Trial Outcomes & Findings for Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475 (NCT NCT03049618)

Last Updated: 2025-10-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

Up to 22 months

Results posted on

2025-10-22

Participant Flow

Recruitment for this study opened in March 2017 and closed in March 2021. All subjects were seen and treated in the medical clinics at the University of Southern California

Participant milestones

Participant milestones
Measure	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	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
Overall Study STARTED	25	17
Overall Study COMPLETED	23	15
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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	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
Overall Study Death	1	0
Overall Study Lack of Efficacy	1	2

Baseline Characteristics

Enrollment to lung cohort terminated early so no specimen was processed

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Head and Neck Cancer Cohort n=25 Participants 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	Non-Small Cell Lung Cancer Cohort n=17 Participants 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	Total n=42 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=25 Participants	0 Participants n=17 Participants	0 Participants n=42 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=25 Participants	13 Participants n=17 Participants	28 Participants n=42 Participants
Age, Categorical >=65 years	10 Participants n=25 Participants	4 Participants n=17 Participants	14 Participants n=42 Participants
Sex: Female, Male Female	5 Participants n=25 Participants	9 Participants n=17 Participants	14 Participants n=42 Participants
Sex: Female, Male Male	20 Participants n=25 Participants	8 Participants n=17 Participants	28 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=25 Participants	4 Participants n=17 Participants	10 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=25 Participants	13 Participants n=17 Participants	32 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=25 Participants	0 Participants n=17 Participants	0 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=25 Participants	0 Participants n=17 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Asian	5 Participants n=25 Participants	6 Participants n=17 Participants	11 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=25 Participants	0 Participants n=17 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	2 Participants n=25 Participants	2 Participants n=17 Participants	4 Participants n=42 Participants
Race (NIH/OMB) White	17 Participants n=25 Participants	8 Participants n=17 Participants	25 Participants n=42 Participants
Race (NIH/OMB) More than one race	0 Participants n=25 Participants	0 Participants n=17 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=25 Participants	1 Participants n=17 Participants	2 Participants n=42 Participants
Region of Enrollment United States	25 Participants n=25 Participants	17 Participants n=17 Participants	42 Participants n=42 Participants
Smoking Status Never Smoke	12 Participants n=25 Participants	9 Participants n=17 Participants	21 Participants n=42 Participants
Smoking Status Former Smoker	11 Participants n=25 Participants	7 Participants n=17 Participants	18 Participants n=42 Participants
Smoking Status Current Smoker	2 Participants n=25 Participants	0 Participants n=17 Participants	2 Participants n=42 Participants
Smoking Status Unknown	0 Participants n=25 Participants	1 Participants n=17 Participants	1 Participants n=42 Participants
ECOG Performance Status (PS) Status 0 (Fully active without restriction)	12 Participants n=25 Participants	6 Participants n=17 Participants	18 Participants n=42 Participants
ECOG Performance Status (PS) Status 1 (Physically restricted but ambulatory and able to carry out light work)	13 Participants n=25 Participants	11 Participants n=17 Participants	24 Participants n=42 Participants
Site of Disease Larynx	4 Participants n=25 Participants	0 Participants n=17 Participants	4 Participants n=42 Participants
Site of Disease Lip and Oral Cavity	14 Participants n=25 Participants	0 Participants n=17 Participants	14 Participants n=42 Participants
Site of Disease Nasal Cavity and Paranasal Sinuses	5 Participants n=25 Participants	0 Participants n=17 Participants	5 Participants n=42 Participants
Site of Disease Pharynx	2 Participants n=25 Participants	0 Participants n=17 Participants	2 Participants n=42 Participants
Site of Disease Lung - Bronchi, NOS	0 Participants n=25 Participants	10 Participants n=17 Participants	10 Participants n=42 Participants
Site of Disease Lung - Lower Lobe	0 Participants n=25 Participants	4 Participants n=17 Participants	4 Participants n=42 Participants
Site of Disease Lung - Middle Lobe	0 Participants n=25 Participants	1 Participants n=17 Participants	1 Participants n=42 Participants
Site of Disease Lung - Upper Lobe	0 Participants n=25 Participants	2 Participants n=17 Participants	2 Participants n=42 Participants
Received Prior Surgery Yes	11 Participants n=25 Participants	5 Participants n=17 Participants	16 Participants n=42 Participants
Received Prior Surgery No	14 Participants n=25 Participants	12 Participants n=17 Participants	26 Participants n=42 Participants
Received Prior Radiotherapy Yes	17 Participants n=25 Participants	9 Participants n=17 Participants	26 Participants n=42 Participants
Received Prior Radiotherapy No	8 Participants n=25 Participants	8 Participants n=17 Participants	16 Participants n=42 Participants
Received Prior Chemotherapy Yes	20 Participants n=25 Participants	16 Participants n=17 Participants	36 Participants n=42 Participants
Received Prior Chemotherapy No	5 Participants n=25 Participants	1 Participants n=17 Participants	6 Participants n=42 Participants
Number of Prior Regimens Received 0	5 Participants n=25 Participants	1 Participants n=17 Participants	6 Participants n=42 Participants
Number of Prior Regimens Received 1	18 Participants n=25 Participants	10 Participants n=17 Participants	28 Participants n=42 Participants
Number of Prior Regimens Received 2	2 Participants n=25 Participants	5 Participants n=17 Participants	7 Participants n=42 Participants
Number of Prior Regimens Received 3	0 Participants n=25 Participants	1 Participants n=17 Participants	1 Participants n=42 Participants
HPV Status Negative	15 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed	0 Participants Enrollment to lung cohort terminated early so no specimen was processed	15 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed
HPV Status Positive	10 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed	0 Participants Enrollment to lung cohort terminated early so no specimen was processed	10 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed
P16 Gene Status Negative	15 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed	—	15 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed
P16 Gene Status Positive	10 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed	—	10 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed
EphrinB2 Status Negative	9 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed	0 Participants Enrollment to lung cohort terminated early so no specimen was processed	9 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed
EphrinB2 Status Positive	16 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed	0 Participants Enrollment to lung cohort terminated early so no specimen was processed	16 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed
PDL-1 Status Negative	13 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed	0 Participants Enrollment to lung cohort terminated early so no specimen was processed	13 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed
PDL-1 Status Positive	12 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed	0 Participants Enrollment to lung cohort terminated early so no specimen was processed	12 Participants n=25 Participants • Enrollment to lung cohort terminated early so no specimen was processed

