A Phase 1, Dose Escalation, and Cohort Expansion Study Evaluating NX-5948, a Bruton's Tyrosine Kinase (BTK) Degrader, in Adults With Relapsed/Refractory B-cell Malignancies
Status: Recruiting
Location: See all (61) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1
SUMMARY
This is a first-in-human Phase 1a/1b multicenter, open-label study designed to evaluate the safety and anti-cancer activity of NX-5948 in patients with advanced B-cell malignancies.
Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:
• Age ≥18 years
• Patients in Phase 1a (Dose Escalation) must have histologically confirmed R/R CLL, SLL, DLBCL (subgroups include Richter-transformed DLBCL, germinal center B-cell type, activated B-cell type, high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements, high-grade B-cell lymphomas NOS), FL, MCL, MZL (subtypes include EMZL, MALT, NMZL, SMZL), WM, or PCNSL.
• Patients in Phase 1a must meet the following:
• o For non-PCNSL indications, received at least 2 prior lines of therapy and have no other available therapies known to provide clinical benefit. For PCNSL, received at least 1 prior line of therapy
• Patients in Phase 1b (Safety and Cohort Expansion) must have 1 of the following histologically documented B-cell malignancies, must meet criteria for systemic treatment, and must have received prior therapies and/or molecular features based on details described for each cohort: CLL or SLL, DLBCL, MCL, FL, MZL, WM, or PCNSL/SCNSL.
• Measurable disease per response criteria specific to the malignancy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (0-2 for patients with PCNSL and secondary CNS involvement).
• Adequate organ and bone marrow function
Locations
United States
California
City of Hope
RECRUITING
Duarte
University of California, San Francisco
RECRUITING
San Francisco
Colorado
Colorado Blood Cancer Institute
RECRUITING
Denver
Connecticut
Yale Cancer Center
RECRUITING
New Haven
Florida
University of Miami
RECRUITING
Miami
Florida Cancer Specialists
RECRUITING
Sarasota
Georgia
Winship Cancer Institute of Emory University
RECRUITING
Atlanta
Illinois
Northwestern University
RECRUITING
Chicago
Maryland
National Institute of Health
RECRUITING
Bethesda
North Carolina
Duke University Medical Center
RECRUITING
Durham
New York
Cayuga Medical Center
COMPLETED
Ithaca
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
Ohio
University of Cincinnati Medical Center
RECRUITING
Cincinnati
Cleveland Clinic
RECRUITING
Cleveland
Pennsylvania
University of Pennsylvania, Abramson Cancer Center
RECRUITING
Philadelphia
Texas
MD Anderson Cancer Center
RECRUITING
Houston
Utah
Huntsman Cancer Institute
RECRUITING
Salt Lake City
Wisconsin
Medical College of Wisconsin
RECRUITING
Milwaukee
Other Locations
France
CHU Angers
RECRUITING
Angers
Hôpital Avicenne
RECRUITING
Bobigny
CHU de Nantes
RECRUITING
Nantes
CHU Bordeaux
RECRUITING
Pessac
CHU de Poitiers
RECRUITING
Poitiers
Institut Curie-Site Saint-Cloud
RECRUITING
Saint-cloud
CHRU de Nancy
RECRUITING
Vandœuvre-lès-nancy
Italy
IRCCS - AOU di Bologna
RECRUITING
Bologna
ASST Spedali Civili Brescia
RECRUITING
Brescia
IRCCS Ospedale San Raffaele
RECRUITING
Milan
IRCCS Ospedale San Raffaele - Università Vita-Salute San Raffaele di Milano
RECRUITING
Milan
Netherlands
University Medical Center Groningen
RECRUITING
Groningen
Radboud University Medical Center
RECRUITING
Nijmegen
Erasmus MC
RECRUITING
Rotterdam
University Medical Center Utrecht
RECRUITING
Utrecht
Poland
Pratia Onkologia Katowice
RECRUITING
Katowice
Pratia MCM
RECRUITING
Krakow
Medical University of Lublin
RECRUITING
Lublin
AidPort sp. Zo.o
RECRUITING
Skórzewo
National Institute of Oncology Warszawa
RECRUITING
Warsaw
Pratia MTZ
RECRUITING
Warsaw
University Clinical Hostpital in Wroclaw
RECRUITING
Wroclaw
Spain
Hospital Clínic de Barcelona
RECRUITING
Barcelona
Hospital Universitari Vall d'Hebron
RECRUITING
Barcelona
Hospital Universitario de Cabuenes
RECRUITING
Gijón
Hospital Fundación Jimenez Díaz - START Madrid
RECRUITING
Madrid
Hospital Ramón y Cajal
RECRUITING
Madrid
Switzerland
Universitätsspital Basel
RECRUITING
Basel
Istituto Oncologico della Svizzera Italiana
RECRUITING
Bellinzona
Inselspital - Universitatsklinik Bern
RECRUITING
Bern
Hôpitaux Universitaires de Genève
RECRUITING
Geneva
Kantonsspital St.Gallen
RECRUITING
Sankt Gallen
University Hospital Zurich
RECRUITING
Zurich
United Kingdom
The Beatson WOS Cancer Center
RECRUITING
Glasgow
St. James Hospital
RECRUITING
Leeds
Clatterbridge Cancer Center NHS Foundation Trust
RECRUITING
Liverpool
Sarah Cannon Research Institute UK
RECRUITING
London
St. Bartholomew's Hospital, Barts NHS Trust
RECRUITING
London
The Christie NHS Foundation Trust
RECRUITING
Manchester
Oxford University Hospitals NHS Foundation Trust
RECRUITING
Oxford
University Hospitals Plymouth NHS Trust
RECRUITING
Plymouth
University Hospital Southampton NHS Foundation Trust
RECRUITING
Southampton
Royal Marsden NHS Foundation Trust
RECRUITING
Sutton
Contact Information
Primary
Additional Site Contact Information
NX5948301@nurixtx.com
+1 (415) 417-3441
Time Frame
Start Date: 2022-04-13
Estimated Completion Date: 2028-01
Participants
Target number of participants: 572
Treatments
Experimental: Phase 1a Dose Escalation
Multiple dose levels of NX-5948 to be evaluated; determination of Maximum Tolerated Dose/Phase 1b recommended dose(s)
Experimental: Phase 1b Part 1 Cohort 1 in CLL or SLL with prior BTKi and BCL2i
CLL or SLL with prior exposure to both a Bruton's tyrosine kinase inhibitor (BTKi) and BCL-2 inhibitor, unless previously deemed ineligible for a BCL-2i. Patients enrolled in CLL/SLL arm will be randomized to one of two dose levels.
