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ALK Gene MutationPhase 2NCT03049618

Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475

A Phase 2 study testing Laboratory Biomarker Analysis, Pembrolizumab and Recombinant EphB4-HSA Fusion Protein in people with ALK Gene Mutation and BRAF Gene Mutation, run by University of Southern California at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Pembrolizumab and Recombinant EphB4-HSA Fusion Protein
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
10 Mar 2017to 4 Sep 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

Other trials in United States

About this study

Official title: A Phase IIa Trial of sEphB4-HSA in Combination With Anti PD-1 Antibody (Pembrolizumab, MK3475) in Patients With Non-small Cell Lung and Head/Neck Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the response rate of the combination of pembrolizumab and recombinant EphB4-HSA fusion protein (sEphB4-HSA) as combination therapy.

SECONDARY OBJECTIVES:

  1. 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.

Being tested
Laboratory Biomarker Analysis, Pembrolizumab, Recombinant EphB4-HSA Fusion Protein
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

  • Recombinant EphB4-HSA Fusion ProteinBiological

    Also called sEphB4-HSA

    Given IV

Study groups in NCT03049618
Study groupRoleWhat they receive
Head and Neck Cancer CohortExperimentalPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Recombinant EphB4-HSA Fusion Protein
Non-Small Cell Lung Cancer CohortExperimentalPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Recombinant EphB4-HSA Fusion Protein

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 22 months

Secondary outcomes (4)

  1. Duration of Response

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

    Measured: Up to 22 months

  2. 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.

    Measured: 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).

  3. 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.

    Measured: Up to 41 months

  4. 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.

    Measured: Up to 23 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Feb 2017
  2. Study start10 Mar 2017
  3. Primary completion4 Sep 2024
  4. Study completion4 Sep 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03049618
Sponsor's protocol ID
0S-16-8
Other IDs
NCI-2017-00189, 0S-16-8, P30CA014089
Status last verified
Oct 2025
First submitted
8 Feb 2017
Last updated
22 Oct 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis, Pembrolizumab and Recombinant EphB4-HSA Fusion Protein in people with ALK Gene Mutation and BRAF Gene Mutation, run by University of Southern California at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Up to 22 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03049618.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2025.

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