Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, M... | NCT03049618

NCT03049618

Secondary IDs

ID	Type	Description	Link
NCI-2017-00189	Registry Identifier	CTRP (Clinical Trial Reporting Program)
0S-16-8	Other Identifier	USC / Norris Comprehensive Cancer Center
P30CA014089	U.S. NIH Grant/Contract		View source

Status Module

Sponsor/Collaborators Module

Name	Class
National Cancer Institute (NCI)	NIH

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Head and Neck Cancer Cohort	Experimental	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Biological: Recombinant EphB4-HSA Fusion Protein
Non-Small Cell Lung Cancer Cohort	Experimental	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Biological: Recombinant EphB4-HSA Fusion Protein

Name	Type	Description	Arm Group Labels	Other Names
Laboratory Biomarker Analysis	Other	Correlative studies	Head and Neck Cancer Cohort Non-Small Cell Lung Cancer Cohort

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Response Rate (ORR)	Calculated based on the evaluable population of patients who received at least 1 dose of therapy. Overall response rate (ORR) is complete response (CR) + partial response (PR) recorded from study entry until disease progression based on RECIST v1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.	Up to 22 months

Secondary Outcomes

Measure	Description	Time Frame
Duration of Response	Duration of response is measured from date of first confirmed response until date of disease progression.	Up to 22 months
Number of Participants With Adverse Events	The adverse events were graded as per common terminology criteria for adverse events(CTCAE) version 4.0. For a detailed list of adverse events refer to the adverse event module.

Other Outcomes

Measure	Description	Time Frame
Association of Biomarker With Overall Response Rate - HPV Status	Overall response rate (ORR) is complete response (CR) + partial response (PR) recorded from study entry until disease progression based on RECIST v1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

One of the following:
- Locally advanced or metastatic non-small cell lung cancer that has progressed after at least 1 line of platinum based chemotherapy
  - Patients may have received up to 2 prior lines of chemotherapy
  - Patients with actionable alterations in EGFR/ALK/ROS1/BRAF must also have progressed after treatment with a tyrosine kinase inhibitor appropriate for their genetic alteration
  - Untreated patients who refuse 1st line platinum based chemotherapy are also eligible
- Squamous cell carcinoma of the head and neck whose disease has progressed after at least 1 line of platinum based chemotherapy
  - Patients may have received up to 2 prior lines of chemotherapy
  - Untreated patients who refuse 1st line platinum based chemotherapy are also eligible
  - Patients who relapse within 6 months of adjuvant cisplatin based concurrent chemoradiation, or neoadjuvant cisplatin based therapy can be considered eligible without an additional course of platinum chemotherapy for relapsed disease
  - Patients may have either locally recurrent or distant metastatic disease
Be willing and able to provide written informed consent/assent for the trial
Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion after 2 cycles of therapy
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
Absolute neutrophil count (ANC) >= 1,500 /mcL
Platelets >= 100,000 / mcL
Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN
Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases
Albumin >= 2.5 mg/dL
International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
- Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy
- Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

Exclusion Criteria:

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
Has a known history of active TB (Bacillus tuberculosis)
Hypersensitivity to pembrolizumab or any of its excipients
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
- Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
- Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability; known brain metastases are considered active, if any of the following criteria is applicable:
- Brain imaging during screening demonstrates progression of existing metastases and/or appearance of new lesions compared to brain imaging performed at least 4 weeks earlier
- Neurological symptoms attributed to brain metastases have not returned to baseline
- Steroids were used for brain metastases within 28 days of randomization
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Has known history of, or any evidence of active, non-infectious pneumonitis
Has an active infection requiring systemic therapy
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
Has received a live vaccine within 30 days of planned start of study therapy
- Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

Contacts/Locations Module

Name	Affiliation	Role
Jorge Nieva, MD	University of Southern California	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
USC / Norris Comprehensive Cancer Center		Los Angeles	California	90033	United States

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Aug 6, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

All enrolled patients are included.

