Essential ThrombocythemiaPhase 3EXCALIBUR-ET2NCT07623200
A Phase 3 Study of INCA033989 Versus Best Available Therapy in Participants With Essential Thrombocythemia
A Phase 3 study testing INCA033989 and Best Available Treatment in people with Essential Thrombocythemia, run by Incyte Corporation at 178 sites in 19 countries.
Trial summary
This study is being conducted to evaluate INCA033989 versus best available therapy in participants with essential thrombocythemia and a CALR mutation previously treated with cytoreductive therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Essential Thrombocythemia
- What is being tested?
- INCA033989 and Best Available Treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 426 participants
- Where
- 178 sitesin 19 countries
- Study dates
- 8 Sep 2026to 1 Nov 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of high-risk ET.
- Presence of mutCALR.
- Prior treatment with at least 1 cytoreductive therapy.
Who cannot join
- Presence of any hematologic malignancy other than ET.
- Major bleeding or thrombosis within the last 3 months prior to study enrollment.
- Any prior allogenic or autologous stem-cell transplantation.
- Unresolved toxicity ≥ Grade 2 from previous therapy except for stable chronic toxicities (Grade 2) not expected to resolve, such as stable Grade 2 peripheral neuropathy.
- Prior nonhematologic malignancy except for the following: Malignancy treated with curative intent and with no evidence of active disease for more than 2 years before screening. Adequately treated carcinoma in situ without current evidence of disease.
- Other protocol-defined Inclusion/Exclusion Criteria apply.
Trial locations and contacts
178 sites in 19 countries. Contact the study team or a site near you to ask about taking part.
178 sites in 19 countries
United States42 sites, 42 recruiting
- Not yet recruiting
University of Michigan Rogel Cancer Center Adult Bone Marrow Transplant Clinic
Ann Arbor, Michigan, 48109-4000
- Not yet recruiting
Johns Hopkins Medicine-the Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231
- Not yet recruiting
Our Lady of the Lake Medical Center
Baton Rouge, Louisiana, 70808
- Not yet recruiting
University of Alabama At Birmingham Comprehensive Cancer Center
Birmingham, Alabama, 35205
- Not yet recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
- Not yet recruiting
Beth Israel Deaconess Medical Center (Bidmc)
Boston, Massachusetts, 02215
- Not yet recruiting
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, 60611
- Not yet recruiting
University of Chicago
Chicago, Illinois, 60637
- Not yet recruiting
Cleveland Clinic Taussig Cancer Ctr
Cleveland, Ohio, 44195
- Not yet recruiting
Maryland Oncology Hematology, P.A.
Columbia, Maryland, 21044
- Not yet recruiting
Missouri Cancer Associates
Columbia, Missouri, 65201
- Not yet recruiting
Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
- Recruiting
City of Hope Medical Center
Duarte, California, 91010
- Not yet recruiting
Duke University Medical Center
Durham, North Carolina, 27705
- Not yet recruiting
Willamette Valley Cancer Institute and Research Center
Eugene, Oregon, 97401
- Not yet recruiting
Florida Cancer Specialists & Research Institute
Fort Myers, Florida, 33901
- Not yet recruiting
Banner Md Anderson Cancer Center
Gilbert, Arizona, 85234
- Recruiting
Marin Cancer Care
Greenbrae, California, 94904
- Not yet recruiting
John Theurer Cancer Center, Hackensack University Medical Center
Hackensack, New Jersey, 07601
- Not yet recruiting
The University of Texas-Md Anderson Cancer Center
Houston, Texas, 77030
- Not yet recruiting
Rocky Mountain Cancer Centers-Lone Tree
