Pembrolizumab Alone and In Combination With Acalabrutinib (ACP-196) in Subjects With Advanced Non-small Cell Lung Cancer (KEYNOTE166)

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ClinicalTrials.gov Identifier: NCT02448303

Recruitment Status : Completed

First Posted : May 19, 2015

Results First Posted : September 12, 2019

Last Update Posted : September 12, 2019

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

Merck Sharp & Dohme LLC

Information provided by (Responsible Party):

Acerta Pharma BV

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Carcinoma, Non-Small-Cell Lung
Interventions	Drug: Pembrolizumab Drug: Acalabrutinib
Enrollment	74

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Arm 1 - Pembrolizumab Monotherapy	Arm 2 - Acalabrutinib + Pembrolizumab
Arm/Group Description	Pembrolizumab 200mg administered as...	Acalabrutinib 100mg PO BID plus Pem...
Arm/Group Description	Pembrolizumab 200mg administered as an intravenous (IV) infusion every 3 weeks (Q3W).	Acalabrutinib 100mg PO BID plus Pembrolizumab 200mg administered as an intravenous (IV) infusion every 3 weeks (Q3W).
Period Title: Overall Study
Started	38	36
Enrolled	38	36
Received Study Medication	33	35
Discontinued Study	38	36
Completed	0	0
Not Completed	38	36

Baseline Characteristics

Arm/Group Title		Arm 1 - Pembrolizumab Monotherapy	Arm 2 - Acalabrutinib + Pembrolizumab	Total
Arm/Group Description		Pembrolizumab 200mg administered as...	Acalabrutinib 100mg PO BID plus Pem...	Total of all reporting groups
Arm/Group Description		Pembrolizumab 200mg administered as an intravenous (IV) infusion every 3 weeks (Q3W).	Acalabrutinib 100mg PO BID plus Pembrolizumab 200mg administered as an intravenous (IV) infusion every 3 weeks (Q3W).	Total of all reporting groups
Overall Number of Baseline Participants		33	35	68
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	33 participants	35 participants	68 participants
		63.7 (10.2)	64.6 (9.33)	64.2 (9.70)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	33 participants	35 participants	68 participants
	Female	15 45.5%	20 57.1%	35 51.5%
	Male	18 54.5%	15 42.9%	33 48.5%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	33 participants	35 participants	68 participants
	Hispanic or Latino	1 3.0%	1 2.9%	2 2.9%
	Not Hispanic or Latino	32 97.0%	34 97.1%	66 97.1%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	33 participants	35 participants	68 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	2 6.1%	4 11.4%	6 8.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	4 12.1%	4 11.4%	8 11.8%
	White	25 75.8%	27 77.1%	52 76.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	2 6.1%	0 0.0%	2 2.9%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	33 participants	35 participants	68 participants
United States		33	35	68

Outcome Measures

1.Primary Outcome


Title	Number of Participants With Overall Response
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1...
Description	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
Time Frame	Every 12 weeks for up to 2 years

Outcome Measure Data

Analysis Population Description

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.


Arm/Group Title	Arm 1 - Pembrolizumab Monotherapy	Arm 2 - Acalabrutinib + Pembrolizumab
Arm/Group Description:	Pembrolizumab 200mg administered as...	Acalabrutinib 100mg PO BID plus Pem...
Arm/Group Description:	Pembrolizumab 200mg administered as an intravenous (IV) infusion every 3 weeks (Q3W).	Acalabrutinib 100mg PO BID plus Pembrolizumab 200mg administered as an intravenous (IV) infusion every 3 weeks (Q3W).
Overall Number of Participants Analyzed	31	28
Measure Type: Count of Participants Unit of Measure: Participants
	4 12.9%	4 14.3%

