Trial Outcomes & Findings for ACP-196 Alone and in Combination With Pembrolizumab in Subjects With Advanced or Metastatic Pancreatic Cancer (NCT NCT02362048)

NCT ID: NCT02362048

Last Updated: 2019-10-01

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

77 participants

Primary outcome timeframe

Every 12 weeks for up to 2 years.

Results posted on

2019-10-01

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1 - Acalabrutinib Monotherapy Acalabrutinib 100 mg administered orally (PO) twice daily (BID)	Arm 2- Acalabrutinib+Pembrolizumab Acalabrutinib 100 mg PO BID plus pembrolizumab 200 mg administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Overall Study STARTED	37	40
Overall Study Enrolled	37	40
Overall Study Received Study Medication	35	38
Overall Study Discontinued Study	37	40
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	37	40

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

ACP-196 Alone and in Combination With Pembrolizumab in Subjects With Advanced or Metastatic Pancreatic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Monotherapy Arm n=35 Participants ACP-196 alone ACP-196	Combination Arm n=38 Participants ACP-196 in combination with pembrolizumab ACP-196 in combination with pembrolizumab	Total n=73 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	23 Participants n=7 Participants	43 Participants n=5 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Age, Continuous	62.9 Year STANDARD_DEVIATION 8.19 • n=5 Participants	61.3 Year STANDARD_DEVIATION 10.94 • n=7 Participants	62.1 Year STANDARD_DEVIATION 9.69 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	19 Participants n=7 Participants	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=5 Participants	33 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants	33 Participants n=7 Participants	62 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants	38 participants n=7 Participants	73 participants n=5 Participants

PRIMARY outcome

Timeframe: Every 12 weeks for up to 2 years.

Population: All participants with Baseline and at least one post-baseline target lesion measurement.

Outcome measures

Outcome measures
Measure	Arm 1 - Acalabrutinib Monotherapy n=29 Participants Acalabrutinib 100 mg administered orally (PO) twice daily (BID)	Arm 2- Acalabrutinib+Pembrolizumab n=27 Participants Acalabrutinib 100 mg PO BID plus pembrolizumab 200 mg administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Number of Participants With Overall Response Advanced or Metastatic Pancreatic Cancer.	0 Participants	3 Participants

Adverse Events

Arm 1 - Acalabrutinib Monotherapy

Serious events: 14 serious events

Other events: 34 other events

Deaths: 30 deaths

Arm 2- Acalabrutinib+Pembrolizumab

Serious events: 26 serious events

Other events: 38 other events

Deaths: 34 deaths

Serious adverse events

Other adverse events

Additional Information

Priti Patel, MD, Executive Director - Head of Clinical Development

Acerta Pharma, LLC

Phone: 1-888-292-9613

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Arm 1 - Acalabrutinib Monotherapy n=35 participants at risk Acalabrutinib 100 mg administered orally (PO) twice daily (BID)	Arm 2- Acalabrutinib+Pembrolizumab n=38 participants at risk Acalabrutinib 100 mg PO BID plus pembrolizumab 200 mg administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Blood and lymphatic system disorders Anaemia	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Cardiac disorders Atrial Fibrillation	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	5.3% 2/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Abdominal Pain	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	13.2% 5/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Nausea	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Vomiting	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	5.3% 2/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Abdomincal Distension	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Ascites	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Duodenal Ulcer	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Upper Gastrointestinal Haemorrage	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Pyrexia	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Asthenia	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Chills	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Hepatobiliary disorders Cholangitis	5.7% 2/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	5.3% 2/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Hepatobiliary disorders Autoimmune Hepatitis	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Hepatobiliary disorders Bile Duct Obstruction	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Hepatobiliary disorders Cholecystitis	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Hepatobiliary disorders Hepatic Function Abnormal	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Hepatobiliary disorders Portal Vien Thrombosis	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Pneumonia	5.7% 2/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Sepsis	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Abdominal Infection	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Bacteraemia	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Clostridium Difficile Colitis	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Escherichia Sepsis	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Escherichia Urinary Tract Infection	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Hepatic Infection	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Klebsiella Sepsis	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Septic Shock	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Injury, poisoning and procedural complications Hip Fracture	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Injury, poisoning and procedural complications Subdural Haemorrhage	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Investigations Blood Bilirubin Increased	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Investigations Troponin T Increased	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Dehydration	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Hypovolaemia	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Failure to Thrive	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Musculoskeletal and connective tissue disorders Back Pain	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Ascites	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour Associated Fever	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Nervous system disorders Somnolence	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.

