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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03495882




Registration number
NCT03495882
Ethics application status
Date submitted
19/01/2018
Date registered
12/04/2018

Titles & IDs
Public title
Subjects With Metastatic or Locally Advanced Solid Tumors, and Expansion Into Select Solid Tumors (Cervical)
Scientific title
A Phase 1 / 2, Open-Label, Multi-Arm Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN1884 in Combination With AGEN2034 in Subjects With Metastatic or Locally Advanced Solid Tumors, and Expansion Into Select Solid Tumors
Secondary ID [1] 0 0
C-550-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cervical Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Cervical (cervix)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AGEN1884 + AGEN2034

Experimental: AGEN1884 + AGEN2034 - AGEN1884 in combination with AGEN2034 in subjects with Subjects with Metastatic or Locally Advanced Solid Tumors, and Expansion into Select Solid Tumors (cervical)


Treatment: Drugs: AGEN1884 + AGEN2034
AGEN1884 + AGEN2034 according to protocol design
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR), as determined by IERC, in the analysis population
Timepoint [1] 0 0
Evaluated throughout the protocol, up to 2 years.
Secondary outcome [1] 0 0
Safety and Tolerability of AGEN2034 and AGEN1884
Timepoint [1] 0 0
From the time of the first dose to the end of follow-up (up to 2 years after the last dose).
Secondary outcome [2] 0 0
Maximum drug concentration observed postdose at steady-state (Cmax-ss)
Timepoint [2] 0 0
Pre-dose through 3 months after last dose.
Secondary outcome [3] 0 0
Minimum observed concentration at steady-state (Cmin-ss)
Timepoint [3] 0 0
Pre-dose through 3 months after last dose.
Secondary outcome [4] 0 0
Area under the drug concentration-time curve within time span t1 to t2 at steady-state (AUC(t1-t2)-ss)
Timepoint [4] 0 0
Pre-dose through 3 months after last dose.
Secondary outcome [5] 0 0
Area under the drug concentration-time curve from time zero to time t (AUC(0-t)), area under the drug concentration-time curve from time zero to infinity (AUC(0-8))
Timepoint [5] 0 0
Pre-dose through 3 months after last dose.
Secondary outcome [6] 0 0
Time to maximum observed concentration (tmax)
Timepoint [6] 0 0
Pre-dose through 3 months after last dose.
Secondary outcome [7] 0 0
Terminal disposition rate constant (?z)
Timepoint [7] 0 0
Pre-dose through 3 months after last dose.
Secondary outcome [8] 0 0
Terminal elimination half-life (t1/2)
Timepoint [8] 0 0
Pre-dose through 3 months after last dose.
Secondary outcome [9] 0 0
Systemic clearance (CL)
Timepoint [9] 0 0
Pre-dose through 3 months after last dose.
Secondary outcome [10] 0 0
Volume of distribution (Vd)
Timepoint [10] 0 0
Pre-dose through 3 months after last dose.
Secondary outcome [11] 0 0
Immunogenicity of AGEN2034 and AGEN1884
Timepoint [11] 0 0
Pre-dose through 3 months after last dose.
Secondary outcome [12] 0 0
Objective Response Rate (ORR), as determined by investigator
Timepoint [12] 0 0
Evaluated throughout the protocol, up to 2 years.
Secondary outcome [13] 0 0
Duration of Response (DOR)
Timepoint [13] 0 0
Time from first observation of response to first observation of documented disease progression, up to 3 years.
Secondary outcome [14] 0 0
Disease Control Rate (DCR)
Timepoint [14] 0 0
Duration of the trial, up to 3 years.
Secondary outcome [15] 0 0
Duration of Stable Disease (SD)
Timepoint [15] 0 0
Duration of the trial, up to 3 years.
Secondary outcome [16] 0 0
Time to Response
Timepoint [16] 0 0
Duration of the treatment phase of the trial, up to 2 years.
Secondary outcome [17] 0 0
Progression-free Survival (PFS)
Timepoint [17] 0 0
Duration of the treatment phase of the trial, up to 2 years.
Secondary outcome [18] 0 0
Overall Survival Rate (OS)
Timepoint [18] 0 0
Duration of the treatment phase of the trial, up to 2 years.

Eligibility
Key inclusion criteria
To be eligible for participation in this trial the subject must:

1. Voluntarily agree to participate by giving written informed consent. (Participation in pharmacogenomics testing is optional.)
2. Be =18 years of age.
3. Diagnosis:

1. Phase 1: Male or female having a histologically or cytologically confirmed diagnosis of a locally advanced, recurrent, and/or metastatic solid tumor for which no standard therapy is available or standard therapy has failed.
2. Phase 2:

I. Female having (1) a histologically or cytologically confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, and (2) locally advanced, recurrent, and/or metastatic disease at the time of enrollment. Histologic confirmation of the original primary tumor is required via pathology report.

Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric type adenocarcinoma, clear cell carcinoma, and mesonephric carcinoma.

II. Has cervical cancer and has relapsed after a platinum-based treatment (first line) regimen for locally advanced, recurrent, and/or metastatic disease; Note: Subjects who only received platinum-based chemotherapy concurrently with primary radiation (e.g., weekly cisplatin) or adjuvant chemotherapy following completion of radiation therapy (e.g., paclitaxel and carboplatin for =4 cycles) and progressed within 6 months after treatment completion will be eligible as this systemic therapy will be considered first line.
4. Measurable Disease:

1. Phase 1: Have objective evidence of disease; the presence of measurable disease is not required.
2. Phase 2: Have measurable disease on imaging based on RECIST version 1.1. Note: Subjects must have at least one "target lesion" to be used to assess response, as defined by RECIST version 1.1. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented, or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.

Note: Measurable disease by RECIST 1.1 must be confirmed by independent central radiologic review prior to first dose. Subjects without centrally confirmed measurable disease at baseline will not be eligible for this trial.
5. Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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 10^9/L, platelet count =100 x 10^9/L, and hemoglobin

=8 g/dL (without transfusions within 1 week of first dose).
2. Adequate hepatic function based on a total bilirubin level <1.5 x the institutional upper limit of normal (IULN), aspartate aminotransferase (AST) level =2.5 x IULN, alanine aminotransferase (ALT) level =2.5 x IULN, and alkaline phosphatase =2.5 IULN.
3. Adequate renal function defined as creatinine =1.5 x IULN OR calculated creatinine clearance =50 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)
7. Other than the cancer for which the subject is enrolled, have no history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous-cell carcinoma of the skin, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.

Note: In Phase 2, the history and time requirement for no evidence of disease for 5 years does not apply to the cancer for which the subject is enrolled in the trial.
8. In Phase 2, subjects must provide a sufficient and adequate formalin fixed paraffin embedded (FFPE) tumor tissue sample preferably from the most recent biopsy of a tumor lesion, collected either at the time of or after the diagnosis of locally advanced, recurrent, and/or metastatic disease has been made AND from a site not previously irradiated. If no tumor tissue is available, a fresh biopsy will be required.

Note: Tissue from needle or excisional biopsy or from resection is required.
9. Female subjects must have a negative serum pregnancy test at screening (within 72 hours of first dose of study drug) if of childbearing potential or be of non- childbearing potential. Non-childbearing potential is defined as (by other than medical reasons):

1. =45 years of age and has not had menses for greater than 1 year,
2. Amenorrheic for = 2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone (FSH) value in the postmenopausal range upon pretrial (screening) evaluation,
3. Whose status is post hysterectomy, oophorectomy, or tubal ligation.
10. If of childbearing potential, female subjects must be willing to use 2 highly effective contraceptive measures (defined in the informed consent form [ICF]) throughout the study, starting with the screening visit through 120 days after the last dose of study drug.

Note: Abstinence is acceptable if this is the established and preferred contraception for the subject.
11. Male subjects with a female partner(s) of childbearing potential must agree to use 2 highly effective contraceptive measures (defined in the ICF) throughout the trial starting with the screening visit through 120 days after the last dose of study drug is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

Note: Abstinence is acceptable if this is the established and preferred contraception for the subject.
12. Is willing and able to comply with the requirements of the protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

The subject must be excluded from participating in the trial if the subject:

1. Is currently participating and receiving trial 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.
2. Has an inadequate washout period prior to first dose of study drug defined as:

1. Received systemic cytotoxic chemotherapy or biological therapy within 3 weeks before first dose,
2. Received radiation therapy within 3 weeks before first dose, or
3. Had major surgery within 4 weeks before first dose.
3. Has received prior therapy with:

1. Any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies
2. For Phase 2: >1 systemic treatment regimen for the locally advanced recurrent, and/or metastatic cervical cancer for which the subject is considered for the study. Subjects who received a systemic regimen immediately after progressing within 6 months of completing chemotherapy concurrent with primary radiation or adjuvant chemotherapy after radiation will only be considered as having 1 prior systemic regimen for the purpose of this criterion.