Adverse Events

Time Frame	Safety Analysis tracked from 0 day to 2 years.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Arm 1 - Pembrolizumab Monotherapy	Arm 2 - Acalabrutinib + Pembrolizumab
Arm/Group Description	Pembrolizumab 200mg administered as...	Acalabrutinib 100mg PO BID plus Pem...
Arm/Group Description	Pembrolizumab 200mg administered as an intravenous (IV) infusion every 3 weeks (Q3W).	Acalabrutinib 100mg PO BID plus Pembrolizumab 200mg administered as an intravenous (IV) infusion every 3 weeks (Q3W).
All-Cause Mortality
	Arm 1 - Pembrolizumab Monotherapy	Arm 2 - Acalabrutinib + Pembrolizumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	18/33 (54.55%)	23/35 (65.71%)
Serious Adverse Events Serious Adverse Events
	Arm 1 - Pembrolizumab Monotherapy	Arm 2 - Acalabrutinib + Pembrolizumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	12/33 (36.36%)	18/35 (51.43%)
Blood and lymphatic system disorders
Anaemia ^†	1/33 (3.03%)	1/35 (2.86%)
Pancytopenia ^†	0/33 (0.00%)	1/35 (2.86%)
Cardiac disorders
Atrial Fibrillation ^†	0/33 (0.00%)	1/35 (2.86%)
Gastrointestinal disorders
Dysphagia ^†	2/33 (6.06%)	1/35 (2.86%)
Vomiting ^†	0/33 (0.00%)	1/35 (2.86%)
Gastrointestinal Haemorrhage ^†	1/33 (3.03%)	0/35 (0.00%)
Large Intestine Haemorrhage ^†	1/33 (3.03%)	0/35 (0.00%)
Nausea ^†	0/33 (0.00%)	1/35 (2.86%)
Stomatitis ^†	1/33 (3.03%)	0/35 (0.00%)
General disorders
Asthenia ^† [1]	1/33 (3.03%)	0/35 (0.00%)
Pain ^† [1]	0/33 (0.00%)	1/35 (2.86%)
Hepatobiliary disorders
Bile Duct Obstructions ^†	0/33 (0.00%)	1/35 (2.86%)
Infections and infestations
Pneumonia ^†	1/33 (3.03%)	3/35 (8.57%)
Cellulitis ^†	0/33 (0.00%)	1/35 (2.86%)
Clostridium Difficile Colitis ^†	0/33 (0.00%)	1/35 (2.86%)
Oral Candidiasis ^†	1/33 (3.03%)	0/35 (0.00%)
Pneumonia Viral ^†	0/33 (0.00%)	1/35 (2.86%)
Metabolism and nutrition disorders
Dehydration ^†	2/33 (6.06%)	1/35 (2.86%)
Failure to Thrive ^†	0/33 (0.00%)	1/35 (2.86%)
Musculoskeletal and connective tissue disorders
Arthralgia ^†	0/33 (0.00%)	1/35 (2.86%)
Pathological Fracture ^†	1/33 (3.03%)	0/35 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to Central Nervous System ^†	0/33 (0.00%)	1/35 (2.86%)
Nervous system disorders
Syncope ^†	1/33 (3.03%)	1/35 (2.86%)
Headache ^†	1/33 (3.03%)	0/35 (0.00%)
Tremor ^†	0/33 (0.00%)	1/35 (2.86%)
Psychiatric disorders
Mental Status Changes ^†	1/33 (3.03%)	1/35 (2.86%)
Renal and urinary disorders
Acute Kidney Injury ^†	1/33 (3.03%)	0/35 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^†	1/33 (3.03%)	4/35 (11.43%)
Hypoxia ^†	2/33 (6.06%)	1/35 (2.86%)
Pneumonitis ^†	2/33 (6.06%)	0/35 (0.00%)
Acute Respiratory Failure ^†	0/33 (0.00%)	1/35 (2.86%)
Asthma ^†	1/33 (3.03%)	0/35 (0.00%)
Chronic Obstructive Pulmonary Disease ^†	0/33 (0.00%)	1/35 (2.86%)
Haemoptysis ^†	0/33 (0.00%)	1/35 (2.86%)
Pleural Effusion ^†	0/33 (0.00%)	1/35 (2.86%)
Pneumonia Aspiration ^†	0/33 (0.00%)	1/35 (2.86%)
Pulmonary Embolism ^†	1/33 (3.03%)	0/35 (0.00%)
Respiratory Failure ^†	0/33 (0.00%)	1/35 (2.86%)
