A Study of NX-5948 in Adults With CLL/SLL Previously Treated With a Bruton's Tyrosine Kinase Inhibitor and a B-cell Lymphoma-2 Inhibitor (DAYBreak CLL-201)

Official title

A Single-arm, Phase 2, Open-label, Multicenter Study to Evaluate NX-5948 in Adults With Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Previously Exposed to a Bruton's Tyrosine Kinase Inhibitor (BTKi) and a B-cell Lymphoma-2 Inhibitor (BCL-2i)

Overview

This is a study for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received treatment with a BTK inhibitor (covalent and non-covalent) and a BCL-2 inhibitor. The main purpose of this study is to test if NX-5948 (bexobrutideg) works to treat patients with CLL/SLL. Participation could last up to 5 years, and possibly longer, if the disease does not progress.

Detailed description

The main purpose of this study is to test if NX-5948 works to treat patients with R/R CLL/SLL. NX-5948 is a BTK degrader and works by destroying the BTK protein to stop all its actions. This is different from a BTK inhibitor which works by blocking only the kinase action of BTK. This study aims to answer these questions:

* How well does NX-5948 work to treat patients who have previously received a BTK inhibitor and a BCL-2 inhibitor? * How safe is NX-5948 and can patients take NX-5948 as long as they need to? * What is the amount of NX-5948 in the bloodstream over time when given to patients with CLL/SLL?

All patients in the study will receive NX-5948 orally until their cancer gets worse or if there are other reasons to stop taking NX-5948. Patients will have their cancer and other health check-ups regularly while they are taking NX-5948. If a patient's cancer has not gotten worse and they stop taking NX-5948, they will continue to have cancer check-ups until their cancer gets worse.

Interventions

• Drug NX-5948
  Oral dose administered once daily. NX-5948 will be given in continuous 28-day cycles.

Primary outcome measures

• Objective response rate without partial response with lymphocytosis (PR-L) as determined by an Independent Review Committee (IRC) [Time frame: Up to approximately 5 years]

Secondary outcome measures (12)

• Objective response rate with PR-L as determined by IRC [Time frame: Up to approximately 5 years]
• Objective response rate with and without PR-L as determined by investigator [Time frame: Up to approximately 5 years]
• Duration of response as determined by IRC and by investigator [Time frame: Up to approximately 5 years]
• Progression-free survival as determined by IRC and by investigator [Time frame: Up to approximately 5 years]
• Complete response rate as determined by IRC and by investigator [Time frame: Up to approximately 5 years]
• Time to response as determined by IRC and by investigator [Time frame: Up to approximately 5 years]
• Overall survival [Time frame: Up to approximately 5 years]
• Number of participants with treatment-emergent adverse events (TEAEs), Grade 3 or higher TEAEs, serious adverse events, and TEAEs leading to study drug discontinuation [Time frame: Up to approximately 3 years]
• Number of participants with clinically significant changes from baseline in laboratory parameters [Time frame: Up to approximately 3 years]
• Number of participants with clinically significant changes from baseline in vital signs [Time frame: Up to approximately 3 years]
• Pharmacokinetic profile of NX-5948 [Time frame: Up to approximately 1 year]
• Change from baseline in Global Health Status/Quality of Life on the European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30) [Time frame: Baseline and up to approximately 5 years]

Eligibility criteria

Inclusion criteria

• Age: ≥ 18 years
• Confirmed relapsed/refractory CLL/SLL that meets iwCLL criteria for diagnosis and systemic treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Must have received a covalent BTK inhibitor (BTKi), a non-covalent BTKi, and a BCL-2 inhibitor either in separate lines of therapy or in combination; a line of therapy is considered 2 or more consecutive cycles of a systemic anti-CLL/SLL regimen
• Participants with SLL must have measurable disease by radiographic assessment
• Adequate organ and bone marrow function
• Must sign an informed consent form indicating that he or she understands the purpose of the procedures required for the study and is willing to participate

Exclusion criteria

• Known or suspected prolymphocytic leukemia or Richter's transformation before entering study
• Investigational agent or anticancer therapy within 5 half-lives or 14 days (whichever is shorter) before planned start of study drug

• Antibody therapy must stop at least 4 weeks before the first dose of study drug
• No other systemic anticancer therapy is allowed at the same time as this study; exception: continuation of hormonal therapy for breast and prostate cancer is allowed, if they are not on the list of prohibited concomitant medications in this study
• Palliative limited-field radiotherapy within 7 days of the first dose of study or broad field radiotherapy within 28 days of first dose of study drug
• Use of systemic corticosteroids >20 mg/day prednisone or equivalent within the 7 days before start of study drug except for those used as premedication for radio diagnostic contrast
• Use of systemic immunosuppressive drugs other than systemic corticosteroids within 60 days before the first dose of study drug
• Previously treated with a BTK degrader
• Previous chimeric antigen receptor (CAR) T-cell therapy or allogeneic or autologous hematopoietic cell transplant within the past 90 days prior to enrollment
• Thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), stroke, or intracranial hemorrhage within 6 months of planned start of study drug

Note: Other Inclusion/Exclusion criteria may apply as defined in the protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 23 centers

• City of Hope — Duarte
• Cedars-Sinai Medical Center — Los Angeles
• Scripps Health — San Diego
• Colorado Blood Institute — Denver
• University of Miami — Coral Gables
• Florida Cancer Specialists — Sarasota
• Fort Wayne Oncology and Hematology — Fort Wayne
• Hematology Oncology of Indiana — Indianapolis
• … and 15 more centers

Italy · 4 centers

• Azienda Ospedaliero-Universitaria di Alessandria SS. Antonio e Biagio e Cesare Arrigo — Alessandria
• IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola — Bologna
• Ospedale San Raffaele S.r.l. — Milan
• AUSL della Romagna UO Ematologia — Ravenna

Poland · 4 centers

• Pratia Hematologia Sp. z o.o. — Katowice
• Pratia S.A. — Krakow
• Aidport Sp. z o.o. — Skorzewo
• Pratia Warszawa / Pratia MTZ — Warsaw

United Kingdom · 3 centers

• Oxford University Hospitals NHS Foundation Trust — Headington
• The Royal Marsden NHS Foundation Trust — London
• The Christie NHS Foundation Trust — Manchester

France · 1 center

• CHU de Nantes — Nantes

Identifiers

NCT: NCT07221500 · NX-5948-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