ALK Gene Mutation, BRAF Gene Mutation, EGFR Gene Mutation, Head and Neck Squamous Cell Carcinoma, Metastatic Head and Neck Carcinoma, Recurrent Head and Neck Carcinoma, Recurrent Non-Small Cell Lung Carcinoma, ROS1 Gene Mutation, Stage IIIA Non-Small Cell Lung Cancer, Stage IIIB Non-Small Cell Lung Cancer, Stage III Non-Small Cell Lung Cancer, Stage IV Non-Small Cell Lung Cancer
Conditions
Brief summary
This phase IIa trial studies how well recombinant EphB4-HSA fusion protein and pembrolizumab work in treating patients with non-small cell lung cancer that has spread to other places in the body or head and neck squamous cell cancer that has come back or spread to other places in the body. Recombinant EphB4-HSA fusion protein may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Giving recombinant EphB4-HSA fusion protein and pembrolizumab may work better in treating patients with non-small cell lung or head and neck squamous cell cancer.
Detailed description
PRIMARY OBJECTIVES: I. Determine the response rate of the combination of pembrolizumab and recombinant EphB4-HSA fusion protein (sEphB4-HSA) as combination therapy. SECONDARY OBJECTIVES: I. Determine the biomarkers of response. II. Determine the unique toxicities of the combination of pembrolizumab and sEphB4-HSA. OUTLINE: Patients receive pembrolizumab intravenously (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. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALPembrolizumab
Given IV
BIOLOGICALRecombinant EphB4-HSA Fusion Protein
Given IV
Sponsors
National Cancer Institute (NCI)
University of Southern California
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 22 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | Up to 22 months | Duration of response is measured from date of first confirmed response until date of disease progression. |
| Number of Participants With Adverse Events | 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). | 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. |
| Overall Survival (OS) | Up to 41 months | OS is the duration from study entry to death. Participants last known to be alive are censored at date of last contact. |
| Progression Free Survival (PFS) | Up to 23 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Association of Biomarkers With Overall Survival (OS) - HPV Status | Up to 34 months | OS was calculated from study entry to date of death. Participants last known to be alive are censored at date of last contact. |
| Association of Biomarkers With Overall Survival (OS) - P16 Status | Up to 34 months | OS was calculated from study entry to date of death. Participants last known to be alive are censored at date of last contact. |
| Association of Biomarkers With Overall Survival (OS) - EphrinB2 | Up to 24 months | OS was calculated from study entry to date of death. Participants last known to be alive are censored at date of last contact. |
| Association of Biomarkers With Overall Survival (OS) - PD-L1 Status | Up to 34 months | OS was calculated from study entry to date of death. Participants last known to be alive are censored at date of last contact. |
| Association of Biomarkers With Overall Survival (OS) - EphrinB2 Positive/HPV-negative | Up to 34 months | OS was calculated from study entry to date of death. Participants last known to be alive are censored at date of last contact. |
| Association of Biomarker With Overall Response Rate - HPV Status | Up to 22 months | 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. |
| Association of Biomarkers With Progression Free Survival (PFS) - P16 Status | Up to 11 months | From study entry to the date of first documented disease progression or death due to any cause, whichever came first. |
| Association of Biomarkers With Progression Free Survival (PFS) - EphrinB2 Status | Up to 11 months | From study entry to the date of first documented disease progression or death due to any cause, whichever came first. |
| Association of Biomarkers With Progression Free Survival (PFS) - PD-L1 Status | Up to 11 months | From study entry to the date of first documented disease progression or death due to any cause, whichever came first. |
| Association of Biomarkers With Progression Free Survival (PFS) - EphrinB2 Positive/HPV-negative | Up to 11 months | From study entry to the date of first documented disease progression or death due to any cause, whichever came first. |
| Association of Biomarkers With Progression Free Survival (PFS) - HPV Status | Up to 11 months | From study entry to the date of first documented disease progression or death due to any cause, whichever came first. |
| Association of Biomarker With Overall Response Rate - P16 Status | Up to 22 months | 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. |
| Association of Biomarkers With Overall Response Rate - EphrinB2 Status | Up to 22 months | 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. |
| Association of Biomarkers With Overall Response Rate - PD-L1 Status | Up to 22 months | 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. |
| Association of Biomarkers With Overall Response Rate - EphrinB2 Positive/HPV-negative | Up to 22 months | 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. |
Countries
United States
Participant flow
Recruitment details
