Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Sonrotoclax Tablet for Oral Suspension, Sonrotoclax for
Sonrotoclax · 12 trials · 24 indications
PFS is defined as the time from the date of randomization to the date of disease progression as determined by IRC or death due to any cause, whichever occurs first.
Rate of uMRD4 is defined as the percentage of participants that achieved uMRD4 measured in both peripheral blood (PB) and bone marrow aspirate (BMA) at the post-treatment follow-up visit (PTFU1) based on next generation sequencing (NGS).
PFS is defined as the time from randomization to the date of progression or death, whichever occurs first.
PFS is defined as the time from randomization to the date of progression or death, whichever occurs first.
PFS is defined as the time from the date of enrollment to the date of first confirmed disease progression or death due to any cause, whichever occurs first, as determined by independent review committee (IRC)
Undetectable measurable residual disease uMRD4 rate at the first Post- Treatment Follow-up (PTFU 1) Visit will be based on next-generation sequencing.
event free survival rate
Best CR/CRi rate per the Independent Review Committee (IRC) response assessment using the 2018 International Workshop on Chronic Lymphocytic Leukemia guidelines with modification for treatment-related lymphocytosis for participants with CLL
MRR is defined as the percentage of participants achieving partial response (PR) or better, as assessed by the Independent Review Committee (IRC) per the 11th International Workshop on Waldenström Macroglobulinemia (IWWM-11) WM response criteria.
Assessed by treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and laboratory abnormalities,. Includes adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria.
Dose selected based on safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity observed in Part 1, as determined by the Safety Monitoring Committee (SMC)
TLS will be defined by Howard criteria during the schedule-limiting toxicity (SLT) evaluation window
DLTs will be based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and will include most grade 3 or higher events, as defined in the protocol.
Defined as the percentage of participants who achieved a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per International Myeloma Working Group (IMWG) criteria
Defined as the percentage of participants with a documented VGPR or better (including sCR, CR, and VGPR)
defined as the percentage of participants with a documented CR or sCR
| Arm | Type | Description |
|---|---|---|
| Arm A: Sonrotoclax plus Zanubrutinib | EXPERIMENTAL | Participants will receive sonrotoclax and zanubrutinib for a fixed duration followed by observation. |
| Arm B: Venetoclax plus Acalabrutinib | ACTIVE_COMPARATOR | Participants will receive venetoclax and acalabrutinib for a fixed duration followed by observation. |
| Arm A: Sonrotoclax plus Obinutuzumab | EXPERIMENTAL | Sonrotoclax and obinutuzumab will be administered in combination. |
| Arm B: Sonrotoclax plus Rituximab | EXPERIMENTAL | Sonrotoclax and rituximab will be administered in combination. |
| Arm C: Sonrotoclax plus Obinutuzumab (MRD) | EXPERIMENTAL | Sonrotoclax and obinutuzumab will be administered in combination with treatment guided by evaluation of minimal residual disease (MRD). |
| Arm D: Venetoclax plus Rituximab | ACTIVE_COMPARATOR | Venetoclax and rituximab will be administered in combination. |
| Arm B: placebo plus zanubrutinib | PLACEBO_COMPARATOR | Placebo and zanubrutinib will be administered in combination. |
| Sonrotoclax Plus Zanubrutinib | EXPERIMENTAL | Participants will receive from start of Cycle 1 a standard dose of zanubrutinib once or twice daily orally and in combination with sonrotoclax starting from Cycle 4 onwards at increasing doses until target dose is reached and continuing until end of Cycle 15 (each cycle is 28 days) |
| Venetoclax Plus Obinutuzumab | ACTIVE_COMPARATOR | Participants will receive obinutuzumab 100mg intravenously on Day 1 Cycle 1, followed by 900 mg on Day 2 Cycle 1 (or alternatively receive 1000 mg intravenously on Day 1), followed by 1000 mg on Days 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2 through 6 (each cycle is 28 days) in combination with venetoclax at increasing doses until target dose is reached from Day 22 Cycle 1 until end of Cycle 12 (each cycles is 28 days) |