Experimental: Phase 1b Part 1 Cohort 2 in CLL/SLL with non-C481S BTK mutations
Prior exposure to both BTKi and BCL-2i (unless deemed ineligible for BCL-2i by Investigator at the time of study enrollment) and documented BTK mutation other than C481S within 6 months prior to study entry
Experimental: Phase 1b Part 1 Cohort 3 in CLL/SLL with prior non-covalent BTKi
CLL/SLL with prior exposure to ncBTKi and are BCL-2i naïve.
Experimental: Phase 1b Part 1 Cohort 4 in CLL/SLL with TP53 or 17p deletion, 2L, prior BTKi
Patients with documented TP53 mutation or 17p deletion and 1 prior line of therapy that included a BTKi and are BCL-2i naïve.
Experimental: Phase 1b Part 1 Cohort 5 in CLL/SLL with 2L+, prior BTKi
Patients with at least 1 prior line of therapy that included a BTKi and are BCL-2i naïve.
Experimental: Phase 1b Part 1 Cohort 6 in MCL
Non-blastoid MCL with prior exposure to a BTKi and an anti-CD20 monoclonal antibody (mAb)-based chemoimmunotherapy regimen
Experimental: Phase 1b Part 1 Cohort 7 in MZL
MZL (EMZL, MALT, NMZL, SMZL) with prior exposure to an anti-CD20 mAb-based chemo-immunotherapy regimen and an additional line of therapy
Experimental: Phase 1b Part 1 Cohort 8 in WM (3L+)
WM with prior exposure to a BTKi and at least an additional line of therapy
Experimental: Phase 1b Part 1 Cohort 9 in WM (2L)
WM following upfront therapy with a BTKi
Experimental: Phase 1b Part 1 Cohort 10 in DLBCL
DLBCL which transformed from indolent lymphoma or Richters transformation with prior exposure to an anthracycline (unless previously deemed ineligible to receive), an anti-CD20 mAb-based chemoimmunotherapy regimen, and an additional line of therapy
Experimental: Phase 1b Part 1 Cohort 11 in FL
FL (grade 1-3a) with prior exposure to an anti-CD20 mAb-based chemoimmunotherapy regimen and an additional line of therapy
Experimental: Phase 1b Part 1 Cohort 12 in PCNSL/SCNSL
PCNSL following at least 1 prior line of therapy that included a BTKi (2L+) or following 2 or more prior lines of therapy (3L+), or SCNSL patients meeting criteria for a non-CLL/SLL cohort enrolling that disease with secondary CNS involvement of lymphoma
Experimental: Phase 1b Part 1 Cohort 13 in PCNSL
PCNSL following upfront therapy and with no prior exposure to a BTKi (2L).
Experimental: Phase 1b Part 2 in CLL or SLL with prior BTKi and BCL-2i
CLL or SLL with prior exposure to both a Bruton's tyrosine kinase inhibitor (BTKi) and BCL-2 inhibitor
Experimental: Phase 1b Part 1 Cohort 14 in first-line WM
Treatment-naïve WM deemed unfit for chemoimmunotherapy
Experimental: Phase 1b Part 1 Cohort 15 in BTKi-naive CLL/SLL
First-line (1L) or second-line+ (2L)+ CLL/SLL with no prior exposure to a BTKi
Experimental: Phase 1b Part 1 Cohort 16 in CLL/SLL with secondary warm autoimmune hemolytic anemia (wAIHA)
BTKi-exposed R/R CLL or SLL with secondary wAIHA
Experimental: Phase 1b Part 1 Cohort 17 in CLL/SLL with CNS involvement
BTKi-exposed R/R CLL or SLL with CNS involvement
Related Therapeutic Areas
Sponsors
Leads: Nurix Therapeutics, Inc.