NX-5948-301 The treatment of adult patients with a B-cell lymphoma who have a relapse or do not respond to another treatment, with the active substance NX-5948, an inhibitor of the enzyme Bruton tyrosine kinase. A Phase I study with varying dosages.
Zusammenfassung der Studie
This study aims to determine the effect of the investigational drug NX-5948 in patients with B-cell lymphoma or B-cell leukemia. This is an international study conducted at multiple study centers in countries of the European Union, Switzerland, the United Kingdom, and the USA. A total of 532 individuals are expected to participate in the study. The study consists of three parts: 1. In the first part, the dose of the investigational substance is gradually increased (dose escalation). 2. In the second part, the safety and efficacy of selected optimal dosages are investigated (safety dose expansion). 3. In the third part, the safety and efficacy of selected dosages are examined in individuals with CLL/SLL (cohort expansion). This study includes patients suffering from a B-cell lymphoma or B-cell leukemia who have not responded to prior therapy (therapy-resistant lymphoma / therapy-resistant leukemia) or who have experienced a relapse after a period of improvement (relapse / recurrence). The study investigates whether different dosages of the investigational substance NX-5948 are safe and well-tolerated and whether NX-5948 is effective in B-cell lymphomas. Participation in this study occurs in four consecutive steps: 1. Screening: Various examinations are conducted on patients to determine their eligibility for participation in the study. 2. Treatment: Patients take the investigational substance NX-5948 at regular intervals and are monitored regularly. 3. Safety observation: After taking the last dose of NX-5948, patients will be followed up three times within 30 days. 4. Long-term follow-up for a maximum of five years.
(BASEC)
Untersuchte Intervention
Treatment
The study treatment is divided into so-called cycles. Each cycle lasts 28 days. Each appointment during the study is precisely defined by the designation of cycle and day (example: 'Cycle 3, Day 1' means 'The first day in the third cycle').
Patients receive capsules containing the investigational substance on the first day of each cycle. The principal investigator will explain how the capsules should be taken. Most patients need to take one capsule daily; some need to take two capsules per day during the second part of the study. For once-daily dosing, nothing should be eaten at least two hours before and two hours after taking the capsule. For twice-daily dosing, nothing should be eaten at least eight hours before the morning dose and two hours after. On the first days of Cycle 1 and Cycle 2, patients should not eat at least eight hours before and two hours after taking the investigational substance. However, they may drink water during fasting. Patients who forget to fast are asked to report what they ate and drank in the eight hours before and two hours after taking the investigational substance.
For each treatment cycle, patients receive a medication diary. They record daily how many capsules of the investigational substance they took and when. They should also note if they missed a dose or experienced side effects such as vomiting. Patients must bring the medication diary to each appointment with the principal investigator.
In the first two months of the study (Cycles 1 and 2), each participant has many appointments. The appointments on the first days of these two cycles last at least eight hours. Health status is closely monitored. In Cycles 1 and 2, appointments must also be kept on the second day and then weekly to ensure that no unexpected side effects occur.
During Cycles 3 and 4, patients still have appointments on the first and 15th days. From Cycle 5 onwards, patients only need to come for an appointment on the first day of a cycle.
Various examinations are conducted during the appointments. If the disease improves or progresses during the study, further examinations may be necessary. The principal investigator will inform about any additional examinations in such cases.
Patients may need to take medications during the study to prevent certain side effects or diseases.
During the study, patients are not allowed to take certain medications and eat specific foods (e.g., grapefruits). The principal investigator will inform which medications and foods are involved.
Since the effect of the investigational substance is not precisely known, it is important for the patient to inform the principal investigator about any new symptoms that arise.
Safety observation
After completing the intake of the investigational substance, patients will be examined again within three days after the last dose. Further follow-up therapy will occur approximately 15 and 30 days after the last dose. If patients start another cancer therapy before the appointments on the 15th or 30th days after the last dose, these follow-up appointments will be omitted. These patients will then be monitored as part of the long-term follow-up.
Long-term follow-up
After the safety observation is completed, patients will be contacted by the study team every three months. The researchers will ask them about their health, the course of their disease, and whether they may have received new lymphoma treatments. These interviews will be conducted by phone or during a personal appointment at the clinic.
(BASEC)
Untersuchte Krankheit(en)
B-cell lymphoma
(BASEC)
- Patients must be at least 18 years old. - Patients must have a B-cell lymphoma or B-cell leukemia. They must meet the criteria for systemic therapy and have a history and/or molecular characteristics that are described for their assigned cohort. - Patients must have measurable disease according to the response criteria for malignant tumors. (BASEC)
Ausschlusskriterien
- Known or suspected active prolymphocytic leukemia or Richter transformation into Hodgkin lymphoma prior to enrollment in the study. - Prior treatment for the investigated indication, including radiation therapy within 2 weeks before the planned start of the study medication; prior systemic chemotherapy within 2 weeks before the planned start of the study medication; prior mAb therapy within 4 weeks before the planned start of the study medication; prior small molecule therapy within 5 half-lives or 2 weeks before the planned start of the study medication. - Active, uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia. - Inability to swallow capsules or malabsorption syndrome, diseases or procedures that significantly impair gastrointestinal function and may affect the administration, absorption, or metabolism of the study medication. (BASEC)
Studienstandort
Basel, Bellinzona, Bern, Genf, St Gallen, Zürich
(BASEC)
Sponsor
Nurix Therapeutics Inc., San Francisco (CA), USA Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK), Bern
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Julia Decoudre
+4131 389 91 91
trials@cluttersakk.chSchweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK), Bern
(BASEC)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Tessin
(BASEC)
Datum der Bewilligung durch die Ethikkommission
23.01.2025
(BASEC)
ICTRP Studien-ID
NCT05131022 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
NX-5948-301 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 (BASEC)
Wissenschaftlicher Titel
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 (ICTRP)
Öffentlicher Titel
A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies (ICTRP)
Untersuchte Krankheit(en)
Chronic Lymphocytic Leukemia (CLL)Small Lymphocytic Lymphoma (SLL)Diffuse Large B Cell Lymphoma (DLBCL)Follicular Lymphoma (FL)Mantle Cell Lymphoma (MCL)Marginal Zone Lymphoma (MZL)Waldenstrom Macroglobulinemia (WM)Primary Central Nervous System Lymphoma (PCNSL)Secondary Central Nervous System Lymphoma (SCNSL) (ICTRP)
Untersuchte Intervention
Drug: NX-5948 (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Ein-/Ausschlusskriterien
Key Inclusion Criteria:
- 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
Key Exclusion Criteria:
- Known or suspected active prolymphocytic leukemia or Richter's transformation to
Hodgkin's lymphoma prior to study enrollment
- Prior treatment for the indication under study for anti-cancer intent that includes:
1. Radiotherapy within 2 weeks of planned start of study drug (excluding limited
palliative radiation).