Skin and subcutaneous tissue disorders
Rash Maculo-Papular ^†	0/33 (0.00%)	1/35 (2.86%)
Vascular disorders
Haematoma ^†	0/33 (0.00%)	1/35 (2.86%)
Orthostatic Hypotension ^†	1/33 (3.03%)	0/35 (0.00%)
† Indicates events were collected by systematic assessment [1] General Disorders and Administration Site Conditions.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm 1 - Pembrolizumab Monotherapy	Arm 2 - Acalabrutinib + Pembrolizumab
	Affected / at Risk (%)	Affected / at Risk (%)
Total	33/33 (100.00%)	35/35 (100.00%)
Blood and lymphatic system disorders
Anaemia ^†	5/33 (15.15%)	9/35 (25.71%)
Ear and labyrinth disorders
Ear Pain ^†	2/33 (6.06%)	0/35 (0.00%)
Tinnitus ^†	0/33 (0.00%)	2/35 (5.71%)
Endocrine disorders
Hypothyroidism ^†	2/33 (6.06%)	2/35 (5.71%)
Eye disorders
Diplopia ^†	0/33 (0.00%)	2/35 (5.71%)
Gastrointestinal disorders
Diarrhea ^†	7/33 (21.21%)	11/35 (31.43%)
Nausea ^†	5/33 (15.15%)	12/35 (34.29%)
Vomiting ^†	3/33 (9.09%)	13/35 (37.14%)
Constipation ^†	3/33 (9.09%)	7/35 (20.00%)
Dry Mouth ^†	3/33 (9.09%)	5/35 (14.29%)
Abdominal Pain Upper ^†	1/33 (3.03%)	4/35 (11.43%)
Gastrooesophageal Reflux Disease ^†	2/33 (6.06%)	2/35 (5.71%)
Abdominal Discomfort ^†	0/33 (0.00%)	3/35 (8.57%)
Dysphagia ^†	0/33 (0.00%)	3/35 (8.57%)
Oesophagitis ^†	1/33 (3.03%)	2/35 (5.71%)
Stomatitis ^†	1/33 (3.03%)	2/35 (5.71%)
General disorders
Fatigue ^† [1]	15/33 (45.45%)	9/35 (25.71%)
Oedema Peripheral ^† [1]	5/33 (15.15%)	7/35 (20.00%)
Pyrexia ^† [1]	3/33 (9.09%)	4/35 (11.43%)
Non-Cardiac Chest Pain ^† [1]	1/33 (3.03%)	5/35 (14.29%)
Asthenia ^† [1]	0/33 (0.00%)	2/35 (5.71%)
Chest Pain ^† [1]	2/33 (6.06%)	0/35 (0.00%)
Chills ^† [1]	1/33 (3.03%)	3/35 (8.57%)
Mucosal Inflammation ^† [1]	2/33 (6.06%)	0/35 (0.00%)
Pain ^† [1]	1/33 (3.03%)	2/35 (5.71%)
Immune system disorders
Seasonal Allergy ^†	2/33 (6.06%)	1/35 (2.86%)
Infections and infestations
Upper Respiratory Tract Infection ^†	1/33 (3.03%)	5/35 (14.29%)
Pneumonia ^†	2/33 (6.06%)	2/35 (5.71%)
Urinary Tract Infection ^†	2/33 (6.06%)	2/35 (5.71%)
Oral Candidiasis ^†	2/33 (6.06%)	2/35 (5.71%)
Bronchitis ^†	2/33 (6.06%)	1/35 (2.86%)
Nasopharyngitis ^†	3/33 (9.09%)	0/35 (0.00%)
Sinusitis ^†	0/33 (0.00%)	2/35 (5.71%)
Injury, poisoning and procedural complications
Contusion ^†	0/33 (0.00%)	3/35 (8.57%)
Investigations
Aspartate Aminotransferase Increased ^†	2/33 (6.06%)	5/35 (14.29%)
Weight Decreased ^†	3/33 (9.09%)	5/35 (14.29%)
Blood Creatinine Increased ^†	2/33 (6.06%)	4/35 (11.43%)
Alanine Aminotransferase Increased ^†	0/33 (0.00%)	3/35 (8.57%)
Electrocardiogram QT Prolonged ^†	1/33 (3.03%)	3/35 (8.57%)
Lymphocyte Count Decreased ^†	1/33 (3.03%)	2/35 (5.71%)
Amylase Increased ^†	2/33 (6.06%)	0/35 (0.00%)
Weight Increased ^†	2/33 (6.06%)	0/35 (0.00%)
Metabolism and nutrition disorders
Decreased Appetite ^†	6/33 (18.18%)	12/35 (34.29%)
Dehydration ^†	6/33 (18.18%)	6/35 (17.14%)
Hyponatraemia ^†	3/33 (9.09%)	5/35 (14.29%)
Hyperglycaemia ^†	3/33 (9.09%)	3/35 (8.57%)
Hypokalaemia ^†	3/33 (9.09%)	2/35 (5.71%)