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
Participants by arm
| Arm | Count |
|---|---|
| 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 | 25 |
| 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 | 17 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 2 |
Baseline characteristics
| Characteristic | Head and Neck Cancer Cohort | Non-Small Cell Lung Cancer Cohort | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 4 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 13 Participants | 28 Participants |
| ECOG Performance Status (PS) Status 0 (Fully active without restriction) | 12 Participants | 6 Participants | 18 Participants |
| ECOG Performance Status (PS) Status 1 (Physically restricted but ambulatory and able to carry out light work) | 13 Participants | 11 Participants | 24 Participants |
| EphrinB2 Status Negative | 9 Participants | 0 Participants | 9 Participants |
| EphrinB2 Status Positive | 16 Participants | 0 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 4 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 13 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HPV Status Negative | 15 Participants | 0 Participants | 15 Participants |
| HPV Status Positive | 10 Participants | 0 Participants | 10 Participants |
| Number of Prior Regimens Received 0 | 5 Participants | 1 Participants | 6 Participants |
| Number of Prior Regimens Received 1 | 18 Participants | 10 Participants | 28 Participants |
| Number of Prior Regimens Received 2 | 2 Participants | 5 Participants | 7 Participants |
| Number of Prior Regimens Received 3 | 0 Participants | 1 Participants | 1 Participants |
| P16 Gene Status Negative | 15 Participants | — | 15 Participants |
| P16 Gene Status Positive | 10 Participants | — | 10 Participants |
| PDL-1 Status Negative | 13 Participants | 0 Participants | 13 Participants |
| PDL-1 Status Positive | 12 Participants | 0 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 17 Participants | 8 Participants | 25 Participants |
| Received Prior Chemotherapy No | 5 Participants | 1 Participants | 6 Participants |
| Received Prior Chemotherapy Yes | 20 Participants | 16 Participants | 36 Participants |
| Received Prior Radiotherapy No | 8 Participants | 8 Participants | 16 Participants |
| Received Prior Radiotherapy Yes | 17 Participants | 9 Participants | 26 Participants |
| Received Prior Surgery No | 14 Participants | 12 Participants | 26 Participants |
| Received Prior Surgery Yes | 11 Participants | 5 Participants | 16 Participants |
| Region of Enrollment United States | 25 Participants | 17 Participants | 42 Participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 14 Participants |
| Sex: Female, Male Male | 20 Participants | 8 Participants | 28 Participants |
| Site of Disease Larynx | 4 Participants | 0 Participants | 4 Participants |
| Site of Disease Lip and Oral Cavity | 14 Participants | 0 Participants | 14 Participants |
| Site of Disease Lung - Bronchi, NOS | 0 Participants | 10 Participants | 10 Participants |
| Site of Disease Lung - Lower Lobe | 0 Participants | 4 Participants | 4 Participants |
| Site of Disease Lung - Middle Lobe | 0 Participants | 1 Participants | 1 Participants |
| Site of Disease Lung - Upper Lobe | 0 Participants | 2 Participants | 2 Participants |
| Site of Disease Nasal Cavity and Paranasal Sinuses | 5 Participants | 0 Participants | 5 Participants |
| Site of Disease Pharynx | 2 Participants | 0 Participants | 2 Participants |
| Smoking Status Current Smoker | 2 Participants | 0 Participants | 2 Participants |
| Smoking Status Former Smoker | 11 Participants | 7 Participants | 18 Participants |
| Smoking Status Never Smoke | 12 Participants | 9 Participants | 21 Participants |
| Smoking Status Unknown | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 25 | 6 / 17 |
| other Total, other adverse events | 16 / 25 | 11 / 17 |
| serious Total, serious adverse events | 12 / 25 | 8 / 17 |
Outcome results
Primary
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.
Time frame: Up to 22 months
Population: Evaluable population of patients who received at least 1 dose of therapy. No statistical analysis is performed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Head and Neck Cancer Cohort | Overall Response Rate (ORR) | 6 Participants |
| Non-Small Cell Lung Cancer Cohort | Overall Response Rate (ORR) | 3 Participants |
Secondary
Duration of Response
Duration of response is measured from date of first confirmed response until date of disease progression.
Time frame: Up to 22 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Head and Neck Cancer Cohort | Duration of Response | 3.7 Months |
| Non-Small Cell Lung Cancer Cohort | Duration of Response | 7.6 Months |
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Number of Participants With Adverse Events | CTCAE grade 3 or 4 | 23 participants |
| Head and Neck Cancer Cohort | Number of Participants With Adverse Events | CTCAE grade 1 or 2 | 25 participants |
| Non-Small Cell Lung Cancer Cohort | Number of Participants With Adverse Events | CTCAE grade 1 or 2 | 17 participants |
| Non-Small Cell Lung Cancer Cohort | Number of Participants With Adverse Events | CTCAE grade 3 or 4 | 17 participants |
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.
