Study of LOXO-305 (Pirtobrutinib) Versus Investigator's C... | NCT04666038

ID	Type	Description	Link
J2N-OX-JZNN	Other Identifier	Eli Lilly and Company
LOXO-BTK-20020	Other Identifier	Eli Lilly and Company

Name	Class
Eli Lilly and Company	INDUSTRY

Label	Type	Description	Intervention Names
Arm A - Pirtobrutinib	Experimental	Participants received 200 milligrams (mg) of pirtobrutinib administered orally once daily (QD) on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.	Drug: Pirtobrutinib
Arm B - Idelalisib plus Rituximab or Bendamustine plus Rituximab	Active Comparator	Participants received either 150 mg of idelalisib administered twice-daily (BID) orally on Days 1 through 28 of a 28-day cycle in combination with 375 milligram per square meter (mg/m^2) of rituximab by intravenous (IV) infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m^2 every 2 weeks (Q2W) and 3 IV infusions of rituximab 500 mg/m^2 every 4 weeks (Q4W) or 70 mg/m^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.	Drug: Idelalisib Drug: Bendamustine Drug: Rituximab

Name	Type	Description	Arm Group Labels	Other Names
Pirtobrutinib	Drug	Oral Pirtobrutinib	Arm A - Pirtobrutinib	LOXO-305

Measure	Description	Time Frame
Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC)	PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause, as evaluated by an IRC according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018.	Randomization to Disease Progression or Death Due to Any Cause (Up to 29 Months)

Measure	Description	Time Frame
PFS Assessed by Investigator	PFS is defined as time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an investigator according to iwCLL 2018.	Randomization to Disease Progression or Death Due to Any Cause (Up to 36 Months)
Overall Survival (OS)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Confirmed diagnosis of CLL/SLL requiring therapy as defined by iwCLL 2018 criteria.
Previously treated with a covalent BTK inhibitor.
Eastern Cooperative Oncology Group (ECOG) 0-2.
Absolute neutrophil count ≥ 0.75 × 10^9/L without granulocyte-colony-stimulating factor support, or ≥ 0.50 × 10^9/L in patients with documented bone marrow involvement considered to impair hematopoiesis. Granulocyte-colony-stimulating factor support is permitted in patients with documented bone marrow involvement.
Hemoglobin ≥ 8 g/dL or ≥ 6 g/dL in patients with documented bone marrow involvement considered to impair hematopoiesis. Transfusion support is permitted in patients with bone marrow involvement.
Platelets ≥ 50 × 10^9/L. If an investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ 75 × 10^9/L. Patients may enroll below these thresholds if the Investigator determines the cytopenia is related to bone marrow involvement considered to impair hematopoiesis. Patients with a platelet count < 30 x 10^9/L are excluded.
AST and ALT ≤ 3.0 x upper limit of normal (ULN).
Total bilirubin ≤ 1.5 x ULN.
Estimated creatinine clearance of ≥ 30 mL/min.

Exclusion Criteria:

Known or suspected Richter's transformation at any time preceding enrollment.
Known or suspected history of central nervous system (CNS) involvement by CLL/SLL.
Ongoing drug-induced liver injury.
Active uncontrolled auto-immune cytopenia.
Significant cardiovascular disease.
History of allogeneic or stem cell transplantation (SCT) or chimeric antigen receptor-modified T cells (CAR-T) therapy within the past 60 days.
Active hepatitis B or hepatitis C.
Known active cytomegalovirus (CMV) infection.
Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.
Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count.
Clinically significant active malabsorption syndrome or inflammatory bowel disease
Prior exposure to non-covalent (reversible) BTK inhibitor.
Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.
Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers.
Vaccination with a live vaccine within 28 days prior to randomization.
Patients with the following hypersensitivity:
1. Known hypersensitivity, including anaphylaxis, to any component or excipient of LOXO-305. For patients planned to receive idelalisib, known hypersensitivity, including anaphylaxis, to any component or excipient of idelalisib. For patients planned to receive bendamustine, known hypersensitivity, including anaphylaxis, to any component or excipient of bendamustine.
2. Prior significant hypersensitivity to rituximab.

