Phase II Trial of Pembrolizumab With Trastuzumab and Chemotherapy in Advanced HER2 Positive Esophagogastric (EG) Cancer

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ClinicalTrials.gov Identifier: NCT02954536

Recruitment Status : Completed

First Posted : November 3, 2016

Results First Posted : February 9, 2023

Last Update Posted : March 16, 2023

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Sponsor:

Information provided by (Responsible Party):

Memorial Sloan Kettering Cancer Center

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Esophageal Cancer Gastric Cancer
Interventions	Drug: pembrolizumab Drug: trastuzumab Drug: capecitabine Drug: cisplatin Drug: Oxaliplatin Drug: 5-Fluorouracil
Enrollment	37

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Pembrolizumab, Trastuzumab,Capecitabine/Cisplatin
Arm/Group Description	Pembrolizumab 200 mg IV every 3 wee...
Arm/Group Description	Pembrolizumab 200 mg IV every 3 weeks, trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) IV every 3 weeks with cisplatin IV every 3 weeks with oral capecitabine 2 weeks on/1 week off. Each cycle consists of 21 days. Treatment will be administered on an outpatient basis. In Cycle 1, patients will initiate therapy with trastuzumab 8 mg/kg IV with pembrolizumab 200 mg IV. CT/MRI scan will be performed after the initial 3 weeks (1 cycle) to determine response to pembrolizumab and trastuzumab combination. With subsequent cycles, all patients will begin systemic chemotherapy with the capecitabine/cisplatin regimen in addition to pembrolizumab 200 mg IV with trastuzumab 6 mg/kg maintenance. Patients will receive cisplatin 80 mg/m2 IV on Day 1, and capecitabine 850mg/m2 twice a day on Days 1 through 14, every 3 weeks.
Period Title: Overall Study
Started	37
Completed	23
Not Completed	14
Reason Not Completed
Adverse Event	2
Death	12

Baseline Characteristics

Arm/Group Title		Pembrolizumab, Trastuzumab,Capecitabine/Cisplatin
Arm/Group Description		Pembrolizumab 200 mg IV every 3 wee...
Arm/Group Description		Pembrolizumab 200 mg IV every 3 weeks, trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) IV every 3 weeks with cisplatin IV every 3 weeks with oral capecitabine 2 weeks on/1 week off. Each cycle consists of 21 days. Treatment will be administered on an outpatient basis. In Cycle 1, patients will initiate therapy with trastuzumab 8 mg/kg IV with pembrolizumab 200 mg IV. CT/MRI scan will be performed after the initial 3 weeks (1 cycle) to determine response to pembrolizumab and trastuzumab combination. With subsequent cycles, all patients will begin systemic chemotherapy with the capecitabine/cisplatin regimen in addition to pembrolizumab 200 mg IV with trastuzumab 6 mg/kg maintenance. Patients will receive cisplatin 80 mg/m2 IV on Day 1, and capecitabine 850mg/m2 twice a day on Days 1 through 14, every 3 weeks.
Overall Number of Baseline Participants		37
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	37 participants
		60 (21 to 84)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	37 participants
	Female	29 78.4%
	Male	8 21.6%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	37 participants
	Hispanic or Latino	1 2.7%
	Not Hispanic or Latino	36 97.3%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	37 participants
	American Indian or Alaska Native	0 0.0%
	Asian	2 5.4%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	3 8.1%
	White	32 86.5%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants
United States	Number Analyzed	37 participants
United States		37 100.0%

Outcome Measures

1.Primary Outcome


Title	Percentage of Participants With Progression Free Survival
Description	We will define progression of disease per RECIST 1.1 criteria
Description	We will define progression of disease per RECIST 1.1 criteria
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Pembrolizumab, Trastuzumab,Capecitabine/Cisplatin
Arm/Group Description:	Pembrolizumab 200 mg IV every 3 wee...
Arm/Group Description:	Pembrolizumab 200 mg IV every 3 weeks, trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) IV every 3 weeks with cisplatin IV every 3 weeks with oral capecitabine 2 weeks on/1 week off. Each cycle consists of 21 days. Treatment will be administered on an outpatient basis. In Cycle 1, patients will initiate therapy with trastuzumab 8 mg/kg IV with pembrolizumab 200 mg IV. CT/MRI scan will be performed after the initial 3 weeks (1 cycle) to determine response to pembrolizumab and trastuzumab combination. With subsequent cycles, all patients will begin systemic chemotherapy with the capecitabine/cisplatin regimen in addition to pembrolizumab 200 mg IV with trastuzumab 6 mg/kg maintenance. Patients will receive cisplatin 80 mg/m2 IV on Day 1, and capecitabine 850mg/m2 twice a day on Days 1 through 14, every 3 weeks.
Overall Number of Participants Analyzed	37
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants with PRS
	70 (54 to 83)