| Assigned Interventions | EXPERIMENTAL | Experimental: Sonrotoclax combined with intensive chemotherapy. Subjects receive induction therapy consisting of sonrotoclax combined with a 3+7 regimen. According to the ELN risks and MRD status, subjects who achieve composite complete remission (CRc) proceed with consolidation therapy, and allogeneic hematopoietic stem-cell transplant (allo-HSCT) can be included per investigator's decision. After the consolidation, subjects will receive sonrotoclax combined with azacitidine (AZA) alternating with AZA monotherapy every 2 cycles as maintenance therapy until intolerable toxicity, 12 months, relapse, death, withdrawal of informed consent, or study termination determined by investigators, whichever occurs first. |
| Arm A: Combination Therapy: Sonrotoclax + Zanubrutinib | EXPERIMENTAL | Participants will receive sonrotoclax in combination with zanubrutinib daily for a fixed duration of 15 cycles. |
| Arm B: Monotherapy: Zanubrutinib | ACTIVE_COMPARATOR | Participants will receive zanubrutinib monotherapy daily until disease progression or unacceptable toxicity, whichever occurs first. |
| Cohort 1 | EXPERIMENTAL | Participants with R/R disease to both Bruton tyrosine kinase (BTK) inhibitor and anti-CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor will receive sonrotoclax at a standard dose, given orally once daily. |
| Cohort 2 | EXPERIMENTAL | Participants with R/R disease to anti-CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor and were intolerant to BTK inhibitor will receive sonrotoclax at a standard dose, given orally once daily. |
| Cohort 3 | EXPERIMENTAL | Participants with R/R disease to a BTK inhibitor treatment and are unsuitable for chemoimmunotherapy will receive sonrotoclax at a standard dose, given orally once daily. |
| Cohort 4 | EXPERIMENTAL | Participants with previously untreated WM will receive sonrotoclax and zanubrutinib combination therapy for a fixed duration. |
| Cohort 1: Sonrotoclax + Azacitidine (R/R AML) | EXPERIMENTAL | Participants with relapsed or refractory acute myeloid leukemia (R/R AML) will receive sonrotoclax in combination with azacitidine. Treatment will be administered in a dose-escalation phase (Part 1) to determine the recommended dose for expansion (RDFE), followed by a dose-expansion phase (Part 2) at the RDFE to further evaluate safety, tolerability, pharmacokinetics, and preliminary antitumor activity. |
| Cohort 2: Sonrotoclax + Inotuzumab Ozogamicin + Dexamethasone (R/R B-cell ALL) | EXPERIMENTAL | Participants with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-cell ALL) receive sonrotoclax in combination with inotuzumab ozogamicin and dexamethasone. Treatment will be administered in a dose-escalation phase (Part 1) to determine the recommended dose for expansion (RDFE), followed by a dose-expansion phase (Part 2) at the RDFE to further evaluate safety, tolerability, pharmacokinetics, and preliminary antitumor activity. Enrollment may be paused based on futility criteria. |
| Arms: 1A,1B and 2A: Zanubrutinib + Sonrotoclax for TN CLL | EXPERIMENTAL | Participants will receive zanubrutinib alone, followed by a combination with sonrotoclax initiated with a ramp-up according to each schedule defined in the protocol. The total treatment duration is of 15 cycles of 28 days (including the phase of sonrotoclax dose ramp-up) |
| Arms: 1C and 2B: Zanubrutinib + Sonrotoclax for R/R MCL | EXPERIMENTAL | Participants will receive zanubrutinib alone, followed by a combination with sonrotoclax initiated with a ramp-up according to each schedule defined in the protocol, for a total of 27 cycles of 28 days (including the phase of sonrotoclax ramp-up), then will continue on zanubrutinib alone until progression of their disease or other treatment discontinuation criteria. |
| Part A: Phenytoin + Sonrotoclax | EXPERIMENTAL | Part A is designed to determine the effect of multiple doses of phenytoin on sonrotoclax in healthy participants. |
| Part B: Itraconazole + Sonrotoclax | EXPERIMENTAL | Part B is designed to determine the effect of multiple doses of itraconazole on sonrotoclax in healthy participants. |
| Part 1 Dose Escalation | EXPERIMENTAL | Dose-escalation and de-escalation to determine maximum tolerated dose (MTD) of sonrotoclax plus dexamethasone, sonrotoclax plus dexamethasone plus carfilzomib, sonrotoclax plus dexamethasone plus daratumumab, and sonrotoclax plus dexamethasone plus pomalidomide. |
| Part 2 Cohort Expansion | EXPERIMENTAL | There will be up to 7 expansion cohorts to further evaluate the safety and efficacy of sonrotoclax monotherapy, sonrotoclax plus dexamethasone in combination with dexamethasone plus carfilzomib, and in combination with dexamethasone plus daratumumab |
| Sonrotoclax Monotherapy Dose Finding: Part 1 | EXPERIMENTAL | Participants with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) or transformed NHL, mantle cell lymphoma (MCL); Waldenströms macroglobulinemia (WM); and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive oral sonrotoclax evaluated as monotherapy. |