Name	Affiliation	Role
Marisa Hill, MD	Loxo Oncology, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Southern Cancer Center, P.C.		Daphne	Alabama	36526	United States
Mitchell Cancer Institute -University of South Alabama

PubMed Identifier	Type	Citation	Retractions
42329537	Derived	Loubert A, Creel K, Bhandari NR, Hess LM, Ruppert AS, Abada P, Regnault A, Payakachat N. Psychometric analysis of new lymphoma-specific patient-reported symptom measures derived from the EORTC item library. J Patient Rep Outcomes. 2026 Jun 22. doi: 10.1186/s41687-026-01126-w. Online ahead of print.
40479620	Derived

ID	Title	Description
FG000	Arm A - Pirtobrutinib	Participants received 200 milligrams (mg) of pirtobrutinib administered orally once daily (QD) on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.
FG001	Arm B - Idelalisib Plus Rituximab or Bendamustine Plus Rituximab

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 14, 2024	Nov 13, 2024

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression-free Survival (PFS) Assessed by Independent Review Committee (IRC)

PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause, as evaluated by an IRC according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018.

All randomized participants, even if a participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received.

Posted

Median

95% Confidence Interval

Months

Randomization to Disease Progression or Death Due to Any Cause (Up to 29 Months)

ID	Title	Description
OG000	Arm A - Pirtobrutinib	Participants received 200 mg of pirtobrutinib administered orally QD on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.
OG001	Arm B - Idelalisib Plus Rituximab or Bendamustine Plus Rituximab	Participants received either 150 mg of idelalisib administered BID orally on Days 1 through 28 of a 28-day cycle in combination with 375 mg/m^2 of rituximab by IV infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m^2 Q2W and 3 IV infusions of rituximab 500 mg/m^2 Q4W or 70 mg/m^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.

Units	Counts
Participants	OG000119 OG001119

Title

Denominators

Categories

Title	Measurements
	OG00013.96(11.24 to 16.56) OG0018.74(8.08 to 10.38)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.0002	The 2-sided nominal p-value was calculated based on a stratified log-rank test.	Hazard Ratio (HR)	0.536			2-Sided	95	0.385	0.746			The Hazard Ratio (HR) & 95% confidence interval (CI) were estimated from a stratified Cox proportional hazards model.		Superiority

Secondary

PFS Assessed by Investigator

PFS is defined as time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an investigator according to iwCLL 2018.

Posted

Median

95% Confidence Interval

Months

Randomization to Disease Progression or Death Due to Any Cause (Up to 36 Months)

ID	Title	Description
OG000	Arm A - Pirtobrutinib	Participants received 200 mg of pirtobrutinib administered orally QD on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.
OG001	Arm B - Idelalisib Plus Rituximab or Bendamustine Plus Rituximab	Participants received either 150 mg of idelalisib administered BID orally on Days 1 through 28 of a 28-day cycle in combination with 375 mg/m^2 of rituximab by IV infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m^2 Q2W and 3 IV infusions of rituximab 500 mg/m^2 Q4W or 70 mg/m^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.

Secondary

Overall Survival (OS)

OS was defined as time from randomization to death due to any cause.

Posted

Median

95% Confidence Interval

Months

Randomization to Death from Any Cause (Up to 36 months)

ID	Title	Description
OG000	Arm A - Pirtobrutinib	Participants received 200 milligrams (mg) of pirtobrutinib administered orally once daily (QD) on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.
OG001	Arm B - Idelalisib Plus Rituximab or Bendamustine Plus Rituximab	Participants received either 150 mg of idelalisib administered BID orally on Days 1 through 28 of a 28-day cycle in combination with 375 mg/m^2 of rituximab by IV infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m^2 Q2W and 3 IV infusions of rituximab 500 mg/m^2 Q4W or 70 mg/m^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.

Secondary

Time to Next Treatment (TTNT)

TTNT was defined as time from the date of randomization to the date of initiation of the subsequent anticancer therapy for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), therapy of pirtobrutinib for Arm B patients, or death due to any cause, whichever occurs first.