PRIMARY outcome

Timeframe: Up to 22 months

Population: Evaluable population of patients who received at least 1 dose of therapy. No statistical analysis is performed.

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	Non-Small Cell Lung Cancer Cohort n=17 Participants 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
Overall Response Rate (ORR)	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 22 months

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=6 Participants 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	Non-Small Cell Lung Cancer Cohort n=17 Participants 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
Duration of Response	3.7 Months Interval 1.8 to 8.9	7.6 Months Interval 1.6 to 28.0

SECONDARY outcome

Timeframe: 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).

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

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.

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	Non-Small Cell Lung Cancer Cohort n=17 Participants 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
Number of Participants With Adverse Events CTCAE grade 1 or 2	25 participants	17 participants
Number of Participants With Adverse Events CTCAE grade 3 or 4	23 participants	17 participants

SECONDARY outcome

Timeframe: Up to 41 months

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

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	Non-Small Cell Lung Cancer Cohort n=17 Participants 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
Overall Survival (OS)	8.6 Months Interval 3.2 to 13.7	11.8 Months Interval 4.2 to 30.1

SECONDARY outcome

Timeframe: Up to 23 months

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

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.

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	Non-Small Cell Lung Cancer Cohort n=17 Participants 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
Progression Free Survival (PFS)	2.6 Months Interval 1.3 to 4.1	3.0 Months Interval 1.2 to 6.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 22 months

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

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.