Lone Tree, Colorado, 80124
- Not yet recruiting
University of California, Los Angeles Medical Center
Los Angeles, California, 90095
- Not yet recruiting
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
- Not yet recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
- Not yet recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
- Not yet recruiting
Icahn School of Medicine At Mount Sinai
New York, New York, 10029
- Not yet recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
- Not yet recruiting
Weill Cornell Medical College - Newyork-Presbyterian Hospita
New York, New York, 10065
- Not yet recruiting
Virginia Oncology Associates (Brock Cancer Center)
Norfolk, Virginia, 23502
- Not yet recruiting
Stanford Cancer Center
Palo Alto, California, 94304
- Not yet recruiting
Thomas Jefferson University Sidney Kimmel Medical College
Philadelphia, Pennsylvania, 19107
- Not yet recruiting
Oregon Health and Science University
Portland, Oregon, 97239
- Not yet recruiting
Strong Memorial Hospital University of Rochester Medical Center
Rochester, New York, 14642
- Not yet recruiting
Huntsman Cancer Institute At University of Utah
Salt Lake City, Utah, 84112
- Not yet recruiting
Ut Health Science Center At San Antonio
San Antonio, Texas, 78229
- Not yet recruiting
University of Washington - Fred Hutch Cancer Center
Seattle, Washington, 98109
- Not yet recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
- Not yet recruiting
Texas Oncology-Tyler
Tyler, Texas, 75702
- Not yet recruiting
Medstar Georgetown Medical Center, Inc
Washington D.C., District of Columbia, 20007
- Not yet recruiting
Cleveland Clinic
Weston, Florida, 33331
- Not yet recruiting
The University of Kansas Cancer Center
Westwood, Kansas, 66205
- Not yet recruiting
University of Massachusetts Medical School
Worcester, Massachusetts, 01655
Italy16 sites, 16 recruiting
- Not yet recruiting
Aou Policlinico Consorziale Bari - Uo Ematologia Con Trapianto
Bari, 70124
- Not yet recruiting
Asst Papa Giovanni Xxiii (Azienda Ospedaliera Papa Giovanni Xxiii)
Bergamo, 24127
- Not yet recruiting
Istituto Di Ematologia L. E A. Seragnoli-Azienda Ospedaliero Universitaria Policlinico S. Orsola Mal
Bologna, 40138
- Not yet recruiting
Azienda Ospedaliero Universitaria Policlinico Gaspare Rodolico - San Marco
Catania, 95123
- Not yet recruiting
Universita Degli Studi Di Firenze - Azienda Ospedaliero-Universitaria Careggi (Aouc)
Florence, 50134
- Not yet recruiting
Irccs - Azienda Ospedaliera Universitaria - Ist San Martino
Genova, 16132
- Not yet recruiting
Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori, Ematologia
Meldola, 47014
- Not yet recruiting
Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico Di Milano
Milan, 20122
- Not yet recruiting
Ao Maggiore Della Carita
Novara, 28100
- Not yet recruiting
Universita Degli Studi Di Pavia-Fondazione Irccs Policlinico San Matteo
Pavia, 27100
- Not yet recruiting
Ospedale S. Eugenio
Rome, 00144
- Not yet recruiting
Universita Degli Studi Di Roma La Sapienza - Umberto I Policlinico Di Roma
Rome, 00161
- Not yet recruiting
Universita Cattolica Del Sacro Cuore - Policlinico Universitario Agostino Gemelli
Rome, 00168
- Not yet recruiting
Ao Ordine Mauriziano Di Torino
Torino, 10128
- Not yet recruiting
Azienda Ospedaliero-Universitaria Santa Maria Della Misericordia
Udine, 33100
- Not yet recruiting
Universita Degli Studi Di Verona
Verona, 37100
Japan15 sites, 15 recruiting
- Not yet recruiting
Juntendo University Hospital
Bunkyō City, 113-8431
- Not yet recruiting
Nippon Medical School Hospital
Bunkyō City, 113-8603
- Not yet recruiting
University of Yamanashi Hospital
