Study of Sonrotoclax (BGB-11417) Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma

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.

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

IRC review for response assessments was only performed for Part 1 participants assigned to the 320 mg dose level.

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

DOR is defined as the time from the date of the first documented response (PR or better) after treatment initiation until the date of first documented disease progression or death due to any cause; whichever occurred first, per the Lugano classification for non-Hodgkin lymphoma.

IRC review for response assessments was only performed for Part 1 participants assigned to the 320 mg dose level.

DOR was estimated using the Kaplan-Meier method.

DOR is defined as the time from the date of the first documented response (PR or better) after treatment initiation until the date of first documented disease progression or death due to any cause, whichever occurred first. DOR was estimated using the Kaplan-Meier method.

PFS is defined as the time from the date of the first study dose until the date of first documented disease progression or death due to any cause, whichever occurred first.

IRC review for response assessments was only performed for Part 1 participants assigned to the 320 mg dose level.

PFS was estimated using the Kaplan-Meier method.

PFS is defined as the time from the date of the first study dose until the date of first documented disease progression or death due to any cause, whichever occurred first. PFS was estimated using the Kaplan-Meier method.

Time to response is defined as the time from start of treatment to first documentation of response (PR or better). IRC review for response assessments was only performed for Part 1 participants assigned to the 320 mg dose level.

TTR is defined as the time from start of treatment to first documentation of response (PR or better).

Overall survival is defined as the time from the start of treatment to the date of death due to any cause. OS was estimated using the Kaplan-Meier method.

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.

Duration of response is defined as the time from the date of the first documented response (PR or better) after treatment initiation until the date of first documented disease progression or death due to any cause, whichever occurred first. DOR was estimated using the Kaplan-Meier method.

Duration of response is defined as the time from the date of the first documented response (PR or better) after treatment initiation until the date of first documented disease progression or death due to any cause, whichever occurred first. DOR was estimated using the Kaplan-Meier method.

PFS is defined as the time from the date of the first study dose until the date of first documented disease progression or death due to any cause, whichever occurred first. PFS was estimated using the Kaplan-Meier method.

PFS is defined as the time from the date of the first study dose until the date of first documented disease progression or death due to any cause, whichever occurred first. PFS was estimated using the Kaplan-Meier method.

Time to response is defined as the time from start of treatment to first documentation of response (PR or better).

Time to response is defined as the time from start of treatment to first documentation of response (PR or better).

Overall survival is defined as the time from the start of treatment to the date of death due to any cause. OS was estimated using the Kaplan-Meier method.

The NFlymSI-18 is a patient-reported outcome questionnaire that was developed to measure disease-specific symptoms and/or treatment-related concerns in patients with advanced lymphoma. The NFLymSI-18 questionnaire includes 18 separate questions about disease symptoms in the last 7 days; participants are asked to respond to each question on a scale from 0 (Not at all) to 4 (Very much). The 18 questions are grouped into 4 subscale scores: "Disease related symptoms - physical," "Disease related symptoms - emotional," "Treatment side effects," and "Function and wellbeing." The Disease Related Symptoms - Physical subscale score ranges from 0 to 36, where higher scores indicate better health-related quality of life (HRQoL).

The NFlymSI-18 is a patient-reported outcome questionnaire that was developed to measure disease-specific symptoms and/or treatment-related concerns in patients with advanced lymphoma. The NFLymSI-18 questionnaire includes 18 separate questions about disease symptoms in the last 7 days; participants are asked to respond to each question on a scale from 0 (Not at all) to 4 (Very much). The 18 questions are grouped into 4 subscale scores: "Disease related symptoms - physical," "Disease related symptoms - emotional," "Treatment side effects," and "Function and wellbeing." The Treatment Side-Effects subscale score ranges from 0 to 12, where higher scores indicate better health-related quality of life (HRQoL).

The EQ-5D VAS measures participants' self-rated health status on a scale from 0 to 100, with 100 = 'the best health you can imagine' and 0 = 'the worst health you can imagine'. Higher scores on VAS indicate higher health status.

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.