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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03411473




Registration number
NCT03411473
Ethics application status
Date submitted
14/11/2017
Date registered
26/01/2018
Date last updated
2/06/2020

Titles & IDs
Public title
Study of AGEN1884 With Pembrolizumab in 1L NSCLC
Scientific 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)
Secondary ID [1] 0 0
C-500-03
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
NSCLC Stage IV 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - AGEN1884 in combination with pembrolizumab

Experimental: AGEN1884 with pembrolizumab - AGEN1884 in combination with pembrolizumab


Other interventions: AGEN1884 in combination with 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
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of DLTs in subjects in the Safety Run-in Phase of the trial
Timepoint [1] 0 0
21 days
Secondary outcome [1] 0 0
Frequency, severity, and duration of treatment-emergent AEs (TEAEs)
Timepoint [1] 0 0
116 weeks
Secondary outcome [2] 0 0
Frequency, severity, and duration of treatment-related AEs
Timepoint [2] 0 0
116 weeks
Secondary outcome [3] 0 0
Confirmed BOR per RECIST 1.1
Timepoint [3] 0 0
116 weeks
Secondary outcome [4] 0 0
Duration of response per RECIST 1.1
Timepoint [4] 0 0
36 months
Secondary outcome [5] 0 0
PFS time
Timepoint [5] 0 0
36 months
Secondary outcome [6] 0 0
OS time
Timepoint [6] 0 0
June 2020 ( When 14 patients have completed 2 years of treatment)
Secondary outcome [7] 0 0
Unconfirmed response at 12 weeks from first dose per RECIST 1.1
Timepoint [7] 0 0
Up to 24 months from 1st dose of treatment
Secondary outcome [8] 0 0
Pharmacokinetic profile of AGEN1884 and pembrolizumab
Timepoint [8] 0 0
At least 20 patients have completed 12 weeks from 1st dose of treatment
Secondary outcome [9] 0 0
Immunogenicity of AGEN1884 and pembrolizumab
Timepoint [9] 0 0
All patients on study have completed 6 weeks from 1st dose of treatment

Eligibility
Key inclusion criteria
1. Voluntarily agree to participate.

2. Be =18 years of age.

3. 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.

4. Have measurable disease based on RECIST 1.1 as determined by the site.

5. 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

6. Have adequate organ function as indicated by the following laboratory values:

1. 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).

2. 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.

3. 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).

4. 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)

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 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.

8. 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.

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 childbearing potential 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 contraception is required
for the pregnant partner.

14. Subject is willing and able to comply with the requirements of the protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 neoadjuvant/adjuvant therapy
is allowed as long as therapy was completed at least 6 months prior to the diagnosis
of metastatic disease.

3. 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.

4. Is receiving systemic steroid therapy < 3 days prior to the first dose of trial
treatment or receiving any other form of immunosuppressive 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-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).

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 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.

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 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

13. Has an active infection requiring intravenous systemic therapy.

14. Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

15. Has known active Hepatitis B, Hepatitis C or tuberculosis.

16. 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.

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 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).

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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2019
Sample size
Target
Accrual to date
Final
2
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Mater Research - Brisbane
Recruitment hospital [2] 0 0
Scientia Clinical Research - Sydney
Recruitment hospital [3] 0 0
John Flynn Private Hospital - Tugun
Recruitment hospital [4] 0 0
Sydney Adventist - Wahroonga
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- Sydney
Recruitment postcode(s) [3] 0 0
- Tugun
Recruitment postcode(s) [4] 0 0
- Wahroonga
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Agenus Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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)
Trial website
https://clinicaltrials.gov/ct2/show/NCT03411473
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Agenus Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03411473