Other adverse events
Measure	Arm 1 - Acalabrutinib Monotherapy n=35 participants at risk Acalabrutinib 100 mg administered orally (PO) twice daily (BID)	Arm 2- Acalabrutinib+Pembrolizumab n=38 participants at risk Acalabrutinib 100 mg PO BID plus pembrolizumab 200 mg administered as an intravenous (IV) infusion every 3 weeks (Q3W)
General disorders Chills	5.7% 2/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	10.5% 4/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Pyrexia	14.3% 5/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	23.7% 9/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Blood and lymphatic system disorders Anaemia	34.3% 12/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	36.8% 14/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Blood and lymphatic system disorders Thrombocytopenia	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	10.5% 4/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Cardiac disorders Sinus Tachycardia	5.7% 2/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Abdominal Pain	28.6% 10/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	55.3% 21/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Nausea	22.9% 8/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	36.8% 14/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Constipation	22.9% 8/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	34.2% 13/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Vomiting	17.1% 6/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	39.5% 15/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Gastrointestinal disorders Abdominal Distension	14.3% 5/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	23.7% 9/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Fatigue	31.4% 11/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	42.1% 16/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Oedema Peripheral	25.7% 9/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	13.2% 5/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Asthena	8.6% 3/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	5.3% 2/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Pain	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	5.3% 2/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Influenza like Illness	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	5.3% 2/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Chest Discomfort	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	5.3% 2/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Chest Pain	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	5.3% 2/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
General disorders Mucosal Inflammation	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	5.3% 2/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Urinary Tract Infection	5.7% 2/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	13.2% 5/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Pneumonia	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	7.9% 3/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Infections and infestations Upper Respiratory Tract Infection	5.7% 2/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Injury, poisoning and procedural complications Contusion	5.7% 2/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	5.3% 2/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Injury, poisoning and procedural complications Fall	5.7% 2/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	5.3% 2/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Investigations Blood Alkaline Phosphatase Increased	5.7% 2/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	15.8% 6/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Investigations Blood Creatinine Increased	14.3% 5/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	10.5% 4/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Investigations Alanine Aminotransferase Increased	8.6% 3/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	13.2% 5/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Investigations Blood Bilirubin Increased	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	10.5% 4/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Investigations Aspartate Aminotransferase Increased	5.7% 2/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	10.5% 4/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Investigations Platelet Count Decreased	14.3% 5/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	2.6% 1/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Investigations Lymphocyte Count Decreased	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	7.9% 3/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Decreased Appetite	31.4% 11/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	47.4% 18/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Dehydration	17.1% 6/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	18.4% 7/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Hyponatraemia	8.6% 3/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	23.7% 9/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Hypoalbuminaemia	8.6% 3/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	15.8% 6/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Hypokalaemia	8.6% 3/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	15.8% 6/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Hyperkalaemia	2.9% 1/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	7.9% 3/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	10.5% 4/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Musculoskeletal and connective tissue disorders Back Pain	22.9% 8/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	15.8% 6/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Musculoskeletal and connective tissue disorders Myalgia	14.3% 5/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	10.5% 4/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.
Musculoskeletal and connective tissue disorders Pain in Extremity	11.4% 4/35 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.	0.00% 0/38 • AE collected time frame was From the date of the first dose of study drug, through the treatment phase, and within 30 days following the last dose of Acalabrutinib or within 90 days following the last dose of Pembrolizumab. Subjects with multiple events for a given preferred term (PT) were counted only once for each PT. If the same event term was reported more than once for a subject, only the event with the highest grade was included.