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Pembrolizumab, Trastuzumab,Capecitabine/Cisplatin
Arm/Group Description	Pembrolizumab 200 mg IV every 3 wee...
Arm/Group Description	Pembrolizumab 200 mg IV every 3 weeks, trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) IV every 3 weeks with cisplatin IV every 3 weeks with oral capecitabine 2 weeks on/1 week off. Each cycle consists of 21 days. Treatment will be administered on an outpatient basis. In Cycle 1, patients will initiate therapy with trastuzumab 8 mg/kg IV with pembrolizumab 200 mg IV. CT/MRI scan will be performed after the initial 3 weeks (1 cycle) to determine response to pembrolizumab and trastuzumab combination. With subsequent cycles, all patients will begin systemic chemotherapy with the capecitabine/cisplatin regimen in addition to pembrolizumab 200 mg IV with trastuzumab 6 mg/kg maintenance. Patients will receive cisplatin 80 mg/m2 IV on Day 1, and capecitabine 850mg/m2 twice a day on Days 1 through 14, every 3 weeks.
All-Cause Mortality
	Pembrolizumab, Trastuzumab,Capecitabine/Cisplatin
	Affected / at Risk (%)
Total	12/37 (32.43%)
Serious Adverse Events Serious Adverse Events
	Pembrolizumab, Trastuzumab,Capecitabine/Cisplatin
	Affected / at Risk (%)
Total	2/37 (5.41%)
Renal and urinary disorders
Nephritis ^†	2/37 (5.41%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Pembrolizumab, Trastuzumab,Capecitabine/Cisplatin
	Affected / at Risk (%)
Total	36/37 (97.30%)
Blood and lymphatic system disorders
Anemia ^†	30/37 (81.08%)
Cardiac disorders
Decreased ejection fraction ^†	4/37 (10.81%)
Gastrointestinal disorders
Nausea ^†	31/37 (83.78%)
Diarrhea ^†	27/37 (72.97%)
Vomiting ^†	25/37 (67.57%)
Abdominal pain ^†	16/37 (43.24%)
Oral Mucositis ^†	12/37 (32.43%)
Colitis ^†	1/37 (2.70%)
General disorders
Fatigue ^†	33/37 (89.19%)
Investigations
Increased ALT or AST ^†	22/37 (59.46%)
Decreased platelet count ^†	22/37 (59.46%)
Decreased lymphocyte count ^†	22/37 (59.46%)
Decreased while blood cell count ^†	16/37 (43.24%)
Weight loss ^†	14/37 (37.84%)
Increased blood bilirubin ^†	8/37 (21.62%)
Decreased neutrophil ^†	7/37 (18.92%)
Metabolism and nutrition disorders
Hyperglycemia ^†	33/37 (89.19%)
Hypokalaemia, hypomagnesaemia, or hyponatraemia ^†	28/37 (75.68%)
Anorexia ^†	18/37 (48.65%)
Nervous system disorders
Parasthesis ^†	36/37 (97.30%)
Headache ^†	10/37 (27.03%)
Respiratory, thoracic and mediastinal disorders
Cough ^†	17/37 (45.95%)
Skin and subcutaneous tissue disorders
Dry skin ^†	16/37 (43.24%)
Palmar-plantar erythrodysesthesia syndrome ^†	8/37 (21.62%)
Vascular disorders
Limb edema ^†	10/37 (27.03%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Dr. Yelena Janjigian,MD
Organization:	Memorial Sloan Kettering Cancer Center
Phone:	646-888-4186
EMail:	janjigiy@mskcc.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Janjigian YY, Maron SB, Chatila WK, Millang B, Chavan SS, Alterman C, Chou JF, Segal MF, Simmons MZ, Momtaz P, Shcherba M, Ku GY, Zervoudakis A, Won ES, Kelsen DP, Ilson DH, Nagy RJ, Lanman RB, Ptashkin RN, Donoghue MTA, Capanu M, Taylor BS, Solit DB, Schultz N, Hechtman JF. First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2020 Jun;21(6):821-831. doi: 10.1016/S1470-2045(20)30169-8. Epub 2020 May 18.

Layout table for additonal information

Responsible Party:	Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT02954536
Other Study ID Numbers:	16-937
First Submitted:	November 2, 2016
First Posted:	November 3, 2016
Results First Submitted:	January 13, 2023
Results First Posted:	February 9, 2023
Last Update Posted:	March 16, 2023

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