Note: In Phase 1, prior treatment with a CTLA-4 antibody is permissible for subjects with metastatic melanoma.
4. Has persisting toxicity related to prior therapy of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE) Grade >1 severity.

Note: Sensory neuropathy or alopecia of Grade =2 is acceptable.
5. Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent, radiation therapy, and/or surgical resection).
6. Has known severe hypersensitivity reactions to fully human monoclonal antibodies (NCI-CTCAE Version 4.03 Grade =3), any history of anaphylaxis, or uncontrolled asthma.
7. Is receiving systemic corticosteroid therapy =7 days prior to first dose of study treatment or receiving any other form of systemic immunosuppressive medication (corticosteroid use on study for management of immune-related adverse events (AE), and/or a premedication for intravenous (IV) contrast allergies/reactions is allowed). Subjects who are receiving daily corticosteroid replacement therapy are an exception to this rule. Examples of permitted therapy are daily prednisone at doses of 5 to 7.5 mg or equivalent hydrocortisone dose, and steroid therapy administered by topical, intraocular, intranasal, and/or inhalation routes.
8. Has a central nervous system (CNS) tumor, metastasis(es), and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period OR identified prior to consent.

Note: Subjects with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions at screening (based on 2 sets of brain images performed =4 weeks apart, and obtained after the brain metastases treatment). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be minimal and be expected as sequelae from treated lesions. For individuals who received steroids as part of brain metastases treatment, steroids must be discontinued =7 days prior to first dose of study drug.
9. Has active or history of autoimmune disease that has required systemic treatment within 2 years of the start of study treatment (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 immunosuppressive systemic treatment.

Note: Subjects with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
10. Has had an allogeneic tissue/solid organ transplant.
11. Has or had interstitial lung disease (ILD) OR has had a history of pneumonitis that has required oral or IV corticosteroids.
12. Has an active infection requiring IV systemic therapy.
13. Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
14. Has known active Hepatitis B, Hepatitis C, or tuberculosis. Active Hepatitis B is defined as a known positive HBsAg result. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay.
15. 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.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
18. 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).
19. Is legally incapacitated or has limited legal capacity.
20. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of AGEN2034 and/or AGEN1884.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/12/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/07/2022
Sample size
Target
Accrual to date
Final
154
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Linear Clinical Research - Perth
Recruitment hospital [2] 0 0
Mater Research - South Brisbane
Recruitment hospital [3] 0 0
Icon Cancer Care South Brisbane - South Brisbane
Recruitment hospital [4] 0 0
Scientia Clinical Research - Sydney
Recruitment postcode(s) [1] 0 0
6009 - Perth
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
- South Brisbane
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Oklahoma
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Brazil
State/province [12] 0 0
São Paulo
Country [13] 0 0
Georgia
State/province [13] 0 0
Tbilisi
Country [14] 0 0
Hungary
State/province [14] 0 0
Budapest
Country [15] 0 0
Hungary
State/province [15] 0 0
Debrecen
Country [16] 0 0
Hungary
State/province [16] 0 0
Kecskemét
Country [17] 0 0
Hungary
State/province [17] 0 0
Pécs
Country [18] 0 0
Hungary
State/province [18] 0 0
Szeged
Country [19] 0 0
Hungary
State/province [19] 0 0
Szolnok
Country [20] 0 0
Hungary
State/province [20] 0 0
Zalaegerszeg
Country [21] 0 0
Moldova, Republic of
State/province [21] 0 0
Chisinau
Country [22] 0 0
Poland
State/province [22] 0 0
Nadarzyn
Country [23] 0 0
Poland
State/province [23] 0 0
Warszawa
Country [24] 0 0
Spain
State/province [24] 0 0
L'Hospitalet De Llobregat
Country [25] 0 0
Spain
State/province [25] 0 0
Madrid
Country [26] 0 0
Spain
State/province [26] 0 0
Pamplona
Country [27] 0 0
Spain
State/province [27] 0 0
Sevilla
Country [28] 0 0
Spain
State/province [28] 0 0
Valencia
Country [29] 0 0
Ukraine
State/province [29] 0 0
Dnipro
Country [30] 0 0
Ukraine
State/province [30] 0 0
Ivano-Frankivs'k
Country [31] 0 0
Ukraine
State/province [31] 0 0
Kharkiv
Country [32] 0 0
Ukraine
State/province [32] 0 0
Khmelnytskyi
Country [33] 0 0
Ukraine
State/province [33] 0 0
Kiev
Country [34] 0 0
Ukraine
State/province [34] 0 0
Kyiv
Country [35] 0 0
Ukraine
State/province [35] 0 0
Luts'k

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03495882