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NSCLC Stage IVPhase 2NCT03411473

Study of AGEN1884 With Pembrolizumab in 1L NSCLC

A Phase 2 study testing AGEN1884 in combination with pembrolizumab in people with NSCLC Stage IV, run by Agenus Inc. at 5 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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 more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
NSCLC Stage IV
What is being tested?
AGEN1884 in combination with pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
5 sitesin 2 countries
Study dates
4 Oct 2017to 1 Mar 2019
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Voluntarily agree to participate.
  • Be ≥18 years of age.
  • Have a histologically 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 metastatic NSCLC.
  • Have measurable disease based on RECIST 1.1 as determined by the site.
  • Have a life expectancy of at least 3 months and a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
  • Have adequate organ function as indicated by the following laboratory values:
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  • Adequate hematological function defined by absolute neutrophil count (ANC) > 1.5 x 109/L, platelet count > 100 x 109/L, and hemoglobin > 9 g/dL (without transfusions within 2 weeks of first dose).
  • Adequate hepatic function based by a total bilirubin level < the institutional upper limit of normal (IULN), aspartate aminotransferase (AST) level < 1.5 x IULN, alanine aminotransferase (ALT) level < 1.5 x IULN, and alkaline phosphatase ≤ 2.5 ULN.
  • Adequate renal function defined as Creatinine ≤ 1.5 x IULN OR calculated creatinine clearance > 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).
  • Adequate coagulation defined by international normalized ratio (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)
  • 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.
  • Subject has no history of prior malignancy, 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.
  • Have provided a formalin fixed tumor tissue sample from a biopsy 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 PD-L1 status.
  • The subject's tumor does not harbor an EGFR sensitizing (activating) mutation or ALK translocation.
  • The subject's tumor must have high PD-L1 expression (TPS ≥50%) as determined by an FDA-approved test.
  • Female subjects must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication) if of childbearing potential or be of non-child bearing potential.
  • 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.
  • 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 contraception is required for the pregnant partner.
  • Subject is willing and able to comply with the requirements of the protocol.

Who cannot join

  • Has an EGFR sensitizing mutation and/or an ALK translocation.
  • Has received systemic therapy for the treatment of their stage IV NSCLC. Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment.
  • Is receiving systemic steroid therapy < 3 days prior to the first dose of trial treatment or receiving any other form of immunosuppressive medication.
  • 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)
  • 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.
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  • Has received prior therapy with an anti-PD-1, 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).
  • 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.
  • Active autoimmune 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.
  • Has had an allogeneic tissue/solid organ transplant.
  • Has interstitial lung disease (ILD) OR has had a history of pneumonitis that has required oral or IV steroids.
  • Has received or will receive a live vaccine within 30 days prior to the first administration of study medication. Seasonal flu vaccines that do not contain a live virus are permitted
  • Has an active infection requiring intravenous systemic therapy.
  • Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B, Hepatitis C or tuberculosis.
  • Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥II), or serious uncontrolled cardiac arrhythmia requiring medication.
  • 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, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
  • 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.

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

Australia4 sites

  • Mater Research

    Brisbane

  • Scientia Clinical Research

    Sydney

  • John Flynn Private Hospital

    Tugun

  • Sydney Adventist

    Wahroonga

Other trials in Australia

New Zealand1 site

  • Auckland City Hospital

    Auckland

Other trials in New Zealand

About this study

Official title: A Phase IIa Open-Label Trial of AGEN1884 in Combination With Pembrolizumab in Subjects With Chemotherapy Naïve, PD-L1 High, Metastatic Non-Small Cell Lung Cancer (NSCLC)

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.

Conditions
NSCLC Stage IV
Being tested
AGEN1884 in combination with pembrolizumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • AGEN1884 in combination with pembrolizumabBiological

    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

Study groups in NCT03411473
Study groupRoleWhat they receive
AGEN1884 with pembrolizumabExperimentalAGEN1884 in combination with pembrolizumab
Receives: Biological: AGEN1884 in combination with pembrolizumab

What is being measured

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

  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

    Measured: 21 days

Secondary outcomes (9)

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

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

    Measured: 116 weeks

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

    Frequency, severity, and duration of treatment-related AEs

    Measured: 116 weeks

  3. Confirmed BOR per RECIST 1.1

    Confirmed BOR per RECIST 1.1

    Measured: 116 weeks

  4. Duration of response per RECIST 1.1

    Duration of response per RECIST 1.1

    Measured: 36 months

  5. PFS time

    PFS time

    Measured: 36 months

  6. OS time

    OS time

    Measured: 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

    Measured: Up to 24 months from 1st dose of treatment

  8. Pharmacokinetic profile of AGEN1884 and pembrolizumab

    Pharmacokinetic profile of AGEN1884 and pembrolizumab

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

  9. Immunogenicity of AGEN1884 and pembrolizumab

    Immunogenicity of AGEN1884 and pembrolizumab

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

Timeline

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

  1. First posted26 Jan 2018
  2. Study start4 Oct 2017
  3. Primary completion1 May 2018
  4. Study completion1 Mar 2019

Why it stopped: Trial will not proceed due to changes in the treatment landscape.

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03411473
Sponsor's protocol ID
C-500-03
Status last verified
May 2020
First submitted
14 Nov 2017
Last updated
2 Jun 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AGEN1884 in combination with pembrolizumab in people with NSCLC Stage IV, run by Agenus Inc. at 5 sites in 2 countries.

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 19 inclusion and 20 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: stopped early, as of the sponsor's last update on 2 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Australia, New Zealand. 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?

The study was stopped early (reason given: Trial will not proceed due to changes in the treatment landscape.). Results are not available in the source record.

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?

Occurrence of DLTs in subjects in the Safety Run-in Phase of the trial (time frame: 21 days). 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 NCT03411473.

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 2 Jun 2020.

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