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	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
Association of Biomarker With Overall Response Rate - HPV Status HPV Negative who achieved CR/PR	5 Participants	—
Association of Biomarker With Overall Response Rate - HPV Status HPV Positive who achieved CR/PR	1 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 22 months

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	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
Association of Biomarker With Overall Response Rate - P16 Status P16 Negative who achieved CR/PR	5 Participants	—
Association of Biomarker With Overall Response Rate - P16 Status P16 Positive who achieved CR/PR	1 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 22 months

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	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
Association of Biomarkers With Overall Response Rate - EphrinB2 Status EphrinB2 Negative who achieved CR/PR	9 Participants	—
Association of Biomarkers With Overall Response Rate - EphrinB2 Status EphrinB2 Positive who achieved CR/PR	6 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 22 months

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	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
Association of Biomarkers With Overall Response Rate - PD-L1 Status PD-L1 Negative who achieved CR/PR	3 Participants	—
Association of Biomarkers With Overall Response Rate - PD-L1 Status PD-L1 Positive who achieved CR/PR	3 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 22 months

Population: 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.

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=11 Participants 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	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
Association of Biomarkers With Overall Response Rate - EphrinB2 Positive/HPV-negative	5 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 34 months

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

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	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
Association of Biomarkers With Overall Survival (OS) - HPV Status HPV Negative	8.6 Months Interval 2.0 to 12.6	—
Association of Biomarkers With Overall Survival (OS) - HPV Status HPV Positive	7.0 Months Interval 1.5 to 28.8	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 34 months

Population: 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.

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	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
Association of Biomarkers With Overall Survival (OS) - P16 Status P16 Negative	8.6 Months Interval 2.0 to 12.6	—
Association of Biomarkers With Overall Survival (OS) - P16 Status P16 Positive	7.0 Months Interval 1.5 to 28.8	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 24 months

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

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	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
Association of Biomarkers With Overall Survival (OS) - EphrinB2 EphrinB2 Negative	7.0 Months Interval 0.3 to 14.4	—
Association of Biomarkers With Overall Survival (OS) - EphrinB2 EphrinB2 Positive	10.9 Months Interval 3.2 to 22.8	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 34 months

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

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	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
Association of Biomarkers With Overall Survival (OS) - PD-L1 Status PD-L1 Negative	12.3 Months Interval 2.8 to 34.0	—
Association of Biomarkers With Overall Survival (OS) - PD-L1 Status PD-L1 Positive	7.6 Months Interval 2.0 to 22.8	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 34 months

Population: 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.

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=11 Participants 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	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
Association of Biomarkers With Overall Survival (OS) - EphrinB2 Positive/HPV-negative	10.9 Months Interval 2.0 to 13.7	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 11 months

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

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	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
Association of Biomarkers With Progression Free Survival (PFS) - HPV Status HPV Negative	2.5 Months Interval 1.1 to 5.4	—
Association of Biomarkers With Progression Free Survival (PFS) - HPV Status HPV Positive	2.6 Months Interval 1.3 to 4.1	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 11 months

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

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	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
Association of Biomarkers With Progression Free Survival (PFS) - P16 Status P16 Negative	2.5 Months Interval 1.1 to 5.4	—
Association of Biomarkers With Progression Free Survival (PFS) - P16 Status P16 Positive	2.6 Months Interval 1.3 to 4.1	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 11 months

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

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	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
Association of Biomarkers With Progression Free Survival (PFS) - EphrinB2 Status EphrinB2 Negative	2.5 Months Interval 0.3 to 4.0	—
Association of Biomarkers With Progression Free Survival (PFS) - EphrinB2 Status EphrinB2 Positive	2.9 Months Interval 1.3 to 6.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 11 months

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

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=25 Participants 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	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
Association of Biomarkers With Progression Free Survival (PFS) - PD-L1 Status PD-L1 Negative	2.8 Months Interval 1.2 to 5.6	—
Association of Biomarkers With Progression Free Survival (PFS) - PD-L1 Status PD-L1 Positive	2.5 Months Interval 1.2 to 5.4	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 11 months

Population: 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.

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

Outcome measures

Outcome measures
Measure	Head and Neck Cancer Cohort n=11 Participants 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	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
Association of Biomarkers With Progression Free Survival (PFS) - EphrinB2 Positive/HPV-negative	3.2 Months Interval 1.1 to 7.3	—

