Hematologic MalignanciesPhase 2NCT04728893
Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)
A Phase 2 study testing Nemtabrutinib in people with Hematologic Malignancies and Waldenstroms Macroglobulinaemia, run by Merck Sharp & Dohme LLC at 121 sites in 22 countries.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of nemtabrutinib (formerly ARQ 531) in participants with hematologic malignancies of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Richter's transformation, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancies, Waldenstroms Macroglobulinaemia, Non-Hodgkins Lymphoma
- What is being tested?
- Nemtabrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 490 participants
- Where
- 121 sitesin 22 countries
- Study dates
- 5 Apr 2021to 4 Jan 2029
- Phase
- Phase 2
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
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before C1D1 (the first dose of study treatment)
- Has a life expectancy of at least 3 months, based on the investigator assessment
- Has the ability to swallow and retain oral medication
- Participants who are Hepatitis B surface antigen (HBsAg)-positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
- Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
- Has adequate organ function
Show all 30Show fewer
- Male participants agree to refrain from donating sperm and agree to either remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for at least the time required to eliminate the study intervention after last dose of study intervention
- Female participants assigned female sex at birth who are not pregnant or breastfeeding are eligible to participate if not a participant of childbearing potential (POCBP), or if a POCBP they either use a contraceptive method that is highly effective OR remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle during the intervention period and for at least to eliminate study intervention after the last dose of study intervention
- Participants with Human immunodeficiency virus (HIV) are eligible if they meet all of the following: the CD4 count is >350 cells/uL at screening, the HIV viral load is below the detectable level, are on a stable ART regimen for at least 4 weeks prior to study entry, and are compliant with their ART
- Part 1 and Part 2 (Cohorts A to C and J)
- Has a confirmed diagnosis of Chronic lymphocytic leukemia/ Small lymphocytic lymphoma (CLL/SLL) with
- At least 2 lines of prior therapy (Part 1 only)
- Part 2 Cohort A: CLL/SLL participants who are relapsed or refractory to prior therapy with a covalent, irreversible Bruton's tyrosine kinase inhibitor (BTKi), and a B-cell lymphoma 2 inhibitor (BCL2i). CLL participants must have received and failed, been intolerant to, or determined by their treating physician to be a poor phosphoinositide 3-kinase inhibitor (PI3Ki) candidate or ineligible for a PI3Ki per local guidelines
- Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory following at least 1 line of prior therapy and are BTKi treatment naive
- Part 2 Cohort C: CLL/SLL participants with 17p deletion or tumor protein p53 (TP53) mutation who are relapsed or refractory following at least 1 line of prior therapy
- Part 2 Cohort J: CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi and BCL2i. NOTE: As of Protocol Amendment 09, at least 10 CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi, BCL2i and noncovalent/reversible BTKi (all three classes of therapies are required) will be enrolled into Cohort J
- Has active disease for CLL/SLL clearly documented to initiate therapy
- For SLL participants in Part 2: Has evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate at Screening (optional for participants enrolling in Part 1)
- Part 2 (Cohorts D to G)
- Has a confirmed diagnosis of and meets the following prior therapy requirements:
- Participants with Richter's transformation who are relapsed or refractory following at least 1 line of prior therapy (Cohort D)
- Participants with pathologically confirmed Mantle-cell lymphoma (MCL), documented by either overexpression of cyclin D1 or t (11;14), who are relapsed or are refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort E)
- Participants with Marginal zone lymphoma (MZL) (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to at least one prior line of systemic therapy including an anti-CD20-based regimen
- Participants with Follicular lymphoma (FL) who are relapsed or refractory to chemoimmunotherapy and immunomodulatory agents (such as lenalidomide based regimen) (Cohort G)
- Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral Computed tomography (CT) scan
- Has a lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate (Cohort D) at Screening
- Part 2 (Cohort H): confirmed diagnosis of Waldenström's macroglobulinemia (WM); participants who are relapsed or refractory to standard therapies for WM including chemoimmunotherapy and a covalent irreversible BTKi
- Has active disease defined as 1 of the following: systemic symptoms, physical findings, laboratory abnormalities, coexisting disease
- Has measurable disease, satisfying any of the following: at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan (minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis); IgM ≥450 mg/dL; or bone marrow infiltration of 10%
- Has fresh bone marrow aspirate or a lymph node biopsy for biomarker analysis at Screening or a lymph node biopsy from an archival
Who cannot join
- Has active HBV/HCV infection (Part 1 and Part 2)
- Has a history of malignancy ≤3 years before providing documented informed consent. Participants with basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy are not excluded. Participants with low-risk, early-stage prostate cancer (T1-T2a, Gleason score ≤6, and prostate-specific antigen <10 ng/mL) either treated with definitive intent or untreated in active surveillance with SD are not excluded
- Has active central nervous system (CNS) disease
- Has an active infection requiring systemic therapy
- Has received prior systemic anti-cancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) before C1D1
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
- Has any clinically significant gastrointestinal abnormalities that might alter absorption
- History of severe bleeding disorders
Trial locations and contacts
121 sites in 22 countries. Contact the study team or a site near you to ask about taking part.