Hypomagnesaemia ^†	4/33 (12.12%)	1/35 (2.86%)
Hypoalbuminaemia ^†	2/33 (6.06%)	0/35 (0.00%)
Hypoalbuminaemia ^†	1/33 (3.03%)	2/35 (5.71%)
Hypercalcaemia ^†	2/33 (6.06%)	1/35 (2.86%)
Hypocalcaemia ^†	2/33 (6.06%)	1/35 (2.86%)
Hypophosphataemia ^†	2/33 (6.06%)	1/35 (2.86%)
Hyperuricaemia ^†	2/33 (6.06%)	0/35 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^†	3/33 (9.09%)	7/35 (20.00%)
Back Pain ^†	3/33 (9.09%)	4/35 (11.43%)
Musculoskeletal Pain ^†	3/33 (9.09%)	4/35 (11.43%)
Myalgia ^†	2/33 (6.06%)	3/35 (8.57%)
Pain in Extremity ^†	2/33 (6.06%)	3/35 (8.57%)
Muscular Weakness ^†	1/33 (3.03%)	3/35 (8.57%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Pain ^†	2/33 (6.06%)	0/35 (0.00%)
Nervous system disorders
Dizziness ^†	4/33 (12.12%)	7/35 (20.00%)
Headache ^†	6/33 (18.18%)	6/35 (17.14%)
Dysgeusia ^†	2/33 (6.06%)	2/35 (5.71%)
Neuropathy Peripheral ^†	3/33 (9.09%)	1/35 (2.86%)
Somnolence ^†	1/33 (3.03%)	2/35 (5.71%)
Psychiatric disorders
Anxiety ^†	2/33 (6.06%)	4/35 (11.43%)
Depression ^†	2/33 (6.06%)	3/35 (8.57%)
Insomnia ^†	1/33 (3.03%)	3/35 (8.57%)
Confusional State ^†	1/33 (3.03%)	2/35 (5.71%)
Sleep Disorder ^†	0/33 (0.00%)	2/35 (5.71%)
Renal and urinary disorders
Acute Kidney Injury ^†	2/33 (6.06%)	4/35 (11.43%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^†	8/33 (24.24%)	11/35 (31.43%)
Cough ^†	6/33 (18.18%)	10/35 (28.57%)
Wheezing ^†	5/33 (15.15%)	3/35 (8.57%)
Oropharyngeal Pain ^†	4/33 (12.12%)	1/35 (2.86%)
Pleural Effusion ^†	1/33 (3.03%)	4/35 (11.43%)
Productive Cough ^†	3/33 (9.09%)	2/35 (5.71%)
Epistaxis ^†	1/33 (3.03%)	2/35 (5.71%)
Hypoxia ^†	2/33 (6.06%)	2/35 (5.71%)
Haemoptysis ^†	0/33 (0.00%)	3/35 (8.57%)
Upper-Airway Cough Syndrome ^†	1/33 (3.03%)	2/35 (5.71%)
Sinus Congestion ^†	2/33 (6.06%)	0/35 (0.00%)
Rash Maculo-Papular ^†	1/33 (3.03%)	4/35 (11.43%)
Decubitus Ulcer ^†	1/33 (3.03%)	2/35 (5.71%)
Petechiae ^†	0/33 (0.00%)	3/35 (8.57%)
Skin and subcutaneous tissue disorders
Rash ^†	5/33 (15.15%)	3/35 (8.57%)
Dry Skin ^†	2/33 (6.06%)	3/35 (8.57%)
Rash Maculo-Papular ^†	1/33 (3.03%)	4/35 (11.43%)
Decubitus Ulcer ^†	1/33 (3.03%)	2/35 (5.71%)
Petechiae ^†	0/33 (0.00%)	3/35 (8.57%)
Purpura ^†	0/33 (0.00%)	2/35 (5.71%)
Vascular disorders
Hypotension ^†	2/33 (6.06%)	5/35 (14.29%)
Hypertension ^†	2/33 (6.06%)	4/35 (11.43%)
Hot Flush ^†	2/33 (6.06%)	0/35 (0.00%)
† Indicates events were collected by systematic assessment [1] General Disorders & Administration Site Conditions.

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Priti Patel, MD, Executive Director - Head of Clinical Development
Organization:	Acerta Pharma, LLC
Phone:	1-888-292-9613
EMail:	acertamc@dlss.com

Layout table for additonal information

Responsible Party:	Acerta Pharma BV
ClinicalTrials.gov Identifier:	NCT02448303
Other Study ID Numbers:	ACE-ST-007
First Submitted:	May 14, 2015
First Posted:	May 19, 2015
Results First Submitted:	July 19, 2019
Results First Posted:	September 12, 2019
Last Update Posted:	September 12, 2019

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