Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
NX-5948 · 6 trials · 13 indications
Time from randomization to disease progression per 2018 International Workshop on CLL (iwCLL) or death due to any cause, whichever is earlier
Percentage of participants with best overall response of complete response (CR)/CR with incomplete marrow recovery (CRi), partial response (PR), or nodular PR, as assessed per 2018 iwCLL guidelines
The percentage of participants with response as determined according to 2018 International Workshop on CLL (iwCLL) guidelines. Response will include complete response (CR)/CR with incomplete marrow recovery (CRi), partial response (PR), and nodular PR.
NX-5948 administered as a tablet or capsule under fasting and fed conditions; with and without esomeprazole, famotidine, or quinidine
NX-5948 administered as a tablet or capsule under fasting and fed conditions; with and without esomeprazole, famotidine, or quinidine
NX-5948 administered as a tablet or capsule under fasting and fed conditions; with and without esomeprazole, famotidine, or quinidine
Midazolam, rosuvastatin, or digoxin administered with and without NX-5948
Midazolam, rosuvastatin, or digoxin administered with and without NX-5948
Midazolam, rosuvastatin, or digoxin administered with and without NX-5948
Characterize the Area Under the Curve (AUC0-inf), Half-life (T1/2) of a single IV dose of NX-5948 in healthy adult male subjects.
Identify major metabolite and its AUC in plasma following a single oral dose of \[14C\]-NX-5948 in healthy adult male subjects.
Determine the absolute bioavailability (ABA) of an oral formulation of \[NX-5948C\]- in healthy adult male subjects.
Determine the recovery of total radioactivity (TRA; mass balance) as a percentage of the administered dose after a single oral dose of \[14C\]-NX-5948 in healthy adult male subjects.
Characterize whole blood to plasma ratio for TRA following a single oral dose of \[14C\]-NX-5948 in healthy adult male subjects (i.e., whole blood:plasma partitioning ratio).
Character the Clearance (CL) after IV dosing of NX-5948in healthy adults male subjects.
Character the Volume of distribution (Vz) after IV dosing of NX-5948in healthy adults male subjects.
Phase 1a
Phase 1a
Phase 1b Part 1
Phase 1a / Phase 1b Part 1
Phase 1b Part 2
| Arm | Type | Description |
|---|---|---|
| Arm A: NX-5948 | EXPERIMENTAL | - |
| Arm B: Pirtobrutinib | EXPERIMENTAL | - |
| NX-5948 | EXPERIMENTAL | - |
| NX-5948 + venetoclax | EXPERIMENTAL | - |
| NX-5948 + venetoclax + rituximab | EXPERIMENTAL | - |
| NX-5948 + venetoclax + obinutuzumab | EXPERIMENTAL | - |
| NX-5948 tablet and capsule under fasting and fed conditions; with and without placebo | EXPERIMENTAL | - |
| NX-5948 tablet and capsule with and without esomeprazole under fasting and fed conditions | EXPERIMENTAL | - |
| NX-5948 with and without famotidine under fasting and fed conditions | EXPERIMENTAL | - |
| Midazolam with and without NX-5948 | EXPERIMENTAL | - |
| Digoxin with and without NX-5948 | EXPERIMENTAL | - |
| Rosuvastatin with and without NX-5948 | EXPERIMENTAL | - |
| NX-5948 with and without quinidine | EXPERIMENTAL | - |
| Active Treatment Arm IV and Oral | EXPERIMENTAL | This single Arm will include a single dose by IV and a single dose given by mouth for all 8 subjects. |
| Phase 1a Dose Escalation | EXPERIMENTAL | Multiple dose levels of NX-5948 to be evaluated; determination of Maximum Tolerated Dose/Phase 1b recommended dose(s) |
| Phase 1b Part 1 Cohort 1 in CLL or SLL with prior BTKi and BCL2i | EXPERIMENTAL | 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. |
| Phase 1b Part 1 Cohort 2 in CLL/SLL with non-C481S BTK mutations | EXPERIMENTAL | 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 |
| Phase 1b Part 1 Cohort 3 in CLL/SLL with prior non-covalent BTKi | EXPERIMENTAL | CLL/SLL with prior exposure to ncBTKi and are BCL-2i naïve. |
| Phase 1b Part 1 Cohort 4 in CLL/SLL with TP53 or 17p deletion, 2L, prior BTKi | EXPERIMENTAL | Patients with documented TP53 mutation or 17p deletion and 1 prior line of therapy that included a BTKi and are BCL-2i naïve. |
| Phase 1b Part 1 Cohort 5 in CLL/SLL with 2L+, prior BTKi | EXPERIMENTAL | Patients with at least 1 prior line of therapy that included a BTKi and are BCL-2i naïve. |
| Phase 1b Part 1 Cohort 6 in MCL | EXPERIMENTAL | Non-blastoid MCL with prior exposure to a BTKi and an anti-CD20 monoclonal antibody (mAb)-based chemoimmunotherapy regimen |
| Phase 1b Part 1 Cohort 7 in MZL | EXPERIMENTAL | MZL (EMZL, MALT, NMZL, SMZL) with prior exposure to an anti-CD20 mAb-based chemo-immunotherapy regimen and an additional line of therapy |