Adverse Events

Head and Neck Cancer Cohort

Serious events: 12 serious events

Other events: 16 other events

Deaths: 12 deaths

Non-Small Cell Lung Cancer Cohort

Serious events: 8 serious events

Other events: 11 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Head and Neck Cancer Cohort n=25 participants at risk 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	Non-Small Cell Lung Cancer Cohort n=17 participants at risk 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
Blood and lymphatic system disorders Anemia	4.0% 1/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Gastrointestinal disorders Dysphagia	8.0% 2/25 • Up to 41 months	0.00% 0/17 • Up to 41 months
General disorders Fatigue	4.0% 1/25 • Up to 41 months	0.00% 0/17 • Up to 41 months
Investigations Alkaline Phosphatase Increased	4.0% 1/25 • Up to 41 months	0.00% 0/17 • Up to 41 months
Investigations Aspartate Aminotransferase Increased	8.0% 2/25 • Up to 41 months	0.00% 0/17 • Up to 41 months
Investigations Blood Bilirubin Increased	4.0% 1/25 • Up to 41 months	0.00% 0/17 • Up to 41 months
Metabolism and nutrition disorders Anorexia	8.0% 2/25 • Up to 41 months	0.00% 0/17 • Up to 41 months
Metabolism and nutrition disorders Hyponatremia	8.0% 2/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Musculoskeletal and connective tissue disorders Generalized Muscle Weakness	4.0% 1/25 • Up to 41 months	0.00% 0/17 • Up to 41 months
Nervous system disorders Headache	0.00% 0/25 • Up to 41 months	11.8% 2/17 • Up to 41 months
Respiratory, thoracic and mediastinal disorders Dyspnea	4.0% 1/25 • Up to 41 months	11.8% 2/17 • Up to 41 months
Vascular disorders Hypertension	36.0% 9/25 • Up to 41 months	35.3% 6/17 • Up to 41 months
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Gastrointestinal disorders Colonic Perforation	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Gastrointestinal disorders Pericolonic Abscess	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Nervous system disorders Stroke	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months

Other adverse events

Other adverse events
Measure	Head and Neck Cancer Cohort n=25 participants at risk 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	Non-Small Cell Lung Cancer Cohort n=17 participants at risk 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
Vascular disorders Hypertension	28.0% 7/25 • Up to 41 months	29.4% 5/17 • Up to 41 months
General disorders Fatigue	12.0% 3/25 • Up to 41 months	29.4% 5/17 • Up to 41 months
Investigations Alanine Aminotransferase Increased	8.0% 2/25 • Up to 41 months	11.8% 2/17 • Up to 41 months
Gastrointestinal disorders Constipation	4.0% 1/25 • Up to 41 months	17.6% 3/17 • Up to 41 months
Gastrointestinal disorders Nausea	4.0% 1/25 • Up to 41 months	35.3% 6/17 • Up to 41 months
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Nervous system disorders Headache	4.0% 1/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Skin and subcutaneous tissue disorders Pruritus	4.0% 1/25 • Up to 41 months	23.5% 4/17 • Up to 41 months
Skin and subcutaneous tissue disorders Rash Maculo-Papular	4.0% 1/25 • Up to 41 months	11.8% 2/17 • Up to 41 months
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/25 • Up to 41 months	23.5% 4/17 • Up to 41 months
Metabolism and nutrition disorders Anorexia	0.00% 0/25 • Up to 41 months	17.6% 3/17 • Up to 41 months
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/25 • Up to 41 months	11.8% 2/17 • Up to 41 months
Investigations Weight loss	0.00% 0/25 • Up to 41 months	17.6% 3/17 • Up to 41 months
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/25 • Up to 41 months	11.8% 2/17 • Up to 41 months
Nervous system disorders Dizziness	0.00% 0/25 • Up to 41 months	11.8% 2/17 • Up to 41 months
Investigations Alkaline Phosphatase Increased	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Investigations Creatinine Increased	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Metabolism and nutrition disorders Dehydration	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Gastrointestinal disorders Diarrhea	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Gastrointestinal disorders Dry mouth	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
General disorders Edema limbs	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Injury, poisoning and procedural complications Fall	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Musculoskeletal and connective tissue disorders Generalized Muscle Weakness	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Metabolism and nutrition disorders Hypokalemia	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Skin and subcutaneous tissue disorders Skin hypopigmentation	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months
Gastrointestinal disorders Stomach pain	0.00% 0/25 • Up to 41 months	5.9% 1/17 • Up to 41 months

Additional Information

Victoria Soto

University of Southern California

Phone: 323-865-3441

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place