121 sites in 22 countries
China19 sites, 15 recruiting
- Recruiting
Peking University Third Hospital-Hematology ( Site 2827)
Beijing, Beijing Municipality, 100191
Study Coordinator, 010-82266699
- Recruiting
The First Hospital of Jilin University-Hematology ( Site 2803)
Changchun, Jilin, 130021
Study Coordinator, 0431-88786014
- Recruiting
The Second Xiangya Hospital of Central South University ( Site 2820)
Changsha, Hunan, 410011
Study Coordinator, +8613975806137
- Recruiting
Hunan Cancer Hospital ( Site 2822)
Changsha, Hunan, 410013
Study Coordinator, 0731-88651669
- Recruiting
West China Hospital Sichuan University ( Site 2810)
Chengdu, Sichuan, 610041
Study Coordinator, +86028-85422114
- Active, not recruiting
The Second Affiliated Hospital of Chongqing Medical University ( Site 2825)
Chongqing, Chongqing Municipality, 400072
- Active, not recruiting
Sun Yat-sen University Cancer Center-Internal Medicine ( Site 2824)
Guangzhou, Guangdong, 510060
- Recruiting
The First Affiliated Hospital, Zhejiang University ( Site 2826)
Hangzhou, Zhejiang, 310002
Study Coordinator, 057187236114
- Active, not recruiting
Anhui Provincial Hospital ( Site 2808)
Hefei, Anhui, 230071
- Recruiting
Liuzhou People's Hospital ( Site 2817)
Liuzhou, Guangxi, 545006
Study Coordinator, +8607722662950
- Recruiting
The First Affiliated Hospital of Nanchang University ( Site 2815)
Nanchang, Jiangxi, 330006
Study Coordinator, 13970038386
- Recruiting
Jiangsu Province Hospital ( Site 2823)
Nanjing, Jiangsu, 210029
Study Coordinator, 025-86211033
- Recruiting
Guangxi Medical University Cancer Hospital ( Site 2814)
Nanning, Guangxi, 530028
Study Coordinator, +8607715323174
- Recruiting
Fudan University Shanghai Cancer Center ( Site 2801)
Shanghai, Shanghai Municipality, 200032
Study Coordinator, +8602164175590
- Recruiting
Huashan Hospital, Fudan University ( Site 2821)
Shanghai, Shanghai Municipality, 200040
Study Coordinator, 021-52889999
- Recruiting
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Unio ( Site 2800)
Tianjin, Tianjin Municipality, 301617
Study Coordinator, +8615900265415
- Recruiting
Wuhan Union Hospital ( Site 2816)
Wuhan, Hubei, 430022
Study Coordinator, +8618627091655
- Completed
The Affiliated Hospital of Xuzhou Medical College ( Site 2818)
Xuzhou, Jiangsu, 221000
- Recruiting
Henan Cancer Hospital-hematology department ( Site 2802)
Zhengzhou, Henan, 450008
Study Coordinator, 0371-65588007
United States11 sites, 7 recruiting
- Recruiting
UT Southwestern-Harold C. Simmons Cancer Center ( Site 2730)
Dallas, Texas, 75390
Study Coordinator, 972-695-9450
- Recruiting
Colorado Blood Cancer Institute ( Site 2726)
Denver, Colorado, 80218
Study Coordinator, 720-754-4800
- Recruiting
Astera Cancer Care ( Site 2732)
East Brunswick, New Jersey, 08816
Study Coordinator, 732-672-6405
- Completed
Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 2708)
Fargo, North Dakota, 58102
- Recruiting
John Theurer Cancer Center at Hackensack University Medical Center ( Site 2704)
Hackensack, New Jersey, 07601
Study Coordinator, 551-996-3003
- Recruiting
University of California San Diego Moores Cancer Center ( Site 2717)
La Jolla, California, 92093-0698
Study Coordinator, 858-534-5201
- Completed
The University of Louisville, James Graham Brown Cancer Center ( Site 2729)
Louisville, Kentucky, 40202
- Active, not recruiting
Mayo Clinic - Rochester ( Site 2706)
Rochester, Minnesota, 55905
- Recruiting