Chūō, 409-3898
- Not yet recruiting
Kyushu University Hospital
Fukuoka, 812-8582
- Not yet recruiting
Fukushima Medical University Hospital
Fukushima, 960-1295
- Not yet recruiting
Kansai Medical University Hospital
Hirakata, 5731191
- Not yet recruiting
Kagoshima University Hospital
Kagoshima, 890-8520
- Not yet recruiting
National Cancer Center Hospital East
Kashiwa-shi, 277-8577
- Not yet recruiting
Kobe City Medical Center General Hospital
Kobe, 650-0047
- Not yet recruiting
University of Miyazaki Hospital
Miyazaki, 889-1692
- Not yet recruiting
Osaka Metropolitan University Hospital
Osaka, 545-8586
- Not yet recruiting
Kindai University Hospital
Sakai, 590-0197
- Not yet recruiting
Tokyo Medical University Hospital
Shinjuku-ku, 160-0023
- Not yet recruiting
Ehime University Hospital
Tōon, 791-0295
- Not yet recruiting
Mie University Graduate School of Medicine
Tsu, 514-8507
Spain15 sites, 15 recruiting
- Not yet recruiting
Hospital General Unviersitario de Alicante
Alicante, 03010
- Not yet recruiting
Hospital Universitario Vall D'Hebron
Barcelona, 08035
- Not yet recruiting
Hospital Clinic de Barcelona (Hospital Clinic I Provincial)
Barcelona, 08036
- Not yet recruiting
Hospital Universitario de Basurto
Bilbao, 48013
- Not yet recruiting
Instituto Catalan de Oncologia - Hospital Duran I Reynals
L'Hospitalet de Llobregat, 08908
- Not yet recruiting
Hospital Universitario de Gran Canaria Doctor Negrin
Las Palmas de Gran Canaria, 35010
- Not yet recruiting
Hospital Universitario Ramon Y Cajal
Madrid, 28034
- Not yet recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
- Not yet recruiting
Hospital Universitario Puerta de Hierro de Majadahonda
Majadahonda, 28222
- Not yet recruiting
Hospital Universitario Virgen de La Victoria
Málaga, 29010
- Not yet recruiting
Hospital Universitari Son Espases
Palma, 07120
- Not yet recruiting
Hospital Clinico Universitario de Salamanca
Salamanca, 37007
- Not yet recruiting
Hospital Clinico Universitario de Santiago de Compostela
Santiago de Compostela, 15706
- Not yet recruiting
Hospital Universitario Doctor Peset
Valencia, 46017
- Not yet recruiting
Hospital Universitario Miguel Servet ( Hospital Infantil)
Zaragoza, 05009
Germany12 sites, 12 recruiting
- Not yet recruiting
Uniklinik Rwth Aachen Medizinische Klinik Iv
Aachen, 52074
- Not yet recruiting
Charite - Universitaetsmedizin Berlin
Berlin, 10117
- Not yet recruiting
Bag Onkologische Gemeinschaftspraxis Illmer, Jacobasch, Wolf, Freiberg-Richter Fae Fur Innere Medizi
Dresden, 01307
- Not yet recruiting
Universitaetsklinikum Freiburg
Freiburg im Breisgau, 79106
- Not yet recruiting
Universitaetsklinikum Halle
Halle, 06120
- Not yet recruiting
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, 20246
- Not yet recruiting
Medizinische Hochschule Hannover, Hannover Medical School
Hanover, 30625
- Not yet recruiting
Universitaetsklinikum Des Saarlandes Und Medizinische Fakultaet Der Universitaet Des Saarlandes
Homburg, 66421
- Not yet recruiting
Universitaetsklinikum Jena
Jena, 07747
- Not yet recruiting
Universitaetsklinikum Schleswig-Holstein (Uksh) - Campus Luebeck
Lübeck, 23562
- Not yet recruiting
Medizinische Fakultaet Mannheim Der Universitaet Heidelberg
Mannheim, 68167
- Not yet recruiting
Johannes Wesling Klinikum Minden
Minden, 32429
Australia10 sites, 10 recruiting
- Not yet recruiting
Sunshine Coast University Hospital
Birtinya, Queensland, 04575
- Not yet recruiting
Blacktown Cancer & Haematology Centre-Blacktown Hospital
Blacktown, New South Wales, 02148
- Not yet recruiting
Royal Brisbane and Women'S Hospital
Brisbane, Queensland, 04029
- Not yet recruiting
