ClinicalTrials.gg
TerminatedNCT03411473Updated Jun 2, 2020

Study of AGEN1884 With Pembrolizumab in 1L NSCLC

A Phase 2 interventional study of AGEN1884 in combination with pembrolizumab in NSCLC Stage IV, sponsored by Agenus Inc.. Terminated at 5 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-06-02.

Sponsored by Agenus Inc. · Phase 2, Interventional, and Treatment

Why this study was terminated
Trial will not proceed due to changes in the treatment landscape.

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Phase
Phase 2
Study type
Interventional
Enrollment
2
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Where this study stands

Counted across the records on this site · 2026-11-14

Among 127 studies testing pembrolizumab in Carcinoma, Non-Small-Cell Lung — 29 open to participants now, 48 under way, 13 of them phase 3. pembrolizumab · Carcinoma, Non-Small-Cell Lung.

Enrollment
124th of 127
2 · median 65
Started
2017
with 14 others
Phase 2
65 of 127
20 open now
Registered
47th of 127
by date

Among the 127 studies testing pembrolizumab in Carcinoma, Non-Small-Cell Lung, this one is the 124th largest by enrollment, is one of 15 that started in 2017, is one of 65 in phase 2, and was the 47th registered.

Carcinoma, Non-Small-Cell Lung

7,621 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,837 are open to participants now.

Browse Carcinoma, Non-Small-Cell Lung studies →

Open to participants now

29 of the 127 studies testing pembrolizumab in Carcinoma, Non-Small-Cell Lung are open now, in 10 countries. Recruiting first, the newest first:

24 more — sign in →

By country, each count listing its studies:

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About pembrolizumab

pembrolizumab: first FDA approval 2014 (KEYTRUDA), first EMA approval 2015. What it is approved for, and how studies give it, is on its page →

Who these studies take

Of the 1,326 Carcinoma, Non-Small-Cell Lung studies recruiting now, 988 (75%) set no upper age limit and 225 (17%) stop at 75 or younger; 34 take children under 18; 40 take healthy volunteers.

This study: 18 Years and older · all sexes · no healthy volunteers.

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02

Study summary

A Phase IIa Open-Label Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN1884 in Combination with Pembrolizumab in Subjects with Chemotherapy Naïve, PD-L1 high, metastatic Non-Small Cell Lung Cancer (NSCLC)

Read the detailed description

This is a Phase IIa, open-label study, of AGEN1884 in combination with pembrolizumab in subjects with stage IV NSCLC whose tumors have high PD-L1 expression and no EGFR or ALK genomic tumor aberrations.

The study consists in two phases:

  • Safety Run-in Phase
  • Efficacy Phase

Subjects will be enrolled in a "3+3" Safety Run-in followed by enrollment completing the efficacy cohort. Two different dose levels of AGEN1884 may be tested in combination with the approved pembrolizumab treatment for this indication (until disease progression, unacceptable toxicity, or up to a maximum of 24 months). Each subject will stay on the dose level assigned at trial entry.

03

Conditions studied

  • NSCLC Stage IV
04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Voluntarily agree to participate.
  2. Be ≥18 years of age.
  3. Have a or cytologically confirmed diagnosis of NSCLC, is stage IV, does not have an EGFR sensitizing (activating) mutation or ALK translocation, and has not received prior systemic chemotherapy treatment for their NSCLC.
  4. Have based on 1.1 as determined by the site.
  5. Have a of at least 3 months and a performance status of 0 or 1 on the (ECOG) Performance Status
  6. Have adequate organ function as indicated by the following laboratory values:

    1. Adequate hematological function defined by (ANC) > 1.5 x 109/L, count > 100 x 109/L, and > 9 g/dL (without transfusions within 2 weeks of first dose).
    2. Adequate hepatic function based by a total level \< the institutional (IULN), (AST) level \< 1.5 x IULN, alanine aminotransferase (ALT) level \< 1.5 x IULN, and alkaline phosphatase ≤ 2.5 ULN.
    3. Adequate renal function defined as Creatinine ≤ 1.5 x IULN OR calculated > 60 mL/min for subjects with creatinine levels > 1.5 x IULN (If no local guideline is available, creatinine clearance should be calculated using the Cockcroft-Gault Method).
    4. Adequate coagulation defined by (INR) or prothrombin time ≤ 1.5 x IULN (unless the subject is receiving anticoagulant therapy); and activated partial thromboplastin time (aPTT) ≤ 1.5 x IULN (unless the subject is receiving anticoagulant therapy)
    5. Adequate endocrine function defined by thyroid stimulating hormone (TSH) within normal limits. Note: if TSH is not within normal limits at baseline, the subject may still be eligible if T3 and free T4 are within normal limits.
  7. Subject has no history of prior , with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
  8. Have provided a formalin fixed tumor tissue sample from a of a tumor lesion either at the time of or after the diagnosis of metastatic disease has been made AND from a site not previously irradiated to assess for status.
  9. The subject's tumor does not harbor an EGFR sensitizing (activating) mutation or ALK translocation.
  10. The subject's tumor must have high PD-L1 expression (TPS ≥50%) as determined by an FDA-approved test.
  11. Female subjects must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication) if of or be of non-child bearing potential.
  12. If of childbearing potential, female subjects must be willing to use two adequate barrier methods throughout the study, starting with the screening visit through 120 days after the last dose of study therapy.
  13. Male subjects with a female partner(s) of child-bearing potential must agree to use two adequate barrier methods throughout the trial starting with the screening visit through 120 days after the last dose of pembrolizumab is received. Males with pregnant partners must agree to use a condom; no additional method of is required for the pregnant partner.
  14. Subject is willing and able to comply with the requirements of the protocol.