Posted

Median

95% Confidence Interval

Months

Randomization to Subsequent Anticancer Therapy, Therapy of Pirtobrutinib or Death Due to Any Cause (Up to 36 Months)

ID	Title	Description
OG000	Arm A - Pirtobrutinib	Participants received 200 mg of pirtobrutinib administered orally QD on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.
OG001	Arm B - Idelalisib Plus Rituximab or Bendamustine Plus Rituximab	Participants received either 150 mg of idelalisib administered BID orally on Days 1 through 28 of a 28-day cycle in combination with 375 mg/m^2 of rituximab by IV infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m^2 Q2W and 3 IV infusions of rituximab 500 mg/m^2 Q4W or 70 mg/m^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.

Secondary

Event Free Survival (EFS)

EFS is defined as the time from randomization to the first occurrence of:

Documented disease progression per iwCLL 2018 criteria as assessed by Investigator; or
Initiation of subsequent anticancer therapy for CLL/SLL; or
Unacceptable toxicity leading to treatment discontinuation as assessed by the Investigator; or
Death (due to any cause).

Posted

Median

95% Confidence Interval

Months

Randomization to Disease Progression, Subsequent Anticancer Therapy, Unacceptable Toxicity Leading to Treatment Discontinuation, or Death Due to Any Cause (Up to 36 Months)

ID	Title	Description
OG000	Arm A - Pirtobrutinib	Participants received 200 mg of pirtobrutinib administered orally QD on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.
OG001	Arm B - Idelalisib Plus Rituximab or Bendamustine Plus Rituximab	Participants received either 150 mg of idelalisib administered BID orally on Days 1 through 28 of a 28-day cycle in combination with 375 mg/m^2 of rituximab by IV infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m^2 Q2W and 3 IV infusions of rituximab 500 mg/m^2 Q4W or 70 mg/m^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.

Secondary

Percentage of Participants With Overall Response Rate (ORR) Assessed by Investigator

ORR according to investigator-assessed best overall response (BOR) based on iwCLL 2018 is defined as the number of participants who achieve a BOR of complete response (CR), complete response with incomplete bone marrow recovery (CRi), nodular partial response (nPR) or partial response (PR) at or before the initiation of subsequent anticancer therapy divided by the total number of participants randomized to each treatment arm.

Posted

Number

95% Confidence Interval

percentage of participants

Randomization to Subsequent Anticancer Therapy, Disease Progression or Death Due to Any Cause (Up to 36 Months)

ID	Title	Description
OG000	Arm A - Pirtobrutinib	Participants received 200 mg of pirtobrutinib administered orally QD on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.
OG001	Arm B - Idelalisib Plus Rituximab or Bendamustine Plus Rituximab	Participants received either 150 mg of idelalisib administered BID orally on Days 1 through 28 of a 28-day cycle in combination with 375 mg/m^2 of rituximab by IV infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m^2 Q2W and 3 IV infusions of rituximab 500 mg/m^2 Q4W or 70 mg/m^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.

Secondary

Time to Worsening (TTW) of CLL/SLL Related Symptoms

TTW was defined as a change in score greater than the meaningful within-person change for worsening in score. Scores were furthermore required to be sustained. To meet the requirement for sustained change, the assessment following the first observation of a meaningful worsening of the score (event date) was also required to show a meaningful worsening compared to baseline. The event date was defined as the first of these consecutive events. The European Organization for Research and Treatment of Cancer Item Library 87 was used, which is scored from 0-100, with higher scores reflecting more symptoms.

The time to sustained patient-reported outcome (PRO) deterioration was calculated using all on-treatment assessment time points up to the Week 25 (Arm A & Arm B - Idelalisib plus Rituximab) and up to Week 21 + Safety follow-up of up to 5 weeks (Arm B - Bendamustine plus Rituximab) assessment time point prior to disease progression.

Posted

Median

95% Confidence Interval

Months

Baseline up to Week 25 (Arm A and Arm B - Idelalisib plus Rituximab) & Baseline up to Week 21 + Safety Follow-Up of up to 5 Weeks (Arm B - Bendamustine plus Rituximab)

ID	Title	Description
OG000	Arm A - Pirtobrutinib	Participants received 200 mg of pirtobrutinib administered orally QD on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.