Medical Oncology Associates (Summit Cancer Centers) ( Site 2710)
Spokane, Washington, 99208
Study Coordinator, 509-462-2273
- Recruiting
Highlands Oncology Group ( Site 2728)
Springdale, Arkansas, 72762
Study Coordinator, 479-872-8130
- Completed
Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site 2724)
Torrance, California, 90502
Italy8 sites, 6 recruiting
- Active, not recruiting
Istituto Tumori Giovanni Paolo II ( Site 1409)
Bari, 70124
- Recruiting
A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 1400)
Bologna, 40138
Study Coordinator, +390516363680
- Recruiting
ASST Spedali Civili di Brescia ( Site 1408)
Brescia, 25123
Study Coordinator, +39 0303996416
- Recruiting
IRCCS Ospedale San Raffaele ( Site 1402)
Milan, 20132
Study Coordinator, 00390226434797
- Recruiting
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1403)
Naples, 80131
Study Coordinator, +39 0815903 382
- Recruiting
Fondazione IRCCS Policlinico San Matteo ( Site 1407)
Pavia, 27100
Study Coordinator, +39 0382503084
- Recruiting
IRCCS - Arcispedale Santa Maria Nuova ( Site 1405)
Reggio Emilia, 42123
Study Coordinator, +39 0522295654
- Completed
Policlinico Umberto I ( Site 1404)
Roma, 00161
United Kingdom8 sites, 8 recruiting
- Recruiting
Bristol Haematology and Oncology Centre ( Site 2610)
Bristol, Bristol, City of, BS2 8ED
Study Coordinator, 01173426733
- Recruiting
Sarah Cannon Research Institute UK ( Site 2612)
London, London, City of, W1G 6AD
Study Coordinator, 02032195234
- Recruiting
The Christie NHS Foundation Trust ( Site 2602)
Manchester, M20 4BX
Study Coordinator, 01619561217
- Recruiting
GenesisCare - Cambridge ( Site 2611)
Newmarket, Suffolk, CB8 7XN
Study Coordinator, 01223 655145
- Recruiting
Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 2601)
Nottingham, England, NG5 1PF
Study Coordinator, +441159691169
- Recruiting
GenesisCare - Oxford ( Site 2607)
Oxford, Oxfordshire, OX4 6LB
Study Coordinator, +447989474250
- Recruiting
The Royal Marsden NHS Foundation Trust. ( Site 2606)
Sutton, Surrey, SM2 5PT
Study Coordinator, 020 8642 6011
- Recruiting
GenesisCare - Windsor ( Site 2608)
Windsor, England, SL4 3HD
Study Coordinator, +447989474250
Israel7 sites, 7 recruiting
- Recruiting
Ha Emek Medical Center ( Site 1305)
Afula, 1834111
Study Coordinator, 972-46494052
- Recruiting
Soroka Medical Center ( Site 1307)
Beersheba, 8410101
Study Coordinator, +97286403827
- Recruiting
Rambam Medical Center ( Site 1301)
Haifa, 3109601
Study Coordinator, +97247772547
- Recruiting
Hadassah Ein Karem Jerusalem ( Site 1300)
Jerusalem, 9112001
Study Coordinator, +97226778180
- Recruiting
Chaim Sheba Medical Center ( Site 1302)
Ramat Gan, 5262001
Study Coordinator, +97235308401
- Recruiting
Kaplan Medical Center ( Site 1304)
Rehovot, 76100
Study Coordinator, +97289441726
- Recruiting
Sourasky Medical Center ( Site 1303)
Tel Aviv, 6423906
Study Coordinator, +97236973782
Spain7 sites, 7 recruiting
- Recruiting
CHUAC-Complejo Hospitalario Universitario A Coruña ( Site 2005)
A Coruña, La Coruna, 15006
Study Coordinator, 34981178000
- Recruiting
Hospital General Universitario de Alicante ( Site 2007)
Alicante, 03010
Study Coordinator, 965 93 30 00
- Recruiting
Hospital Universitari Vall d'Hebron ( Site 2001)
Barcelona, 08035
Study Coordinator, +34934893806
- Recruiting
Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 2000)
L'Hospitalet de Llobregat, Barcelona, 08908
Study Coordinator, +34932607750
- Recruiting