Arm/Group Information

ID	Title	Description
BG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
BG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00025 BG00117 BG00242

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	OG0006 OG0013

Secondary

Duration of Response

Duration of response is measured from date of first confirmed response until date of disease progression.

Posted

Median

95% Confidence Interval

Months

Up to 22 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Units	Counts
Participants

Secondary

Number of Participants With Adverse Events

The adverse events were graded as per common terminology criteria for adverse events(CTCAE) version 4.0. For a detailed list of adverse events refer to the adverse event module.

All enrolled patients are included. No statistical analysis is performed.

Posted

Number

participants

Adverse events were collected from first dose of study treatment up to 30 days after last dose of treatment, up to 21 months (number of treatment given ranged from 1 cycle to 30 cycles).

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Secondary

Overall Survival (OS)

OS is the duration from study entry to death. Participants last known to be alive are censored at date of last contact.

All enrolled patients are included. Statistical analysis was not performed.

Posted

Median

95% Confidence Interval

Months

Up to 41 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Units	Counts

Secondary

Progression Free Survival (PFS)

PFS was defined as duration of time from the first dose of study drug to the first documentation of Progressive Disease (PD) by investigator assessment using RECIST 1.1 or death on study due to any cause on or before the data cutoff date, whichever occurred first. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed, and disease is progressing, regardless of the status of the target lesions.

All patients were included in the analysis. Statistical analysis was not performed.

Posted

Median

95% Confidence Interval

Months

Up to 23 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarker With Overall Response Rate - HPV Status

Overall response rate (ORR) is complete response (CR) + partial response (PR) recorded from study entry until disease progression based on RECIST v1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Only the Head and Neck cancer cohort is being reported. No specimens were collected for the non-small cell lung cancer cohort.

Posted

Count of Participants

Participants

Up to 22 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarker With Overall Response Rate - P16 Status

Only the Head and Neck cancer cohort is being reported. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Count of Participants

Participants

Up to 22 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Overall Response Rate - EphrinB2 Status

Only the Head and Neck cancer cohort is being reported. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Count of Participants

Participants

Up to 22 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Overall Response Rate - PD-L1 Status

Only the Head and Neck cancer cohort is being reported. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Count of Participants

Participants

Up to 22 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Overall Response Rate - EphrinB2 Positive/HPV-negative

Only the Head and Neck cancer cohort is being reported. No statistical analysis performed. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Count of Participants

Participants

Up to 22 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Overall Survival (OS) - HPV Status

OS was calculated from study entry to date of death. Participants last known to be alive are censored at date of last contact.

Only the Head and Neck cancer cohort is being reported. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Median

95% Confidence Interval

Months

Up to 34 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Overall Survival (OS) - P16 Status

OS was calculated from study entry to date of death. Participants last known to be alive are censored at date of last contact.

Only the Head and Neck cancer cohort is being reported. 10 participants were P16-positive, 15 participants were P16-negative, for a total of 25 participants. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Median

95% Confidence Interval

Months

Up to 34 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Overall Survival (OS) - EphrinB2

OS was calculated from study entry to date of death. Participants last known to be alive are censored at date of last contact.

Only the Head and Neck cancer cohort is being reported. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Median

95% Confidence Interval

Months

Up to 24 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Overall Survival (OS) - PD-L1 Status

OS was calculated from study entry to date of death. Participants last known to be alive are censored at date of last contact.

Only the Head and Neck cancer cohort is being reported. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Median

95% Confidence Interval

Months

Up to 34 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Overall Survival (OS) - EphrinB2 Positive/HPV-negative

OS was calculated from study entry to date of death. Participants last known to be alive are censored at date of last contact.

Only the Head and Neck cancer cohort is being reported. No statistical analysis performed. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Median

95% Confidence Interval

Months

Up to 34 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Progression Free Survival (PFS) - HPV Status

From study entry to the date of first documented disease progression or death due to any cause, whichever came first.

Only the Head and Neck cancer cohort is being reported. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Median

95% Confidence Interval

Months

Up to 11 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Progression Free Survival (PFS) - P16 Status

From study entry to the date of first documented disease progression or death due to any cause, whichever came first.