Exclusion criteria

Exclusion Criteria:

  1. Has an EGFR sensitizing mutation and/or an ALK translocation.
  2. Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of treatment with chemotherapy and/or radiation as part of /adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of disease.
  3. Is currently participating and receiving study therapy or has participated in a study of an agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment.
  4. Is receiving systemic therapy \< 3 days prior to the first dose of trial treatment or receiving any other form of medication.
  5. Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent for NSCLC, radiation therapy, and/or surgical resection)
  6. Has received prior systemic cytotoxic chemotherapy, biological therapy, OR major surgery within 3 weeks of the first dose of trial treatment; received thoracic radiation therapy of > 30 Gy within 6 months of the first dose of trial treatment.
  7. Has received prior therapy with an , anti-PD-L1, anti-PD-L2, anti-CD137, 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).
  8. Has central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period OR identified prior to signing the ICF.
  9. Active disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  10. Has had an allogeneic tissue/solid organ transplant.
  11. Has interstitial lung disease (ILD) OR has had a history of pneumonitis that has required oral or IV steroids.
  12. Has received or will receive a within 30 days prior to the first administration of study medication. Seasonal flu vaccines that do not contain a live virus are permitted
  13. Has an active infection requiring intravenous systemic therapy.
  14. Has known history of (HIV) (HIV 1/2 antibodies).
  15. Has known active , or tuberculosis.
  16. Has (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure ( class ≥II), or serious uncontrolled cardiac arrhythmia requiring medication.
  17. 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.
  18. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  19. Is, at the time of signing , a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
  20. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit (Visit 1) through 120 days after the last dose of pembrolizumab or AGEN1884.
Terms in these criteria, in plain language(31)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Measurable disease

The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.

The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.

RECIST

The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.

“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

INR, PT and aPTT (clotting tests)

Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.

Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

PD-1, PD-L1 and checkpoint inhibitors

PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.

PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Adjuvant and neoadjuvant

Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

Live vaccines

Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
2 participants (actual)

Study arms

  • Experimental
    AGEN1884 with pembrolizumab

    AGEN1884 in combination with pembrolizumab

    Biological: AGEN1884 in combination with pembrolizumab

Interventions

  • BiologicalAGEN1884 in combination with pembrolizumab

    Drug pages: Zalifrelimab · Pembrolizumab

    AGEN1884 in combination with pembrolizumab in subjects with stage IV NSCLC whose tumors have high PD-L1 expression and no EGFR or ALK genomic tumor aberrations

06

What researchers measure

Primary outcomes

  1. Occurrence of DLTs in subjects in the Safety Run-in Phase of the trial

    Occurrence of DLTs in subjects in the Safety Run-in Phase of the trial

    Time frame: 21 days

Secondary outcomes

  1. Frequency, severity, and duration of treatment-emergent AEs (TEAEs)

    Frequency, severity, and duration of treatment-emergent AEs (TEAEs)

    Time frame: 116 weeks

  2. Frequency, severity, and duration of treatment-related AEs

    Frequency, severity, and duration of treatment-related AEs

    Time frame: 116 weeks

  3. Confirmed BOR per RECIST 1.1

    Confirmed BOR per RECIST 1.1

    Time frame: 116 weeks

  4. Duration of response per RECIST 1.1

    Duration of response per RECIST 1.1

    Time frame: 36 months

  5. PFS time

    PFS time

    Time frame: 36 months

  6. OS time

    OS time

    Time frame: June 2020 ( When 14 patients have completed 2 years of treatment)

  7. Unconfirmed response at 12 weeks from first dose per RECIST 1.1

    Unconfirmed response at 12 weeks from first dose per RECIST 1.1

    Time frame: Up to 24 months from 1st dose of treatment

  8. Pharmacokinetic profile of AGEN1884 and pembrolizumab

    Pharmacokinetic profile of AGEN1884 and pembrolizumab

    Time frame: At least 20 patients have completed 12 weeks from 1st dose of treatment

  9. Immunogenicity of AGEN1884 and pembrolizumab

    Immunogenicity of AGEN1884 and pembrolizumab

    Time frame: All patients on study have completed 6 weeks from 1st dose of treatment

07

Study locations

5 sites
  • Mater Research
    Brisbane, Australia
  • Scientia Clinical Research
    Sydney, Australia
  • John Flynn Private Hospital
    Tugun, Australia
  • Sydney Adventist
    Wahroonga, Australia
  • Auckland City Hospital
    Auckland, New Zealand
08

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Oct 2017 to primary completion in May 2018, 6 months.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 14, 2017
First posted
Jan 26, 2018
StartActual
Oct 4, 2017
Primary completionActual
May 1, 2018
CompletionActual
Mar 1, 2019
Last update
Jun 2, 2020
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jun 2, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03411473
Lead sponsor
Agenus Inc.
Responsible party
Sponsor
First posted
Jan 26, 2018
Start date
Oct 4, 2017
Primary completion
May 1, 2018
Completion
Mar 1, 2019
Last update
Jun 2, 2020

Study contacts

Medical Director
study director · Agenus Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in May 2020. You cannot join it, but the record below documents what was studied.

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Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Zalifrelimab · Pembrolizumab

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