Hospital Universitario 12 de Octubre ( Site 2003)
Madrid, 28041
Study Coordinator, +34917792809
- Recruiting
Hospital Puerta de Hierro ( Site 2009)
Madrid, 28222
Study Coordinator, +34911916000
- Recruiting
Hospital Universitario de Salamanca ( Site 2002)
Salamanca, Castille and León, 37007
Study Coordinator, 34923 29 11 00x55974
Argentina6 sites, 5 recruiting
- Recruiting
Centro de Educación Médica e Investigaciones Clínicas (CEMIC) ( Site 0103)
Buenos Aires, Buenos Aires F.D., C1431FWO
Study Coordinator, +541152990247
- Recruiting
FUNDALEU ( Site 0104)
Caba, C1114AAN
Study Coordinator, 5411 48771046
- Recruiting
Hospital Aleman ( Site 0102)
Ciudad Autonoma de Buenos Aires, Buenos Aires, C1118AAT
Study Coordinator, +541148277000
- Recruiting
Hospital Privado Universitario de Córdoba ( Site 0107)
Córdoba, X5016KEH
Study Coordinator, +541569634187
- Completed
Fundacion Centro Oncologico de Integración Regional-Medical Oncology ( Site 0110)
Mendoza, M5500AYB
- Recruiting
Fundacion Estudios Clinicos ( Site 0112)
Rosario, Santa Fe Province, S2000DEJ
Study Coordinator, +54 0341 238 4171
Canada5 sites, 5 recruiting
- Recruiting
Arthur J.E. Child Comprehensive Cancer Centre ( Site 0401)
Calgary, Alberta, T2N 5G2
Study Coordinator, 4035213723
- Recruiting
CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0403)
Montreal, Quebec, H1T 2M4
Study Coordinator, 5142523400
- Recruiting
Jewish General Hospital ( Site 0400)
Montreal, Quebec, H3T 1E2
Study Coordinator, 5143408222 x 24572
- Recruiting
The Ottawa Hospital ( Site 0404)
Ottawa, Ontario, K1H 8L6
Study Coordinator, 613 737-7700
- Recruiting
Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0406)
Toronto, Ontario, M5G 2M9
Study Coordinator, 416-946-2827
France5 sites, 4 recruiting
- Completed
Centre Hospitalier de Versailles ( Site 0809)
Le Chesnay, Yvelines, 78150
- Recruiting
Institut Paoli-Calmettes ( Site 0803)
Marseille, Bouches-du-Rhone, 13009
Study Coordinator, +33491223537
- Recruiting
Centre Hospitalier Universitaire de Nice - Hôpital l'Archet ( Site 0810)
Nice, Alpes-Maritimes, 06202
Study Coordinator, +33 4 92 03 57 85
- Recruiting
Hopital Saint Louis ( Site 0805)
Paris, 75010
Study Coordinator, +33142499236
- Recruiting
Centre Hospitalier Lyon-Sud ( Site 0804)
Pierre-Bénite, Auvergne-Rhône-Alpes, 69495
Study Coordinator, +33478864348
Poland5 sites, 2 recruiting
- Completed
Szpitale Pomorskie Sp. z o.o. ( Site 1600)
Gdynia, Pomeranian Voivodeship, 81-519
- Recruiting
Pratia MCM Krakow ( Site 1601)
Krakow, Lesser Poland Voivodeship, 30-727
Study Coordinator, 48 12 2954135
- Completed
Szpital Wojewódzki w Opolu-Hematology Department ( Site 1607)
Opole, Opole Voivodeship, 45-061
- Recruiting
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Kilinka Onkologii I Hematologii ( Site 1608)
Warsaw, Masovian Voivodeship, 02-781
Study Coordinator, +48225462223
- Completed
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu ( Site 1606)
Wroclaw, Lower Silesian Voivodeship, 50-367
Turkey (Türkiye)5 sites, 2 recruiting
- Recruiting
Ankara Universitesi Tip Fakultesi Cebeci Hastanesi ( Site 2400)
Ankara, 06590
Study Coordinator, +903125957099
- Completed
VKV Amerikan Hastanesi ( Site 2403)
Istanbul, 34365
- Recruiting
Sisli Florence Nightingale Hastanesi ( Site 2407)
Istanbul, 34381
Study Coordinator, +90 542 502 50 75
- Active, not recruiting
Dokuz Eylül Üniversitesi-Hematology ( Site 2402)
Izmir, 35340
- Active, not recruiting
Mega Medipol-Hematology ( Site 2406)