Only the Head and Neck cancer cohort is being reported. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Median

95% Confidence Interval

Months

Up to 11 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Progression Free Survival (PFS) - EphrinB2 Status

From study entry to the date of first documented disease progression or death due to any cause, whichever came first.

Only the Head and Neck cancer cohort is being reported. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Median

95% Confidence Interval

Months

Up to 11 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Progression Free Survival (PFS) - PD-L1 Status

From study entry to the date of first documented disease progression or death due to any cause, whichever came first.

Only the Head and Neck cancer cohort is being reported. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Median

95% Confidence Interval

Months

Up to 11 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Other Pre-specified

Association of Biomarkers With Progression Free Survival (PFS) - EphrinB2 Positive/HPV-negative

From study entry to the date of first documented disease progression or death due to any cause, whichever came first.

Only the Head and Neck cancer cohort is being reported. No statistical analysis performed. No specimens were collected in the non-small cell lung cancer cohort.

Posted

Median

95% Confidence Interval

Months

Up to 11 months

ID	Title	Description
OG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV
OG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Head and Neck Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV	12	25	12	25	16	25
EG001	Non-Small Cell Lung Cancer Cohort	Patients receive pembrolizumab IV over 30 minutes on day 1 and recombinant EphB4-HSA fusion protein IV over 30 minutes on days 1, 8, and 15. Courses repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Recombinant EphB4-HSA Fusion Protein: Given IV	6	17	8	17	11	17

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0011 affected17 at risk
Dysphagia	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected25 at risk EG0010 affected17 at risk
Fatigue	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected17 at risk
Alkaline Phosphatase Increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected17 at risk
Aspartate Aminotransferase Increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0002 affected25 at risk EG0010 affected17 at risk
Blood Bilirubin Increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected17 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected25 at risk EG0010 affected17 at risk
Hyponatremia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected25 at risk EG0011 affected17 at risk
Generalized Muscle Weakness	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0010 affected17 at risk
Headache	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0012 affected17 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0012 affected17 at risk
Hypertension	Vascular disorders	CTCAE (4.0)	Systematic Assessment	EG0009 affected25 at risk EG0016 affected17 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Colonic Perforation	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Pericolonic Abscess	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Stroke	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertension	Vascular disorders	CTCAE (4.0)	Systematic Assessment	EG0007 affected25 at risk EG0015 affected17 at risk
Fatigue	General disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected25 at risk EG0015 affected17 at risk
Alanine Aminotransferase Increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0002 affected25 at risk EG0012 affected17 at risk
Constipation	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0013 affected17 at risk
Nausea	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0016 affected17 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0011 affected17 at risk
Headache	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0011 affected17 at risk
Pruritus	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0014 affected17 at risk
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected25 at risk EG0012 affected17 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0014 affected17 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0013 affected17 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0012 affected17 at risk
Weight loss	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0013 affected17 at risk
Back pain	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0012 affected17 at risk
Dizziness	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0012 affected17 at risk
Alkaline Phosphatase Increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Creatinine Increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Dehydration	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Dry mouth	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Edema limbs	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Fall	Injury, poisoning and procedural complications	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Generalized Muscle Weakness	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Hyperkalemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Skin hypopigmentation	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk
Stomach pain	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected25 at risk EG0011 affected17 at risk

First MCP Posted Date

ID	Term
D000077195	Squamous Cell Carcinoma of Head and Neck
D002289	Carcinoma, Non-Small-Cell Lung

Ancestor Terms

ID	Term
D002294	Carcinoma, Squamous Cell
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006258	Head and Neck Neoplasms
D009371	Neoplasms by Site
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
C582435	pembrolizumab

Units	Counts
Participants	OG00025 OG00117

Units	Counts
Participants	OG00025 OG0010

Units	Counts
Participants	OG00011 OG0010

Units	Counts
Participants	OG00011 OG0010