Time frame: Up to 41 months
Population: All enrolled patients are included. Statistical analysis was not performed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Head and Neck Cancer Cohort | Overall Survival (OS) | 8.6 Months |
| Non-Small Cell Lung Cancer Cohort | Overall Survival (OS) | 11.8 Months |
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.
Time frame: Up to 23 months
Population: All patients were included in the analysis. Statistical analysis was not performed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Head and Neck Cancer Cohort | Progression Free Survival (PFS) | 2.6 Months |
| Non-Small Cell Lung Cancer Cohort | Progression Free Survival (PFS) | 3.0 Months |
Other Pre-specified
Association of Biomarkers With Overall Response Rate - EphrinB2 Positive/HPV-negative
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Response Rate - EphrinB2 Positive/HPV-negative | 5 Participants |
Other Pre-specified
Association of Biomarkers With Overall Response Rate - EphrinB2 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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Response Rate - EphrinB2 Status | EphrinB2 Negative who achieved CR/PR | 9 Participants |
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Response Rate - EphrinB2 Status | EphrinB2 Positive who achieved CR/PR | 6 Participants |
p-value: 0.057Fisher Exact
Other Pre-specified
Association of Biomarkers With Overall Response Rate - PD-L1 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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Response Rate - PD-L1 Status | PD-L1 Negative who achieved CR/PR | 3 Participants |
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Response Rate - PD-L1 Status | PD-L1 Positive who achieved CR/PR | 3 Participants |
p-value: 1Fisher Exact
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Survival (OS) - EphrinB2 | EphrinB2 Negative | 7.0 Months |
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Survival (OS) - EphrinB2 | EphrinB2 Positive | 10.9 Months |
p-value: 0.83Log Rank
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Survival (OS) - EphrinB2 Positive/HPV-negative | 10.9 Months |
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Survival (OS) - HPV Status | HPV Negative | 8.6 Months |
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Survival (OS) - HPV Status | HPV Positive | 7.0 Months |
p-value: 0.83Log Rank
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Survival (OS) - P16 Status | P16 Negative | 8.6 Months |
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Survival (OS) - P16 Status | P16 Positive | 7.0 Months |
p-value: 0.83Log Rank
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Survival (OS) - PD-L1 Status | PD-L1 Negative | 12.3 Months |
| Head and Neck Cancer Cohort | Association of Biomarkers With Overall Survival (OS) - PD-L1 Status | PD-L1 Positive | 7.6 Months |
p-value: 0.47Log Rank
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Progression Free Survival (PFS) - EphrinB2 Positive/HPV-negative | 3.2 Months |
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Progression Free Survival (PFS) - EphrinB2 Status | EphrinB2 Negative | 2.5 Months |
| Head and Neck Cancer Cohort | Association of Biomarkers With Progression Free Survival (PFS) - EphrinB2 Status | EphrinB2 Positive | 2.9 Months |
p-value: 0.11Log Rank
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Progression Free Survival (PFS) - HPV Status | HPV Negative | 2.5 Months |
| Head and Neck Cancer Cohort | Association of Biomarkers With Progression Free Survival (PFS) - HPV Status | HPV Positive | 2.6 Months |
p-value: 0.83Log Rank
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Progression Free Survival (PFS) - P16 Status | P16 Negative | 2.5 Months |
| Head and Neck Cancer Cohort | Association of Biomarkers With Progression Free Survival (PFS) - P16 Status | P16 Positive | 2.6 Months |
p-value: 0.83Log Rank
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarkers With Progression Free Survival (PFS) - PD-L1 Status | PD-L1 Negative | 2.8 Months |
| Head and Neck Cancer Cohort | Association of Biomarkers With Progression Free Survival (PFS) - PD-L1 Status | PD-L1 Positive | 2.5 Months |
p-value: 0.96Log Rank
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarker With Overall Response Rate - HPV Status | HPV Negative who achieved CR/PR | 5 Participants |
| Head and Neck Cancer Cohort | Association of Biomarker With Overall Response Rate - HPV Status | HPV Positive who achieved CR/PR | 1 Participants |
p-value: 0.34Fisher Exact
Other Pre-specified
Association of Biomarker With Overall Response Rate - P16 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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Head and Neck Cancer Cohort | Association of Biomarker With Overall Response Rate - P16 Status | P16 Negative who achieved CR/PR | 5 Participants |
| Head and Neck Cancer Cohort | Association of Biomarker With Overall Response Rate - P16 Status | P16 Positive who achieved CR/PR | 1 Participants |
p-value: 0.34Fisher Exact