Sonrotoclax

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.

Defined as the proportion of participants who achieved a complete response (CR), complete remission with incomplete marrow recovery (CRi), nodular partial response (nPR), or partial response (PR) per the 2018 iwCLL guidelines for participants with chronic lymphocytic leukemia (CLL) or Defined as the proportion of participants who achieved PR or better per the Lugano Classification for partiticpants with small lymphocytic lymphoma (SLL)

Incidence of protocol-defined DLTs during the first treatment cycle.

Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Sonrotoclax

Proportion of participants achieving complete remission (CR), complete remission with limited count recovery (CRL), or complete remission with partial hematologic recovery (CRh).

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 included the following events without a clear alternative cause other than study drug: Hematologic Toxicity: * Grade ≥ 3 febrile neutropenia; * Grade ≥ 3 thrombocytopenia lasting \> 7 days or resulting in clinically significant bleeding; * Any Grade ≥ 4 hematological toxicities, except for Grade 4 neutropenia lasting ≤ 7 days with or without treatment, Grade 4 lymphopenia, or Grade 4 leukopenia. Nonhematologic Toxicity: • Any Grade ≥ 3 nonhematologic toxicity with the following exceptions: * Laboratory tumor lysis syndrome (TLS) defined by the Howard criteria that resolves (≤ Grade 1 or baseline) in ≤ 3 days; * Individual TLS-related laboratory adverse events that resolve (≤ Grade 1or baseline) in ≤ 3 days with or without treatment; * Grade 3 gastrointestinal toxicity that resolves to ≤ Grade 2 following therapeutic intervention in ≤ 7 days; * Asymptomatic biochemical laboratory abnormalities that resolve (≤ Grade 1 or baseline) in ≤ 7 days with or without supportive care.

An adverse event is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. A serious adverse event is any untoward medical occurrence that, at any dose: * Resulted in death * Was life-threatening * Required hospitalization or prolongation of existing hospitalization. * Resulted in disability/incapacity. * Was a congenital anomaly/birth defect. * Was considered a significant medical adverse event by the investigator or sponsor based on medical judgment.

Tumor lysis syndrome (TLS) occurs when large numbers of cancer cells die rapidly, releasing their contents (such as potassium, phosphorus, and nucleic acids) into the bloodstream faster than the kidneys can filter them out. This rapid breakdown causes a dangerous chain reaction of metabolic and electrolyte imbalances.

ORR is defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) per the Lugano Classification for non-Hodgin lymphoma.

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

The RP2D will be decided by the sponsor and based on the safety monitoring committee recommendation considering totality of data.

All AEs, including DLT events, will be assessed per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 (or the Grading Scale for Hematologic Toxicity in CLL Studies as appropriate).

CR plus CRh will be defined as the percentage of participants whose best overall response (BOR) is CR plus CRh. BOR will be defined as the best response recorded from the first dose of study drug until data cut or the initiation of new anticancer treatment.

The mOR will be defined as the percentage of participants whose BOR is achieving CR, marrow complete remission (mCR), or partial remission (PR) at any time point during the study for myelodysplastic/myeloproliferative neoplasm (MDS/MPN).