Secondary

Time to Worsening (TTW) of Physical Function

Time of worsening was defined as a change in score greater than the meaningful within-person change for worsening in score. Scores were furthermore required to be sustained. To meet the requirement for sustained change, the assessment following the first observation of a meaningful worsening of the score (event date) was also required to show a meaningful worsening compared to baseline. The event date was defined as the first of these consecutive events. The European Organization for Research and Treatment of Cancer Item Library 87 was used, which is scored from 0-100, with higher scores reflecting more symptoms.

The time to sustained PRO deterioration was calculated using all on-treatment assessment time points up to the Week 25 (Arm A and IdelaR) and up to Week 21 + Safety follow-up (BR) assessment time point prior to disease progression.

Posted

Median

95% Confidence Interval

Months

Baseline up to Week 25 (Arm A and Arm B - Idelalisib plus Rituximab) & Baseline up to Week 21 + Safety Follow-Up of up to 5 Weeks (Arm B - Bendamustine plus Rituximab)

ID	Title	Description
OG000	Arm A - Pirtobrutinib	Participants received 200 mg of pirtobrutinib administered orally QD on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0006 events3 affected116 at risk EG0013 events2 affected109 at risk
Bone marrow necrosis	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0014 events4 affected109 at risk
Haemolysis	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0012 events2 affected109 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected116 at risk EG0013 events3 affected109 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Cardiac arrest	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0011 events1 affected109 at risk
Cardiac failure	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected116 at risk EG0010 events0 affected109 at risk
Coronary artery disease	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Eye haemorrhage	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Colitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0014 events4 affected109 at risk
Diverticulum intestinal	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Intussusception	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0012 events2 affected109 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0011 events1 affected109 at risk
General physical health deterioration	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0012 events2 affected109 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Nodule	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected116 at risk EG0015 events4 affected109 at risk
Acute hepatic failure	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Hypogammaglobulinaemia	Immune system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0012 events1 affected109 at risk
Immune system disorder	Immune system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Bronchitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0011 events1 affected109 at risk
Campylobacter infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Cellulitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0011 events1 affected109 at risk
Covid-19	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected116 at risk EG0016 events6 affected109 at risk
Covid-19 pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0007 events5 affected116 at risk EG0014 events4 affected109 at risk
Device related infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Diverticulitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Escherichia sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0011 events1 affected109 at risk
Infectious pleural effusion	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Infective exacerbation of bronchiectasis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Influenza	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0011 events1 affected109 at risk
Klebsiella urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected116 at risk EG0010 events0 affected109 at risk
Lower respiratory tract infection viral	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Neutropenic sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Oesophageal candidiasis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Oropharyngeal candidiasis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Osteomyelitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Pharyngitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00029 events20 affected116 at risk EG00115 events12 affected109 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Pneumonia cytomegaloviral	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Pneumonia haemophilus	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Pneumonia influenzal	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected116 at risk EG0010 events0 affected109 at risk
Pneumonia klebsiella	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Pneumonia viral	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected116 at risk EG0011 events1 affected109 at risk
Pulmonary sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0011 events1 affected109 at risk
Sinusitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0012 events2 affected109 at risk
Viral infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Vulval abscess	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected32 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0013 events3 affected109 at risk
Injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Pneumothorax traumatic	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Blood creatinine increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0011 events1 affected109 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0003 events2 affected116 at risk EG0010 events0 affected109 at risk
Tumour compression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0012 events1 affected109 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Cerebral infarction	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected116 at risk EG0010 events0 affected109 at risk
Dysarthria	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Headache	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Spinal cord compression	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Syncope	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Bipolar disorder	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Delirium	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Depression	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0011 events1 affected109 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Renal disorder	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Renal failure	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Renal impairment	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected34 at risk EG0010 events0 affected109 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Pharyngeal mass	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0011 events1 affected109 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0012 events2 affected109 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Purpura	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Aortic dilatation	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Circulatory collapse	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0010 events0 affected109 at risk
Haematoma	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG0011 events1 affected109 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG00029 events21 affected116 at risk EG00128 events21 affected109 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG00044 events21 affected116 at risk EG00126 events17 affected109 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG00013 events8 affected116 at risk EG0019 events7 affected109 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected116 at risk EG00110 events8 affected109 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected116 at risk EG0019 events8 affected109 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0009 events8 affected116 at risk EG00118 events15 affected109 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00025 events20 affected116 at risk EG00145 events30 affected109 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00015 events13 affected116 at risk EG00137 events23 affected109 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events2 affected116 at risk EG00111 events8 affected109 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00010 events7 affected116 at risk EG00126 events18 affected109 at risk
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG00012 events10 affected116 at risk EG00110 events6 affected109 at risk
Chills	General disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected116 at risk EG0019 events9 affected109 at risk
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG00019 events16 affected116 at risk EG00129 events27 affected109 at risk
Oedema peripheral	General disorders	MedDRA 27.0	Systematic Assessment	EG00015 events13 affected116 at risk EG0018 events7 affected109 at risk
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG00021 events14 affected116 at risk EG00135 events28 affected109 at risk
Bronchitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected116 at risk EG00111 events8 affected109 at risk
Covid-19	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00017 events14 affected116 at risk EG00121 events18 affected109 at risk
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00017 events15 affected116 at risk EG0016 events4 affected109 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00018 events11 affected116 at risk EG0018 events7 affected109 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00013 events8 affected116 at risk EG0014 events4 affected109 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected116 at risk EG00121 events16 affected109 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0005 events4 affected116 at risk EG00129 events18 affected109 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0007 events6 affected116 at risk EG00123 events13 affected109 at risk
Blood creatinine increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0008 events7 affected116 at risk EG0018 events8 affected109 at risk
Neutrophil count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG00018 events9 affected116 at risk EG00141 events19 affected109 at risk
Platelet count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0006 events2 affected116 at risk EG00124 events13 affected109 at risk
Weight decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0005 events4 affected116 at risk EG00119 events18 affected109 at risk
White blood cell count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected116 at risk EG00134 events10 affected109 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0005 events5 affected116 at risk EG00115 events15 affected109 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00010 events7 affected116 at risk EG0016 events4 affected109 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00010 events6 affected116 at risk EG0015 events5 affected109 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0007 events6 affected116 at risk EG00111 events8 affected109 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00013 events9 affected116 at risk EG00111 events10 affected109 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00012 events10 affected116 at risk EG0018 events5 affected109 at risk
Dizziness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected116 at risk EG0019 events9 affected109 at risk
Headache	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG00014 events13 affected116 at risk EG00118 events15 affected109 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00022 events20 affected116 at risk EG00124 events20 affected109 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0006 events6 affected116 at risk EG00112 events8 affected109 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0009 events7 affected116 at risk EG0011 events1 affected109 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00012 events11 affected116 at risk EG00111 events9 affected109 at risk
Hypertension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0009 events9 affected116 at risk EG0015 events5 affected109 at risk