| Phase 1b Part 1 Cohort 8 in WM (3L+) | EXPERIMENTAL | WM with prior exposure to a BTKi and at least an additional line of therapy |
| Phase 1b Part 1 Cohort 9 in WM (2L) | EXPERIMENTAL | WM following upfront therapy with a BTKi |
| Phase 1b Part 1 Cohort 10 in DLBCL | EXPERIMENTAL | 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 |
| Phase 1b Part 1 Cohort 11 in FL | EXPERIMENTAL | FL (grade 1-3a) with prior exposure to an anti-CD20 mAb-based chemoimmunotherapy regimen and an additional line of therapy |
| Phase 1b Part 1 Cohort 12 in PCNSL/SCNSL | EXPERIMENTAL | 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 |
| Phase 1b Part 1 Cohort 13 in PCNSL | EXPERIMENTAL | PCNSL following upfront therapy and with no prior exposure to a BTKi (2L). |
| Phase 1b Part 2 in CLL or SLL with prior BTKi and BCL-2i | EXPERIMENTAL | CLL or SLL with prior exposure to both a Bruton's tyrosine kinase inhibitor (BTKi) and BCL-2 inhibitor |
| Phase 1b Part 1 Cohort 14 in first-line WM | EXPERIMENTAL | Treatment-naïve WM deemed unfit for chemoimmunotherapy |
| Phase 1b Part 1 Cohort 15 in BTKi-naive CLL/SLL | EXPERIMENTAL | First-line (1L) or second-line+ (2L)+ CLL/SLL with no prior exposure to a BTKi |
| Phase 1b Part 1 Cohort 16 in CLL/SLL with secondary warm autoimmune hemolytic anemia (wAIHA) | EXPERIMENTAL | BTKi-exposed R/R CLL or SLL with secondary wAIHA |
| Phase 1b Part 1 Cohort 17 in CLL/SLL with CNS involvement | EXPERIMENTAL | BTKi-exposed R/R CLL or SLL with CNS involvement |
| Name | Type | Description |
|---|---|---|
| NX-5948 | DRUG | Administered orally once daily |
| Pirtobrutinib | DRUG | Administered orally once daily per prescribing information |
| venetoclax | DRUG | Administered orally once daily as a tablet per prescribing information |
| rituximab | DRUG | Administered as an intravenous (IV) infusion per prescribing information |
| obinutuzumab | DRUG | Administered as an IV infusion per prescribing information |
| Esomeprazole | DRUG | Administered orally in capsule form |
| Placebo | DRUG | Administered orally matching NX-5948 tablets |
| Famotidine | DRUG | Administered orally in tablet form |
| Midazolam | DRUG | Administered orally in syrup form |
| Digoxin | DRUG | Administered orally in tablet form |
| Rosuvastatin | DRUG | Administered orally in tablet form |
| Quinidine | DRUG | Administered orally in tablet form |
Key Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 * Adequate organ and bone marrow function * Confirmed diagnosis of CLL/SLL that meets iwCLL 2018 criteria for diagnosis and systemic treatment * Received at least 1 prior line of therapy for CLL/SLL tha...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Incyte Corporation | INCY | 2 | PHASE2 | Ruxolitinib, Pembrolizumab |
| Takeda Pharmaceutical Co. Ltd. Sponsored ADR | TAK | 1 | - | Undisclosed |
NX-5948 is an investigational small molecule being studied for the treatment of B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL). It is also being evaluated in healthy volunteers for pharmacokinetic studies. The drug is in clinical development and has not been approved by the FDA.
NX-5948 targets Bruton's tyrosine kinase (BTK), a protein involved in B-cell receptor signaling. By inhibiting BTK, the drug aims to disrupt the survival and proliferation of malignant B-cells. This mechanism is being investigated in clinical trials for B-cell lymphomas and chronic lymphocytic leukemia.
NX-5948 is being developed by Nurix Therapeutics, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol NRIX. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with B-cell malignancies and in healthy volunteers.
NX-5948 is in Phase 3 clinical development for relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma. It has received Fast Track designation from the FDA. The drug is investigational and not yet approved for any indication.
NX-5948 is being studied in several trials, including NCT07520006, a Phase 1 combination study in B-cell malignancies; NCT07516093, a Phase 3 trial versus pirtobrutinib in relapsed/refractory CLL/SLL; NCT07221500, a Phase 2 trial in CLL/SLL after prior BTK and BCL-2 inhibitor treatment; and NCT06717269, a completed Phase 1 study in healthy volunteers.
No, NX-5948 is not the same as pirtobrutinib. NX-5948 is an investigational BTK inhibitor developed by Nurix Therapeutics. Pirtobrutinib is a different BTK inhibitor. The two drugs are being compared directly in a Phase 3 clinical trial for relapsed or refractory CLL/SLL.