2. Prior systemic chemotherapy within 2 weeks of planned start of study drug.
3. Prior monoclonal antibody therapy within 4 weeks of planned start of study
drug, except for patients enrolling in Cohort 16 (CLL with secondary wAIHA)
where a 16-week washout period is required.
4. Prior small molecule therapy within 2 weeks or 5 half-lives (whichever is
shorter) of planned start of study drug.
5. Autologous or allogeneic stem cell transplant within 100 days prior to planned
start of study drug.
6. Chimeric antigen receptor (CAR) T-cell therapy within 100 days prior to start
of study drug (within 60 days prior to start of study drug for Phase 1b).
7. Use of systemic corticosteroids outside of dosing limits described below and
within 7 days prior to initiation of study treatment excepting those used as
prophylaxis for radio diagnostic contrast. Patients with PCNSL/SCNSL: no
greater than 40 mg/day prednisone, or equivalent. Patients with PCNSL/SCNSL
using greater than 20 mg/day prednisone, or equivalent, must be clinically
stable at that dose for 7 days. All other diagnoses: no greater than 20 mg/day
prednisone or equivalent.
8. Use of systemic immunosuppressive drugs other than systemic corticosteroids for
any medical condition within 60 days prior to first dose of study drug
9. Previously treated with a BTK degrader
- Active, uncontrolled autoimmune hemolytic anemia (except for patients enrolling in
Cohort 16) or active, uncontrolled autoimmune thrombocytopenia.
- Patient has any of the following within 6 months of planned start of study drug:
1. Myocardial infarction, unstable angina, unstable symptomatic ischemic heart
disease, or placement of a coronary arterial stent
2. Uncontrolled atrial fibrillation or other clinically significant arrhythmias,
conduction abnormalities, or New York Heart Association (NYHA) class III or IV
heart failure
3. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or
symptomatic cerebrovascular events), stroke, or intracranial hemorrhage
4. Any other significant cardiac condition (e.g., pericardial effusion,
restrictive cardiomyopathy, severe untreated valvular stenosis, severe
congenital heart disease, or persistent uncontrolled hypertension defined as
systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg
despite optimal medical management)
- Bleeding diathesis, or other known risk for acute blood loss.
- History of Grade = 2 hemorrhage within 28 days of planned start of study drug.
- Active known concurrent malignancy or malignancy other than the one under study
within the past 3 years. (Exceptions include, but are not limited to, patients with
more recent history of basal or squamous cell skin cancer, superficial bladder
cancer, or carcinoma in situ of the cervix or breast may enroll if they have
undergone curative therapy and have no evidence of disease). (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Number of participants with protocol specified dose-limiting toxicities;To establish the maximum tolerated dose and/or recommended Phase 1b dose(s);To evaluate the anti-tumor activity of NX-5948 in the dose levels selected for Phase 1b safety expansion based on overall response rate (ORR) as assessed by Investigator;Number of participants with treatment-emergent adverse events (TEAEs); Grade 3, 4, 5 TEAEs, serious adverse events (SAEs), TEAEs leading to study drug discontinuation, deaths due to TEAEs, and all deaths;To further evaluate the anti-tumor activity of NX-5948 in patients with CLL/SLL at the dose identified in Phase 1b Part 1 based on overall response rate (ORR) as assessed by Investigator (ICTRP)
Pharmacokinetic (PK) profile of NX-5948: Maximum Serum Concentration;Pharmacodynamic (PD) profile of NX-5948: Changes from baseline of BTK levels in B-cells;Complete response (CR) rate / CR with incomplete marrow recovery as assessed by the Investigator;Duration of response (DOR) as assessed by the Investigator;Progression-free survival (PFS) as assessed by the Investigator;Time to next therapy;Number of participants with treatment-emergent adverse events (TEAEs); Grade 3, 4, 5 TEAEs, serious adverse events (SAEs), TEAEs leading to study drug discontinuation, deaths due to TEAEs, and all deaths (ICTRP)
Registrierungsdatum
12.11.2021 (ICTRP)
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Paula O'Connor, MDAdditional Site Contact Information, NX5948301@nurixtx.com, +1 (415) 417-3441, Nurix Therapeutics, Inc. (ICTRP)
Sekundäre IDs
2023-510541-25-00, 2021-003125-29, NX-5948-301 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT05131022 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar