Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
NX-5948 · 6 trials · 13 indications
Time from randomization to disease progression or death due to any cause, whichever is earlier
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.
Relative bioavailability of NX-5948 tablet, compared to capsule, will be measured using PK parameters (AUC)
Relative bioavailability of NX-5948 tablet, compared to capsule, will be measured using PK parameters (Tmax)
Evaluate the effect of food and the effect of multiple doses of esomeprazole on the single-dose PK of NX-5948 tablet
Evaluate the effect of food and the effect of multiple doses of esomeprazole on the single-dose PK of NX-5948 tablet
Evaluate the effect of food and the effect of multiple doses of esomeprazole on the single-dose PK of NX-5948 tablet
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 fasted and fed conditions | EXPERIMENTAL | - |
| NX-5948 tablet and capsule combined with esomeprazole under fasted conditions | 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 |
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 one prior line of therapy for CLL/SLL t...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Incyte Corporation | INCY | 2 | PHASE2 | Ruxolitinib, Pembrolizumab |
| Takeda Pharmaceutical Co. Ltd. Sponsored ADR | TAK | 1 | - | Undisclosed |