ID	Term
D015451	Leukemia, Lymphocytic, Chronic, B-Cell
D006402	Hematologic Diseases
D008228	Lymphoma, Non-Hodgkin
D016393	Lymphoma, B-Cell
D008223	Lymphoma

ID	Term
D015448	Leukemia, B-Cell
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D001562	Benzimidazoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	Arm A - Pirtobrutinib	Participants received 200 mg of pirtobrutinib administered orally QD on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.
BG001	Arm B - Idelalisib Plus Rituximab or Bendamustine Plus Rituximab	Participants received either 150 mg of idelalisib administered BID orally on Days 1 through 28 of a 28-day cycle in combination with 375 mg/m^2 of rituximab by IV infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m^2 Q2W and 3 IV infusions of rituximab 500 mg/m^2 Q4W or 70 mg/m^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A - Pirtobrutinib	Participants received 200 mg of pirtobrutinib administered orally QD on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.	38	119	60	116	94	116
EG001	Arm B - Idelalisib Plus Rituximab or Bendamustine Plus Rituximab	Participants received either 150 mg of idelalisib administered BID orally on Days 1 through 28 of a 28-day cycle in combination with 375 mg/m^2 of rituximab by IV infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m^2 Q2W and 3 IV infusions of rituximab 500 mg/m^2 Q4W or 70 mg/m^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.	32	119	53	109	103	109

ID	Term
C000723100	pirtobrutinib
C552946	idelalisib
D000069461	Bendamustine Hydrochloride
D000069283	Rituximab