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Subjects With Metastatic or Locally Advanced Solid Tumors, and Expansion Into Select Solid Tumors (Cervical)

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ClinicalTrials.gov Identifier: NCT03495882
Recruitment Status : Recruiting
First Posted : April 12, 2018
Last Update Posted : July 24, 2018
Sponsor:
Information provided by (Responsible Party):
Agenus Inc.

Brief Summary:
This is a Phase 1/2, open-label, multi-arm study, of AGEN1884 in combination with AGEN2034 in subjects with advanced solid tumors including cervical cancer.

Condition or disease Intervention/treatment Phase
Cervical Cancer Drug: AGEN1884 + AGEN2034 Phase 1 Phase 2

Detailed Description:

This is a Phase 1/2, open-label, multi-arm study, of AGEN1884 in combination with AGEN2034 in subjects with advanced solid tumors including cervical cancer. AGEN2034 is a novel, fully human monoclonal immunoglobulin G4 (IgG4) antibody, designed to block program cell death-1 (PD-1). AGEN1884 is a novel, fully human monoclonal immunoglobulin G1 (IgG1) antibody, designed to block cytotoxic T lymphocyte antigen-4 (CTLA-4).

The study consists of two phases:

  • Phase 1: Dose escalation
  • Phase 2: Expansion in Select Tumors - CERVICAL

Phase 1: Part A - Dose Escalation:

The study will consist initially of a 3+3 dose escalation that will evaluate different combination dose levels of AGEN1884 and AGEN2034 in subjects with advanced / refractory solid tumors.

Phase 2: Expansion in Select Tumors

To further characterize safety and efficacy, the following expansion cohort will be enrolled:

Part B - recurrent, unresectable, or metastatic cervical cancer In Phase 2, the selected CDL of AGEN2034 and AGEN1884, established in Part A, will be administered for a maximum of 2 years or until confirmed progression, unacceptable toxicity, or any criterion for stopping the study drugs or withdrawal from the trial occurs.

For the Phase 2 portion of the study, an Independent Data Management Committee (IDMC) will be established to evaluate safety and efficacy and an Independent Endpoint Review Committee (IERC) will be established to adjudicate tumor response.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 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 (Cervical)
Actual Study Start Date : December 18, 2017
Estimated Primary Completion Date : March 4, 2022
Estimated Study Completion Date : March 4, 2023

Arm Intervention/treatment
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)
Drug: AGEN1884 + AGEN2034
AGEN1884 + AGEN2034 according to protocol design




Primary Outcome Measures :
  1. Assess the safety and tolerability of AGEN1884 in combination with AGEN2034 [ Time Frame: From time of time of first dose until the end of follow-up (up to approximately 60 Weeks). ] ]
    Percentage of participants experiencing any unfavorable and unintended sign, symptom, disease, or worsening of pre-existing condition temporally associated with study therapy and irrespective of causality to study therapy.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) per RECIST 1.1 [ Time Frame: Up to approximately 2 years ]
    ORR is the proportion of the participants who achieve complete response (CR) or partial response (PR) per RECIST 1.1 by Blinded independent central review (BICR)

  2. Duration Of Response (DOR) [ Time Frame: Up to approximately 2 years ]
    DOR is the time from first documented evidence of CR or PR per RECIST 1.1 by Blinded independent central review (BICR) until disease progression per RECIST 1.1 by BICR or death



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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 - Part A: complete
    2. Phase 2 - Part B: Have a histologically or cytologically confirmed diagnosis of metastatic or locally advanced, unresectable squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix; and have relapsed after a platinum-containing doublet administered for treatment of advanced (recurrent, unresectable, or metastatic) disease.
  4. Measurable Disease

    1. Phase 1 - Part A: Complete
    2. Phase 2 - Part B: Have measurable disease on imaging based on RECIST version 1.1.
  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 109/L, platelet count > 100 x 109/L, and hemoglobin > 9 g/dL (without transfusions within 1 week of first dose).
    2. Adequate hepatic function based by a total bilirubin level < 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 > 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)
  7. 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, 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.

    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 study.

  8. In Phase 2, subjects must have provided sufficient and adequate formalin fixed tumor tissue sample preferably from a biopsy of a tumor lesion either at the time of or after the diagnosis of advanced or metastatic disease has been made AND from a site not previously irradiated.
  9. 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. 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 two adequate barrier methods throughout the study, starting with the screening visit through 120 days after the last dose of study treatment.
  11. 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 study treatment is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
  12. Is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

  1. 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.
  2. Has received prior systemic cytotoxic chemotherapy, biological therapy, radiation therapy, OR major surgery within 3 weeks or 5 half-lives (whichever is longer) of the first dose of trial treatment.
  3. Has received prior therapy with 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.
  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.
  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 monoclonal antibodies (NCI-CTCAE Grade ≥3), any history of anaphylaxis, or uncontrolled asthma (i.e., ≥3 features of partly controlled asthma).
  7. Is receiving systemic corticosteroid therapy ≤ 3 days prior to the first dose of trial treatment or receiving any other form of systemic immunosuppressive medication (corticosteroid use on study for management of immune-related adverse events, and/or a premedication for IV contrast allergies/reactions is allowed). Subjects who are receiving daily corticosteroid replacement therapy are an exception to this rule. Daily prednisone at doses of 5-7.5 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy.
  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.
  9. Has active or history of autoimmune disease that has required systemic treatment within 2 years of the start of trial 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 systemic treatment.
  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 intravenous 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 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.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03495882


Contacts
Contact: Sara Coulter 781.674.4480 sara.coulter@agenusbio.com

Locations
Australia
Linear Clinical Research Recruiting
Perth, Australia
Contact: Tarek Meniawy       tarek.meniawy@health.wa.gov.au   
Contact    1300 546 327      
Icon Cancer Care South Brisbane Recruiting
South Brisbane, Australia
Contact: Mr Adam Stoneley    +61 7 3737 4558    adam.stoneley@iconcf.org.au   
Mater Research Recruiting
South Brisbane, Australia
Contact: Catherine Shannon, MD       catherine.shannon@mater.org.au   
Contact    +61 7 3163 7689      
Scientia Clinical Research Recruiting
Sydney, Australia
Contact: James Kuo, MD    +61 2 9382 5800    james.kuo@scientiaclinicalresearch.com.au   
Sponsors and Collaborators
Agenus Inc.
Investigators
Principal Investigator: Dr Jermaine Coward, MD Icon Cancer Care South Brisbane

Responsible Party: Agenus Inc.
ClinicalTrials.gov Identifier: NCT03495882     History of Changes
Other Study ID Numbers: C-550-01
First Posted: April 12, 2018    Key Record Dates
Last Update Posted: July 24, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female