Rockingham General Hospital
Cooloongup, 06168
- Not yet recruiting
The Canberra Hospital
Garran, 02605
- Not yet recruiting
Gosford Hospital (Gh) - Central Coast Cancer Centre
Gosford, New South Wales, 02250
- Not yet recruiting
Liverpool Hospital - South Western Sydney Local Health District
Liverpool, New South Wales, 02170
- Not yet recruiting
Peter Maccallum Cancer Centre
Melbourne, Victoria, 03000
- Not yet recruiting
Box Hill Hospital
Melbourne, Victoria, 03128
- Not yet recruiting
Royal Perth Hospital
Perth, 06000
France9 sites, 9 recruiting
- Not yet recruiting
Chu D'Amiens-Picardie - Hopital Sud
Amiens, 80054
- Not yet recruiting
Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest
Bordeaux, 33076
- Not yet recruiting
Chu de Brest Hopital de La Cavale Blanche Cic Hematologie
Brest, 29200
- Not yet recruiting
Hospital Henri Mondor
Créteil, 94000
- Not yet recruiting
Hopital Bicetre - Paris Sud (Ap-Hp)
Le Kremlin-Bicêtre, 94275
- Not yet recruiting
Centre Hospitalier Universitaire de Nice,Hopital L Archet
Nice, 06200
- Not yet recruiting
Hospital Saint-Louis - Aphp
Paris, 75010
- Not yet recruiting
Centre Hospitalier Universitaire de Poitiers La Miletrie
Poitiers, 86021
- Not yet recruiting
Institut Claudius Regaud Cancer Comprehensive Center - Iuct Oncopole
Toulouse, 31059
United Kingdom8 sites, 8 recruiting
- Not yet recruiting
Addenbrooke'S Hospital - Cambridge University Hospitals Nhs Foundation Trust
Cambridge, CB2 0QQ
- Not yet recruiting
Western General Hospital - Lothian Health Board
Edinburgh, EH4 2XU
- Not yet recruiting
Northwick Park Hospital - London North West University Healthcare Nhs Trust
Harrow, HA1 3UJ
- Not yet recruiting
St James'S University Hospital - Leeds Teaching Hospitals Nhs Trust
Leeds, LS9 7TF
- Not yet recruiting
Guy'S Hospital - Guy'S & St Thomas' Nhs Foundation Trust
London, SE1 9RT
- Not yet recruiting
Northern Centre For Cancer Care - the Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Newcastle upon Tyne, NE7 7DN
- Not yet recruiting
Cancer and Haematology Centre-the Churchill Hospital-Oxford University Hospitals
Oxford, OX3 7LJ
- Not yet recruiting
Royal Cornwall Hospital - Royal Cornwall Hospitals Nhs Trust
Penzance, TR18 2PF
Canada7 sites, 7 recruiting
- Not yet recruiting
Margaret and Charles Juravinski Cancer Center
Hamilton, Ontario, L8V 5C2
- Not yet recruiting
Queens University, Kingston General Hospital (Kgh), Kingston Health Sciences Centre (Khsc)
Kingston, Ontario, K7L 2V7
- Not yet recruiting
Sir Mortimer B. Davis - Jewish General Hospital
Montreal, Quebec, H3T 1E2
- Not yet recruiting
McGill University Health Centre - Glen Site, Centre For Innovative Medicine
Montreal, Quebec, H4A 3J1
- Not yet recruiting
Hotel-Dieu de Levis
Québec, Quebec, G6V 3Z1
- Not yet recruiting
University Health Network (Uhn) - Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
- Not yet recruiting
St. Paul'S Hospital (Sph), Providence Health Care, University of British Columbia
Vancouver, British Columbia, V6Z 1Y6
Poland7 sites, 7 recruiting
- Not yet recruiting
Uniwersyteckie Centrum Kliniczne (Uck)
Gdansk, 80-952
- Not yet recruiting
Pratia Onkologia Katowice
Katowice, 40-519
- Not yet recruiting
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie
Krakow, 31-501
- Not yet recruiting
Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im. M. Kopernika W Lodzi
Lodz, 93-513
- Not yet recruiting
Uniwersytecki Szpital Kliniczny Nr 1 W Lublinie
Lublin, 20-081
- Not yet recruiting
Specjalistyczny Szpital Im. Dr Alfreda Sokolowskiego
Wałbrzych, 58-309
- Not yet recruiting
Instytut Hematologii I Transfuzjologii (Iht) (Institute of Haematology and Transfusion Medicine)
