN). BL mean spleen volume was 2367 (MMB) and 2288 (DAN) cm3. Prior JAKi was ruxolitinib in 195 pts (100%) and fedratinib in 9 pts (5%); mean duration of prior JAKi was 134 weeks. All primary and key secondary endpoints were met (Table). Most common Gr ≥3 treatment-emergent adverse events (TEAEs) in the RT phase of the study were thrombocytopenia (MMB, 22%; DAN, 12%) and anemia (MMB, 8%; DAN, 11%). Gr ≥3 infections occurred in 15% of MMB and 17% of DAN pts. Peripheral neuropathy (PN) occurred in 5 (4%) of MMB (all Gr ≤2) and 1 (2%) of DAN (Gr ≤2) pts in the RT phase, and none discontinued study drug due to PN. Overall, TEAEs led to study drug discontinuation in 18% of MMB and 23% of DAN pts, and serious TEAEs were reported in 35% of MMB and 40% of DAN pts, in RT phase. A trend toward improved OS up to wk 24 was seen with MMB vs DAN (HR=0.506, p=0.0719).

Conclusion
In symptomatic and anemic MF pts, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival. MMB may address a critical unmet need, particularly in MF pts with anemia. NCT04173494.

Keyword(s): Clinical trial, Janus Kinase inhibitor, Myelofibrosis, Phase III

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