Trial Outcomes & Findings for Study of the Combination of ACP-196 and Pembrolizumab in Subjects With Platinum Resistant Urothelial Bladder Cancer (NCT NCT02351739)

Last Updated: 2019-09-10

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

78 participants

Primary outcome timeframe

Every 12 weeks for up to 2 years.

Results posted on

2019-09-10

Participant Flow

Participant milestones

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

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of the Combination of ACP-196 and Pembrolizumab in Subjects With Platinum Resistant Urothelial Bladder Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab n=35 Participants Arm 1: pembrolizumab monotherapy pembrolizumab	ACP-196 in Combination With Pembrolizumab n=40 Participants Arm 2: ACP-196 in combination with pembrolizumab ACP-196 in combination with pembrolizumab	Total n=75 Participants Total of all reporting groups
Age, Continuous	65.8 Years STANDARD_DEVIATION 11.08 • n=5 Participants	66.4 Years STANDARD_DEVIATION 8.53 • n=7 Participants	66.1 Years STANDARD_DEVIATION 9.74 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	29 Participants n=7 Participants	57 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=5 Participants	40 Participants n=7 Participants	74 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	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	32 Participants n=5 Participants	37 Participants n=7 Participants	69 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Every 12 weeks for up to 2 years.

Population: The study participants had to have a minimum of one scan (for tumor assessment) after randomization/treatment in order to be considered analyzed. And some of the participants didn't make it to Wk 7 of treatment, hence reduction in the number of subjects analyzed.

Outcome measures

Outcome measures
Measure	Pembrolizumab n=31 Participants Arm 1: pembrolizumab monotherapy pembrolizumab	ACP-196 in Combination With Pembrolizumab n=34 Participants Arm 2: ACP-196 in combination with pembrolizumab ACP-196 in combination with pembrolizumab
Number of Participants With Overall Response	9 Participants	8 Participants

Adverse Events

Arm 1 - Pembrolizumab Monotherapy

Serious events: 15 serious events

Other events: 34 other events

Deaths: 25 deaths

Arm 2 - Acalabrutinib+Pembrolizumab

Serious events: 23 serious events

Other events: 39 other events

Deaths: 31 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

Measure	Arm 1 - Pembrolizumab Monotherapy n=35 participants at risk Arm 1: Pembrolizumab 200mg administered as an intravenous (IV) infusion every 3 weeks (Q3W)	Arm 2 - Acalabrutinib+Pembrolizumab n=40 participants at risk Arm 2: Acalabrutinib 100mg PO BID plus Pembrolizumab 200mg administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Blood and lymphatic system disorders Anaemia	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Cardiac disorders Coronary Artery Disease	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Gastrointestinal disorders Nausea	5.7% 2/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Gastrointestinal disorders Ascites	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	5.0% 2/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Gastrointestinal disorders Vomiting	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Gastrointestinal disorders Autoimmune Colitis	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Gastrointestinal disorders Colitis	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Gastrointestinal disorders Diarrhea	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Gastrointestinal disorders Duodenitis	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Gastrointestinal disorders Gastritis	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Gastrointestinal disorders Haematemesis	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Gastrointestinal disorders Impaired Gastric Emptying	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Gastrointestinal disorders Pneumoperitoneum	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Gastrointestinal disorders Rectal Hemorrhage	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
General disorders Fatigue	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
General disorders Pyrexia	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
General disorders Pain	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Hepatobiliary disorders Autoimmune Hepatitis	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Hepatobiliary disorders Hepatic Failure	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Hepatobiliary disorders Immune-Mediated Hepatitis	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Infections and infestations Sepsis	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	7.5% 3/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Infections and infestations Urinary Tract Infection	5.7% 2/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	5.0% 2/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Infections and infestations Pneumonia	5.7% 2/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Infections and infestations Cellulitis	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Infections and infestations Clostridium Difficile Colitis	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Infections and infestations Lower Respiratory Tract Infection	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Infections and infestations Peritonitis Bacterial	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Infections and infestations Systemic Candida	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Infections and infestations Urosepsis	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Injury, poisoning and procedural complications Femur Fracture	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Injury, poisoning and procedural complications Infusion Related Reaction	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Injury, poisoning and procedural complications Radiation Proctitis	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Investigations Alanine Aminotransferase Increased	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Investigations Aspartate Aminotransferase	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Metabolism and nutrition disorders Dehydration	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Metabolism and nutrition disorders Failure to Thrive	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Metabolism and nutrition disorders Hyperkalaemia	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Metabolism and nutrition disorders Hyponatraemia	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Musculoskeletal and connective tissue disorders Arthralgia	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Musculoskeletal and connective tissue disorders Back Pain	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Musculoskeletal and connective tissue disorders Bone Pain	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Musculoskeletal and connective tissue disorders Groin Pain	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Neoplasm Progression	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Liver	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Nervous system disorders Spinal Cord Compression	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Nervous system disorders Syncope	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Psychiatric disorders Delirium	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Renal and urinary disorders Acute Kidney Disease	5.7% 2/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	12.5% 5/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Renal and urinary disorders Haematuria	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	5.0% 2/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Renal and urinary disorders Urinary Tract Obstruction	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Renal and urinary disorders Hydronephrosis	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Respiratory, thoracic and mediastinal disorders Pulmonary Alveolar Hemorrhage	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Respiratory, thoracic and mediastinal disorders Pulmonary Oedema	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	2.5% 1/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.
Vascular disorders Deep Vein Thrombosis	2.9% 1/35 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.	0.00% 0/40 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 730.