Warsaw, 02-776
South Korea7 sites, 7 recruiting
- Not yet recruiting
Pusan National University Hospital (Pnuh)
Busan, 49241
- Not yet recruiting
Seoul National University Bundang Hospital (Snubh)
Seongnam-si, 13620
- Not yet recruiting
Korea University Anam Hospital
Seoul, 02841
- Not yet recruiting
Seoul National University Hospital
Seoul, 03080
- Not yet recruiting
Severance Hospital Yonsei University Health System
Seoul, 03722
- Not yet recruiting
Asan Medical Center
Seoul, 05505
- Not yet recruiting
The Catholic University of Korea Seoul St. Mary'S Hospital
Seoul, 06591
Belgium6 sites, 6 recruiting
- Not yet recruiting
Jules Bordet Lnstitute
Anderlecht, 01070
- Not yet recruiting
Centre Hospitalier Universitaire (Chu) Brugmann (Brugmann University Hospital (Uh)) - Victor Horta
Brussels, 1020
- Not yet recruiting
Universitair Ziekenhuis Leuven
Leuven, 03000
- Not yet recruiting
Centre Hospitalier Universitaire de Liege - Sart Tilman
Liège, 04000
- Not yet recruiting
Algemeen Ziekenhuis Deltaaretaie
Roeselare, 08800
- Not yet recruiting
Universite Catholique de Louvain (Ucl) - Cliniques Universitaires Saint-Luc
Woluwe-Saint-Lambert, 01200
Austria5 sites, 5 recruiting
- Not yet recruiting
Lkh - Medizinische Universitaet Graz
Graz, 08036
- Not yet recruiting
Landeskrankenhaus (Lkh) Leoben - Standort Leoben
Leoben, 08700
- Not yet recruiting
Ordensklinikum Linz Gmbh Elisabethinen
Linz, 04020
- Not yet recruiting
Medizinische Universitaet Wien, Akh Wien
Vienna, 01090
- Not yet recruiting
Klinikum Wels-Grieskirchen Gmbh
Wels, 04600
Czechia5 sites, 5 recruiting
- Not yet recruiting
Fakultni Nemocnice Brno
Brno, 625 00
- Not yet recruiting
Fakultni Nemocnice Ostrava
Ostrava-poruba, 708 52
- Not yet recruiting
Faculty Hospital Kralovske Vinohrady
Prague, 100 34
- Not yet recruiting
Vseobecna Fakultni Nemocnice V Praze
Prague, 12808
- Not yet recruiting
Ustav Hematologie A Krevni Transfuze (Uhkt)
Prague, 12820
Netherlands5 sites, 5 recruiting
- Not yet recruiting
Amsterdam Universitair Medisch Centrum, Locatie Amsterdam Medisch Centrum
Amsterdam, 1105 AZ
- Not yet recruiting
University Medical Center Groningen
Groningen, 9713 GZ
- Not yet recruiting
Radboud University Medical Center
Nijmegen, 6525 GA
- Not yet recruiting
Erasmus University Medical Center
Rotterdam, 3015 GD
- Not yet recruiting
Universitair Medisch Centrum Utrecht (Umc Utrecht)
Utrecht, 3584 CX
Switzerland4 sites, 4 recruiting
- Not yet recruiting
University Hospital Bern (Inselspital)
Bern, 03010
- Not yet recruiting
Hoch Health Ostschweiz, Kantonsspital St. Gallen
Sankt Gallen, 09007
- Not yet recruiting
Center of Oncology, Hematology and Transfusionmedicine
Tellstrasse, 05001
- Not yet recruiting
Universitatsspital Zurich
Zurich, 08091
Hungary3 sites, 3 recruiting
- Not yet recruiting
Semmelweis University-Internal Medicine and Haematology
Budapest, 01088
- Not yet recruiting
Debreceni Egyetem Klinikai Kozpont
Debrecen, 04032
- Not yet recruiting
University of Pecs
Pécs, 07624
Norway1 site, 1 recruiting
- Not yet recruiting
Haukeland University Hospital
Bergen, 05021
Singapore1 site, 1 recruiting
- Not yet recruiting
Singapore General Hospital
Singapore, 169608
About this study
Official title: A Phase 3, Randomized, Open-Label Study of INCA033989 Versus Best Available Therapy in Participants With Essential Thrombocythemia and a CALR Mutation Previously Treated With Cytoreductive Therapy (EXCALIBUR-ET2)
This study is being conducted to evaluate INCA033989 versus best available therapy in participants with essential thrombocythemia and a CALR mutation previously treated with cytoreductive therapy.