| Sonrotoclax Monotherapy Expansion Cohorts: Part 2 | EXPERIMENTAL | Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral sonrotoclax at the RP2D dose to further define the safety profile. |
| Sonrotoclax + Zanubrutinib Combination Therapy Dose Finding: Part 3 | EXPERIMENTAL | Participants with R/R MCL, R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib. |
| Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 4 | EXPERIMENTAL | Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib at an RP2D dose to further define the safety profile. |
| Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5 | EXPERIMENTAL | Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib. |
| Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6 | EXPERIMENTAL | Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib at an RP2D dose to further define the safety profile. |
| Name | Type | Description |
|---|---|---|
| Sonrotoclax | DRUG | Administered orally. |
| Zanubrutinib | DRUG | Administered orally. |
| Acalabrutinib | DRUG | Administered orally. |
| Venetoclax | DRUG | Administered orally. |
| Obinutuzumab | DRUG | Administered intravenously |
| Rituximab | DRUG | Administered intravenously |
| Placebo | DRUG | Administered orally |
| idarubicin/daunorubicin | DRUG | idarubicin: On D1-3, intravenously, 10 mg/m\^2 for subjects aged \<60 years, 6 mg/m\^2 for subjects aged ≥60 years daunorubicin: On D1-3, intravenously, 60 mg/m\^2 for subjects aged \<60 years, 40 mg/m\^2 for subjects aged ≥60 years |
| Cytarabine | DRUG | In induction therapy phase: intravenously, 100 mg/m\^2 on D1-7. In consolidation therapy phase: subjects with favorable-risk and MRD negative will receive cytarabine intravenously at 2 g/m\^2/q12h for those aged \<60 years, at 1g/m\^2/q12h for those ≥60 years on D1-3 or 3+7 regimen, and subjects with favorable-risk and MRD positive or intermediate or adverse-risk will receive cytarabine intravenously at 1 g/m\^2/d q12h on D1-3(in combination with sonrotoclax). |
| Azacitidine | DRUG | 75 mg/m\^2, subcutaneously, once daily, on D1-7 |
| allo-HSCT | PROCEDURE | Per standard of procedure |
| Inotuzumab ozogamicin | DRUG | administered via intravenous infusion |
| Dexamethasone | DRUG | administered via intravenous injection or orally |
| Phenytoin | DRUG | Administered orally. |
| Itraconazole | DRUG | Administered orally. |
| Carfilzomib | DRUG | Administered intravenously weekly |
| Daratumumab | DRUG | Administered subcutaneously weekly |
| Pomalidomide | DRUG | Administered orally daily |
Inclusion Criteria: * Treatment-naïve (TN) adults with confirmed diagnosis of CLL which requires treatment * Eastern Cooperative Oncology Group (ECOG) score 0, 1, or 2 * Measurable disease by Computer Tomography/Magnetic Resonance Imaging * Adequate bone marrow and organ function Exclusion Criteri...
Sonrotoclax is an investigational small molecule being studied in oncology. Clinical trials are evaluating it in relapsed/refractory multiple myeloma, chronic lymphocytic leukemia (CLL), acute myeloid leukemia, and Waldenstrom macroglobulinemia. It is also being studied in healthy volunteers for drug interaction effects. Sonrotoclax is not approved and remains in clinical development.
Sonrotoclax is a small molecule oncology drug, but its specific molecular target is not disclosed in the available information. It is being studied across multiple hematologic malignancies, including multiple myeloma, CLL, and acute myeloid leukemia, as monotherapy and in combination with other agents.
Sonrotoclax is being developed by BeOne Medicines Ltd., a company listed under the ticker ONC. The company is conducting multiple clinical trials of Sonrotoclax across various oncology indications, including a Phase 3 study in chronic lymphocytic leukemia.
Sonrotoclax is in Phase 3 clinical development. The most advanced study is a Phase 3 trial in chronic lymphocytic leukemia comparing Sonrotoclax plus zanubrutinib against venetoclax plus obinutuzumab. Additional Phase 1 and Phase 2 trials are also active in other indications.
Sonrotoclax has four clinical trials. NCT06073821 is a Phase 3 study in CLL. NCT04973605 is a Phase 1b/2 study in relapsed/refractory multiple myeloma. NCT06497062 is a Phase 2 study in acute myeloid leukemia. NCT06543043 is a completed Phase 1 healthy volunteer drug interaction study.
Sonrotoclax is also known as BGB-11417 in clinical trial documentation. Multiple trials reference Sonrotoclax (BGB-11417) in their titles, confirming these names refer to the same investigational drug. The drug is also referred to as Sonrotoclax Tablet for Oral Suspension.