Stanbul, Istanbul, 34214
Brazil4 sites, 3 recruiting
- Recruiting
Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0300)
Rio de Janeiro, 20231-050
Study Coordinator, +552132076564
- Recruiting
Hospital das Clinicas FMUSP-Pesquisa Clínica Hematologia ( Site 0303)
São Paulo, São Paulo, 05403-000
Study Coordinator, 551145737543
- Active, not recruiting
BP - A Beneficencia Portuguesa de São Paulo ( Site 0302)
São Paulo, 01321-001
- Recruiting
Hospital Paulistano - Amil Clinical Research ( Site 0311)
São Paulo, 01321-001
Study Coordinator, +551130161340
Denmark4 sites, 2 recruiting
- Recruiting
Aalborg Universitetshospital ( Site 0703)
Aalborg, North Denmark, 9000
Study Coordinator, +45 97660000
- Completed
Aarhus University Hospital ( Site 0702)
Aarhus N, Central Jutland, 8200
- Completed
Odense University Hospital ( Site 0705)
Odense C, Region Syddanmark, 5000
- Recruiting
Sjaellands Universitetshospital Roskilde ( Site 0701)
Roskilde, Region Sjælland, 4000
Study Coordinator, +45 46323200
Germany4 sites, 3 recruiting
- Recruiting
Universitaetsklinikum Koeln ( Site 0901)
Cologne, North Rhine-Westphalia, 50937
Study Coordinator, +4922147897046
- Recruiting
Universitaetsklinikum Carl Gustav Carus ( Site 0902)
Dresden, Saxony, 01307
Study Coordinator, 0049 351 458 5692
- Completed
St. Marien-Krankenhaus Siegen ( Site 0914)
Siegen, North Rhine-Westphalia, 57072
- Recruiting
Universitaetsklinikum Ulm. ( Site 0906)
Ulm, Baden-Wurttemberg, 89081
Study Coordinator, + 49 731 500 45901
Hungary4 sites, 4 recruiting
- Recruiting
Orszagos Onkologiai Intezet ( Site 1200)
Budapest, 1122
Study Coordinator, +3612248600
- Recruiting
Debreceni Egyetem Klinikai Kozpont ( Site 1201)
Debrecen, Hajdú-Bihar, 4032
Study Coordinator, +3652255196
- Recruiting
Szabolcs Szatmár Bereg Vármegyei Oktatókórház ( Site 1206)
Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400
Study Coordinator, +3642599700
- Recruiting
Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar ( Site 1202)
Pécs, Baranya, 7624
Study Coordinator, +3672536000
Romania4 sites, 3 recruiting
- Recruiting
Centrul de Diagnostic si Tratament Oncologic Brasov ( Site 1802)
Brasov, 500052
Study Coordinator, 0729075567
- Recruiting
Spitalul Clinic Colțea ( Site 1805)
Bucharest, Bucharest, 030171
Study Coordinator, 0040213874100
- Recruiting
Institutul Regional de Oncologie Iasi ( Site 1801)
Iași, 700483
Study Coordinator, 40374278811
- Completed
Ovidius Clinical Hospital ( Site 1804)
Ovidiu, Constanța County, 905900
Ukraine4 sites, 2 recruiting
- Active, not recruiting
MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( Site 2509)
Cherkassy, Cherkasy Oblast, 18009
- Completed
Communal non-profit enterprise "Regional clinical hospital o-Hematology Department ( Site 2510)
Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76008
- Recruiting
National Cancer Institute ( Site 2507)
Kyiv, 03022
Study Coordinator, +380672091427
- Recruiting
Instit. of Blood Transfusion Medicine of the National Academy ( Site 2506)
Lviv, Lviv Oblast, 79044
Study Coordinator, +380322352276
Australia3 sites, 2 recruiting
- Recruiting
Box Hill Hospital ( Site 0203)
Box Hill, Victoria, 3128
Study Coordinator, +611300342255
- Recruiting
Sir Charles Gairdner Hospital ( Site 0200)
Nedlands, Western Australia, 6009
Study Coordinator, +61864573333
- Completed
Nepean Hospital-Nepean Cancer Care Centre ( Site 0204)
Sydney, New South Wales, 2747
Czechia2 sites, 2 recruiting