- Conditions
- Essential Thrombocythemia
- Being tested
- INCA033989, Best Available Treatment
- Keywords
- calreticulin (CALR), mutCALR
- Medical subject headings
- Thrombocythemia, Essential
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INCA033989Drug
Administered intravenous (IV) in accordance with the protocol-defined requirements.
Best Available TreatmentDrug
Also called BAT could include:, • HU, • ANA, • PEG interferon alfa-2a
Best Available Therapy (BAT) will be selected by the investigator.
| Study group | Role | What they receive |
|---|---|---|
| INCA033989 | Experimental | Administered intravenous (IV) in accordance with the protocol-defined requirements. Receives: Drug: INCA033989 |
| Best Available Therapy (BAT) | Experimental | Best Available Therapy (BAT) will be selected by the investigator. Receives: Drug: Best Available Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Durable clinicohematologic response (DCR)
Normalization of platelet and white blood cell (WBC) counts and absence of disease progression as defined in the protocol.
Measured: Week 24
Secondary outcomes (12)
Reduction from baseline in calreticulin exon 9 frameshift mutation(s) (mutCLAR) variant allele frequency (VAF)
Reduction in mutCALR VAF as defined in the protocol.
Measured: Week 24
Durable clinicohematologic response (DCR)
Normalization of platelet and white blood cell (WBC) counts and absence of disease progression as defined in the protocol.
Measured: Week 48
Durable partial clinicohematologic response (DPR)
Improvement of platelet and white blood cell (WBC) counts and absence of disease progression as defined in the protocol.
Measured: Week 24
Durable partial clinicohematologic response (DPR)
Improvement of platelet and white blood cell (WBC) counts and absence of disease progression as defined in the protocol.
Measured: Week 48
Longest duration of complete hematologic response (CHR)
Longest time from documented CHR until the loss of CHR as defined in the protocol.
Measured: Up to Week 48
Number of Participants with Treatment Emergent Adverse Events (TEAE)
Defined as any adverse event occurring after the first dose of study drug until up to 60 days after the last dose of study drug.
Measured: Up to Week 48 and 60 days after last dose
TEAEs leading to dose interruptions, dose reductions or discontinuation of study treatment
TEAEs leading to dose interruptions, dose reductions or discontinuation of study treatment.
Measured: Up to Week 48 and 60 days after last dose
Number of participants with a reduction in mutCALR VAF
Number of participants with a reduction in mutCALR VAF as defined in the protocol.
Measured: Week 24 and Week 48
Molecular response
Overall reduction in mutCALR VAF as defined in the protocol.
Measured: Week 24 and Week 48
Change from baseline in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) total symptom score (TSS)
Defined as the proportion of participants who achieve a protocol defined reduction in TSS.
Measured: Up to Week 48
Change from baseline in Brief Fatigue Inventory (BFI) fatigue score
The BFI is a 9 item scored from 0 (no fatigue) -10 (as bad as you can imagine), items are averaged with total score from 0-10, with higher score indicating more fatigue.
Measured: Up to Week 48
Patient Global Impression of Change (PGIC) score
The PGIC is based on a 7-point scale and the participant will rate each question from the start of treatment as 1-very much improved, 2-much improved, 3-minimally improved, 4-no change, 5-minimally worse, 6-much worse, and 7-very much worse.
Measured: Up to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2026
- Study start8 Sep 2026
- Primary completion15 Jun 2029 (estimated)
- Study completion1 Nov 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Essential ThrombocythemiaStudies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 426 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Incyte Medical Monitor, Study director, Incyte Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07623200
- Sponsor's protocol ID
- INCA033989-304
- Other IDs
- 2026-525398-38-00
- Acronym
- EXCALIBUR-ET2
- Status last verified
- Oct 2026
- First submitted
- 29 May 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Open-Label Study of INCA033989 Versus Best Available Therapy in Participants With Essential Thrombocythemia and a CALR Mutation Previously Treated With Cytoreductive Therapy (EXCALIBUR-ET2)
- ClinicalTrials.gov ID
- NCT07623200
- Acronym / sponsor ID
- EXCALIBUR-ET2 / INCA033989-304
- Conditions
- Essential Thrombocythemia
- Keywords
- calreticulin (CALR), mutCALR
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 426 participants (estimated)
- Lead sponsor
- Incyte CorporationIndustry (pharma, biotech, devices)
- Study start
- 8 Sep 2026 (actual)
- Primary completion
- 15 Jun 2029 (estimated)
- Study completion
- 1 Nov 2030 (estimated)
- First posted
- 3 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being conducted to evaluate INCA033989 versus best available therapy in participants with essential thrombocythemia and a CALR mutation previously treated with cytoreductive therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| INCA033989 | Experimental | Drug: INCA033989Administered intravenous (IV) in accordance with the protocol-defined requirements. |
| Best Available Therapy (BAT) | Experimental | Drug: Best Available TreatmentBest Available Therapy (BAT) will be selected by the investigator. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Confirmed diagnosis of high-risk ET.
- Presence of mutCALR.
- Prior treatment with at least 1 cytoreductive therapy.
Key exclusion criteria (6 listed)
- Presence of any hematologic malignancy other than ET.
- Major bleeding or thrombosis within the last 3 months prior to study enrollment.
- Any prior allogenic or autologous stem-cell transplantation.
- Unresolved toxicity ≥ Grade 2 from previous therapy except for stable chronic toxicities (Grade 2) not expected to resolve, such as stable Grade 2 peripheral neuropathy.
- Prior nonhematologic malignancy except for the following: Malignancy treated with curative intent and with no evidence of active disease for more than 2 years before screening. Adequately treated carcinoma in situ without current evidence of disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INCA033989Administered intravenous (IV) in accordance with the protocol-defined requirements. | Drug | INCA033989 |
| Best Available TreatmentAlso: BAT could include:, • HU, • ANA, • PEG interferon alfa-2aBest Available Therapy (BAT) will be selected by the investigator. | Drug | Best Available Therapy (BAT) |
Primary outcome
Durable clinicohematologic response (DCR)
Time frame: Week 24
Normalization of platelet and white blood cell (WBC) counts and absence of disease progression as defined in the protocol.
12 secondary outcomes
Reduction from baseline in calreticulin exon 9 frameshift mutation(s) (mutCLAR) variant allele frequency (VAF)
Time frame: Week 24
Durable clinicohematologic response (DCR)
Time frame: Week 48
Durable partial clinicohematologic response (DPR)
Time frame: Week 24
Durable partial clinicohematologic response (DPR)
Time frame: Week 48
Longest duration of complete hematologic response (CHR)
Time frame: Up to Week 48
Number of Participants with Treatment Emergent Adverse Events (TEAE)
Time frame: Up to Week 48 and 60 days after last dose
TEAEs leading to dose interruptions, dose reductions or discontinuation of study treatment
Time frame: Up to Week 48 and 60 days after last dose
Number of participants with a reduction in mutCALR VAF
Time frame: Week 24 and Week 48
Molecular response
Time frame: Week 24 and Week 48
Change from baseline in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) total symptom score (TSS)
Time frame: Up to Week 48
Change from baseline in Brief Fatigue Inventory (BFI) fatigue score
Time frame: Up to Week 48
Patient Global Impression of Change (PGIC) score
Time frame: Up to Week 48
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- A Phase 3 Study of INCA033989 Versus Best Available Therapy in Participants With Essential Thrombocythemia (EXCALIBUR-ET2)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Incyte Medical Monitor study director
Incyte Corporation
178 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing INCA033989 and Best Available Treatment in people with Essential Thrombocythemia, run by Incyte Corporation at 178 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 178 sites in United States, Italy, Japan, Spain, Germany and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Incyte Corporation Call Center (US) (1.855.463.3463, medinfo@incyte.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Durable clinicohematologic response (DCR) (time frame: Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.