- Recruiting
Fakultní nemocnice Brno Bohunice-Interni hematologicka a onkologicka klinika ( Site 0600)
Brno, Brno-mesto, 625 00
Study Coordinator, +420532233642
- Recruiting
Fakultni nemocnice Hradec Kralove ( Site 0601)
Hradec Králové, 500 05
Study Coordinator, +420495832159
Ireland2 sites, 1 recruiting
- Recruiting
Beaumont Hospital ( Site 2900)
Dublin, Dublin 9
Study Coordinator, +35318092010
- Active, not recruiting
University Hospital Limerick ( Site 2903)
Limerick, V94 F858
South Korea2 sites, 2 recruiting
- Recruiting
Severance Hospital Yonsei University Health System ( Site 2201)
Seoul, 03722
Study Coordinator, +82222281972
- Recruiting
Samsung Medical Center ( Site 2200)
Seoul, 06351
Study Coordinator, +82234106548
Switzerland2 sites, 2 recruiting
- Recruiting
Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 2302)
Bellinzona, Canton Ticino, 6500
Study Coordinator, +41918118540
- Recruiting
Inselspital Bern ( Site 2303)
Bern, Canton of Bern, 3010
Study Coordinator, +41316329023
About this study
Official title: A Phase 2 Study to Evaluate the Efficacy and Safety of MK-1026 in Participants With Hematologic Malignancies
The purpose of this study is to evaluate the safety and efficacy of nemtabrutinib (formerly ARQ 531) in participants with hematologic malignancies of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Richter's transformation, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and Waldenström's macroglobulinemia (WM).
Read the detailed description
This study will be performed in 2 parts: Dose Escalation and Confirmation (Part 1) and Cohort Expansion (Part 2). Following determination of the recommended phase 2 dose (RP2D) in Part 1, the study plans to proceed with Part 2 using 8 disease-specific expansion cohorts (Cohorts A to H).
- Conditions
- Hematologic Malignancies, Waldenstroms Macroglobulinaemia, Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukaemia
- Being tested
- Nemtabrutinib
- Medical subject headings
- Hematologic Neoplasms, Waldenstrom Macroglobulinemia, Lymphoma, Non-Hodgkin, Leukemia, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NemtabrutinibDrug
Also called ARQ 531, MK-1026
Nemtabrutinib tablets administered orally QD.
| Study group | Role | What they receive |
|---|---|---|
| Nemtabrutinib | Experimental | Participants receive nemtabrutinib orally once daily (QD) until progressive disease (PD) or discontinuation. Receives: Drug: Nemtabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of participants experiencing dose-limiting toxicities (DLTs)
DLTs will be defined as toxicities observed during the first 2 cycles (8 weeks) of Part 1 and include: Grade ≥3 nonhematologic toxicity (except Grade 3 nausea, vomiting, diarrhea, rash, fatigue, and uncontrolled hypertension which will not be considered a DLT unless lasting ≥72 hours despite optimal supportive care); Grade 4 hematologic toxicity lasting >7 days (except Grade 3 lymphocytosis, Grade 4 platelet count decreased of any duration, or Grade 3 platelet count decreased if associated with bleeding); any Grade 3 or Grade 4 nonhematologic laboratory abnormality if values result in drug-induced liver injury, or medical intervention is required, or the abnormality leads to hospitalization, or the abnormality persists for >1 week (with exceptions); missing >25% of nemtabrutinib doses as a result of drug-related adverse events (AEs) during the first 2 cycles (8 weeks); Grade 5 toxicity.
Measured: Up to ~56 days (Cycles 1-2, cycle = 28 days)
Part 1: Number of participants experiencing adverse events (AEs)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported for Part 1.
Measured: Up to ~71 months
Part 1: Number of participants discontinuing study treatment due to AEs
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study treatment due to an AE will be reported for Part 1.
Measured: Up to ~42 months
Part 2: Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria 2018 as assessed by independent central review (ICR)
ORR per iwCLL 2018 criteria is defined as the percentage of participants achieving a complete response (CR), complete response with incomplete bone marrow recovery (CRi), nodular partial response (nPR), or partial response (PR). CR is defined as meeting the following criteria: no lymph nodes >1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with hypocellular bone marrow. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or ≥50% increase from screening, hemoglobin >11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.
Measured: Up to ~61 months
Part 2: ORR per Lugano criteria 2014 as assessed by ICR
ORR per Lugano criteria 2014 is defined as the percentage of participants achieving a CR or PR. CR defined as EITHER CR by imaging (computed tomography [CT]): all lymph nodes normal (none ≥15 mm) and normal liver and spleen OR complete metabolic response (CMR): score of 1, 2 or 3 on the 5-point scale assessing fluorodeoxyglucose (FDG) metabolic activity in lymphomatous lesions (ranging from 1=no uptake above background to 5=uptake markedly higher than liver) AND bone marrow (BM) normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in the sum of the product of diameters [SPD] of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR Partial Metabolic Response (PMR) with score of 4 or 5 on the FDG 5-point scale (with no new lesions) and decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.
Measured: Up to ~61 months
Part 2: ORR per International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria 2014 as assessed by ICR
ORR per IWWM criteria 2014 is defined as the percentage of participants achieving a CR, very good partial response (VGPR), or PR. CR is defined as all lymph nodes are normal in size (none ≥15 mm), liver and spleen normal in size, serum immunoglobulin M (IgM) values in the normal range, disappearance of monoclonal protein by immunofixation (confirmation needed with a second immunofixation at any subsequent timepoint), and no histological evidence of BM involvement. VGPR is defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline), ≥50% decrease from baseline in the abnormal portion of the spleen (if previously abnormal), and ≥90% decrease from baseline in serum IgM, or serum IgM values in normal range. PR is defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline), ≥50% decrease from baseline in serum IgM, and ≥50% decrease from baseline in the abnormal portion of the spleen (if previously abnormal).
Measured: Up to ~71 months
Secondary outcomes (13)
Part 1: Area Under the Curve (AUC) of Nemtabrutinib
Blood samples will be obtained at designated time points during Part 1 for the assessment of nemtabrutinib AUC (Day 1 of Cycles 1 and 2: Pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2, 4, and 6 hours post-dose [up to ~57 days]). Each cycle is 28 days.
Measured: At designated time points (up to ~57 days)
Part 1: Minimum Concentration (Cmin) of Nemtabrutinib
Blood samples will be obtained at designated time points during Part 1 for the assessment of nemtabrutinib Cmin (Day 1 of Cycles 1 and 2: Pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2, 4, and 6 hours post-dose [up to ~57 days]). Each cycle is 28 days.
Measured: At designated time points (up to ~57 days)
Part 1: Maximum Concentration (Cmax) of Nemtabrutinib
Blood samples will be obtained at designated time points during Part 1 for the assessment of nemtabrutinib Cmax (Day 1 of Cycles 1 and 2: Pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2, 4, and 6 hours post-dose [up to ~57 days]). Each cycle is 28 days.
Measured: At designated time points (up to ~57 days)
Part 1: ORR per iwCLL criteria 2018 as assessed by ICR
ORR per iwCLL 2018 criteria is defined as the percentage of participants achieving a CR, CRi, nPR, or PR. CR is defined as meeting the following criteria: no lymph nodes >1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with hypocellular bone marrow. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or ≥50% increase from screening, hemoglobin >11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.
Measured: Up to ~71 months
Part 1: Duration of Response (DOR) per iwCLL criteria 2018 as assessed by ICR
For participants with CR, CRi, nPR, or PR per iwCLL 2018 criteria, DOR is defined as the time from the first documented evidence of objective response until PD or death due to any cause, whichever occurs first. CR is defined as meeting the following criteria: no lymph nodes >1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with hypocellular bone marrow. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or ≥50% increase from screening, hemoglobin >11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.
Measured: Up to ~71 months
Part 2: Number of participants experiencing AEs
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported for Part 2.
Measured: Up to ~61 months
Part 2: Number of participants discontinuing study treatment due to AEs
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study treatment due to an AE will be reported for Part 2.
Measured: Up to ~42 months
Part 2: AUC of Nemtabrutinib
Blood samples will be obtained at designated time points during Part 2 for the assessment of nemtabrutinib AUC (Day 1 of Cycles 1, 2, and 3: Pre-dose, 2, 4, 6, hours post-dose [up to ~57 days]). Each cycle is 28 days.
Measured: At designated time points (up to ~57 days)
Part 2: Cmin of Nemtabrutinib
Blood samples will be obtained at designated time points during Part 2 for the assessment of nemtabrutinib Cmin (Day 1 of Cycles 1, 2, and 3: Pre-dose, 2, 4, 6, hours post-dose [up to ~57 days]). Each cycle is 28 days.
Measured: At designated time points (up to ~57 days)
Part 2: Cmax of Nemtabrutinib
Blood samples will be obtained at designated time points during Part 2 for the assessment of nemtabrutinib Cmax (Day 1 of Cycles 1, 2, and 3: Pre-dose, 2, 4, 6, hours post-dose [up to ~57 days]). Each cycle is 28 days.
Measured: At designated time points (up to ~57 days)
Part 2: DOR per iwCLL criteria 2018 as assessed by ICR
For participants with CR, CRi, nPR, or PR per iwCLL 2018 criteria, DOR is defined as the time from the first documented evidence of objective response until disease progression or death due to any cause, whichever occurs first. CR is defined as meeting the following criteria: no lymph nodes >1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with hypocellular bone marrow. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or ≥50% increase from screening, hemoglobin >11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.
Measured: Up to ~61 months
Part 2: DOR per Lugano criteria 2014 as assessed by ICR
For participants with CR or PR per Lugano criteria 2014, DOR is defined as the time from the first documented evidence of objective response until PD or death due to any cause, whichever occurs first. CR defined as EITHER CR by imaging (CT): all lymph nodes normal (none ≥15 mm) and normal liver and spleen OR CMR: score of 1, 2 or 3 on the 5-point scale assessing FDG metabolic activity in lymphomatous lesions (ranging from 1=no uptake above background to 5=uptake markedly higher than liver and/or new lesions) AND BM normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in the SPD of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR PMR with score of 4 or 5 on the FDG 5-point scale (with no new lesions) and decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.
Measured: Up to ~61 months
Part 2: DOR per IWWM criteria 2014 as assessed by ICR
For participants with CR, VGPR, or PR per IWWM criteria 2014, DOR defined as the time from first documented evidence of objective response until PD or death due to any cause, whichever occurs first. CR defined as all lymph nodes normal in size (none ≥15 mm), liver and spleen normal in size, serum IgM values in normal range, disappearance of monoclonal protein by immunofixation (confirmation needed with second immunofixation at any subsequent timepoint), and no histological evidence of BM involvement. VGPR defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline), ≥50% decrease from baseline in abnormal portion of the spleen (if previously abnormal), and ≥90% decrease from baseline in serum IgM, or serum IgM values in normal range. PR is defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline), ≥50% decrease from baseline in serum IgM, and ≥50% decrease from baseline in abnormal portion of the spleen (if previously abnormal).
Measured: Up to ~61 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2021
- Study start5 Apr 2021
- Primary completion4 Jan 2029 (estimated)
- Study completion4 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 490 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04728893
- Sponsor's protocol ID
- 1026-003
- Other IDs
- MK-1026-003, 2023-504931-42-00, U1111-1290-4004, 2020-002324-36, 2023
- Status last verified
- Oct 2026
- First submitted
- 25 Jan 2021
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf