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A Study in Subjects With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04156100
Recruitment Status : Recruiting
First Posted : November 7, 2019
Last Update Posted : June 1, 2020
Sponsor:
Information provided by (Responsible Party):
Agenus Inc.

Brief Summary:
This study is an open-label, Phase 1 study to evaluate the safety, tolerability, PK, and pharmacodynamic profiles of AGEN1223 and to assess the maximum tolerated dose (MTD) in subjects with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: AGEN1223 Phase 1

Detailed Description:
This study is an open-label, Phase 1 study to evaluate the safety, tolerability, PK, and pharmacodynamic profiles of AGEN1223 and to assess the maximum tolerated dose (MTD) in subjects with advanced solid tumors. This monotherapy study will also determine the RP2D of the monotherapy. This Phase 1 study will be conducted in an accelerated titration (for the first two dosing cohorts) and standard 3+3 dose escalation format. AGEN1223 will be administered on Day 1 of each 3-week cycle for 2 years or until any progressive disease (PD) or unacceptable toxicity is reported. The safe starting dose will be at the estimated minimally anticipated biological effect level (MABEL). The treatment phase is divided into 3-week cycles with associated evaluations and procedures that must be performed at specific timepoints. Tumor assessments will be conducted every 6 weeks (±3 days) from first dose until treatment discontinuation. Each cycle begins with the administration of AGEN1223 on Day 1 of a 3-week cycle (timing of doses may be adjusted for management of adverse events [AEs]). Subjects will be treated for up to 2 years or until PD or unacceptable toxicity occurs. A Safety Monitoring Committee (SMC) will be established to assess safety and decide on dose escalation

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of AGEN1223, a Bispecific Antibody in Subjects With Advanced Solid Tumors
Actual Study Start Date : December 10, 2019
Estimated Primary Completion Date : February 14, 2023
Estimated Study Completion Date : February 14, 2024

Arm Intervention/treatment
Experimental: AGEN1223 Drug: AGEN1223
AGEN1223 is a bispecific antibody.




Primary Outcome Measures :
  1. Dose Limiting Toxicity (DLT) [ Time Frame: First 28 days of treatment ]
    In subjects in dose escalation


Secondary Outcome Measures :
  1. Frequency, severity, and duration of treatment-emergent AEs (TEAEs) [ Time Frame: Screening through 90 days after last dose ]
    For all dose groups according to NCI-CTCAE Version 5.0

  2. Maximum observed concentration at steady state (Cmax-ss) [ Time Frame: From first dose through 1 year of treatment ]
    PK Profile of AGEN1223

  3. Minimum observed concentration at steady state (Cmin-ss) [ Time Frame: From first dose through 1 year of treatment ]
    PK Profile of AGEN1223

  4. area under the plasma/serum concentration-time curve within time span t1 to t2 at steady-state (AUC(t1-t2)-ss) [ Time Frame: From first dose through 1 year of treatment ]
    PK Profile of AGEN1223

  5. area under the plasma/serum concentration-time curve from time zero to time t (AUC(0-t)) [ Time Frame: From first dose through 1 year of treatment ]
    PK Profile of AGEN1223

  6. area under the plasma/serum concentration-time curve from time zero to infinity (AUC(0-∞)) [ Time Frame: From first dose through 1 year of treatment ]
    PK Profile of AGEN1223

  7. time to maximum observed concentration (tmax) [ Time Frame: From first dose through 1 year of treatment ]
    PK Profile of AGEN1223

  8. terminal disposition rate constant (λz) [ Time Frame: From first dose through 1 year of treatment ]
    PK Profile of AGEN1223

  9. terminal elimination half-life (t1/2) [ Time Frame: From first dose through 1 year of treatment ]
    PK Profile of AGEN1223

  10. systemic clearance (CL) [ Time Frame: From first dose through 1 year of treatment ]
    PK Profile of AGEN1223

  11. volume of distribution (Vd). [ Time Frame: From first dose through 1 year of treatment ]
    PK Profile of AGEN1223

  12. Immunogenicity of AGEN1223 [ Time Frame: From first dose through 1 year of treatment ]
  13. Overall Response Rate [ Time Frame: Screening up to 2 years of treatment ]
    Per RECIST 1.1 based on Investigator assessment

  14. Duration of Response [ Time Frame: Screening up to 2 years of treatment ]
    Per RECIST 1.1 based on Investigator assessment

  15. Disease Control Rate [ Time Frame: Screening up to 2 years of treatment ]
    Including complete and partial responders and stable disease (SD) for at least 12 weeks, per RECIST 1.1 based on Investigator assessment.

  16. Progression-free Survival median and/or rate [ Time Frame: Screening up to 2 years of treatment ]
    As defined in the Statistical Analysis Plan


Other Outcome Measures:
  1. PK parameter correlation to pharmacodynamic assessments [ Time Frame: Screening up to 1 year of treatment ]
    immune cell subpopulations in blood)

  2. Characterization of genetic polymorphism of FcyR [ Time Frame: Screening up to 2 years of treatment ]
    In subjects treated with AGEN1223

  3. Biomarkers in tumor tissue and blood [ Time Frame: Screening up to 1 year of treatment ]
    Correlation with tumor responses to AGEN1223 treatment

  4. Median and/or rate of Overall Survival [ Time Frame: Up to 12 months after last dose ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 genetic testing is optional)
  2. Greater than or equal to 18 years of age
  3. Histologically or cytologically confirmed diagnosis of an advanced solid tumor for which no standard therapy is available or standard therapy has failed.
  4. Measurable disease on baseline imaging based on RECIST 1.1.
  5. Life expectancy of at least 3 months and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. Adequate organ function as indicated by the following laboratory values:

    • Adequate hematological function, defined as absolute neutrophil count (ANC) ≥1500/μL, platelet count ≥100,000/μL, and hemoglobin ≥8 g/dL without recent transfusion (defined as a transfusion that has occurred within 2 weeks of the hemoglobin measurement).
    • Adequate hepatic function based by a total bilirubin level ≤1.5 × the institutional upper limit of normal (IULN), aspartate aminotransferase (AST) level ≤2.5 × IULN, alanine aminotransferase (ALT) level ≤2.5 × IULN.
    • Adequate renal function defined as creatinine ≤1.5 × IULN OR measured or calculated creatinine clearance >40 ml/min per institutional standard. Assessment methods should be recorded.
    • Adequate coagulation defined by international normalized ratio (INR) or prothrombin time ≤1.5 × IULN and activated partial thromboplastin time (aPTT) ≤1.5 × IULN (unless the subject is receiving anticoagulant therapy)
  7. No history of prior or concomitant malignancy, with the exception of resected basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, and in situ cervical cancer or other malignancies that have undergone potentially curative therapy with no evidence of disease recurrence for 5 years since initiation of that therapy.

8 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 advanced 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.

9. Female subjects of child-bearing potential must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication). Non-childbearing potential is defined as:

  • ≥45 years of age and has not had menses for greater than 1 year,
  • Amenorrheic for ≥2 years without a hysterectomy and oophorectomy and a folliclestimulating hormone (FSH) value in the postmenopausal range upon pretrial (screening) evaluation,
  • Whose status is post hysterectomy, oophorectomy, or tubal ligation. 10. Female subjects of child-bearing potential must be willing to use highly effective contraceptive measures starting with the screening visit through 120 days after the last dose of study treatment.

Note: Abstinence is acceptable if this is the established and preferred contraception for the subject.

11. Male subjects with a female partner(s) of child-bearing potential must agree to use highly effective contraceptive measures 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.

Note: Abstinence is acceptable if this is the established and preferred contraception method for the subject.

12. Willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

  1. 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 3 weeks of the first dose of current study drug.
  2. Prior therapy with any monoclonal antibody (mAb) or agent binding the same targets as AGEN1223.
  3. Systemic cytotoxic chemotherapy, biological therapy, or major surgery within 3 weeks prior to first dose of study drug; a 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with Sponsor approval.
  4. Persisting toxicity with Grade >1 severity related to prior therapy based on National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE).

    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. Known severe hypersensitivity reactions (NCI-CTCAE Grade ≥3) to fully human mAbs or severe reaction to immuno-oncology agents, such as colitis or pneumonitis, requiring treatment with steroids, or has a history of interstitial lung disease (ILD), any history of anaphylaxis, or uncontrolled asthma.
  7. Systemic corticosteroid therapy 1 week prior to the first dose of study drug or receiving any other form of systemic immunosuppressive medication (corticosteroid use as a premedication for intravenous (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 up to 7.5 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy.
  8. 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 (defined as 2 brain images, both of which are obtained after treatment to the brain metastases. These imaging scans should both be obtained ≥4 weeks apart). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have returned to baseline or resolved. Any steroids administered as part of this therapy must be completed ≥3 days prior to the first dose of study medication.

  9. 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).

    Note: Subjects with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid disease not requiring immunosuppressive treatment are eligible.

  10. Allogeneic tissue/solid organ transplant.
  11. ILD OR has had a history of pneumonitis that has required oral or IV corticosteroids.
  12. Active infection requiring treatment.
  13. History of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
  14. Active hepatitis B and/or hepatitis C virus (HBV and HCV).
  15. 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. 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. Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  18. Legally incapacitated or has limited legal capacity.
  19. Pregnant or breastfeeding.

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): NCT04156100


Contacts
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Contact: Agenus, Inc. Clinical Trial Information 781-674-4265 clinicaltrialinfo@Agenusbio.com

Locations
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United States, Arizona
Honor Health Research Institute Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Michael Gordon, MD         
Principal Investigator: Michael Gordon, MD         
United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Anthony El-Khoueiry, MD    323-865-0463      
Principal Investigator: Anthony El-Khoueiry, MD         
United States, Florida
University of Miami/Sylvester Comprehensive Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Marla Fonseca, CCRP    305-243-3360    mfonseca4@miami.edu   
Contact: Reisy Guedes, CCRC    (305) 243-8807    rxg957@med.miami.edu   
Principal Investigator: Cesar A Perez, MD         
Sponsors and Collaborators
Agenus Inc.
Investigators
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Study Director: Medical Director Agenus Inc.
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Responsible Party: Agenus Inc.
ClinicalTrials.gov Identifier: NCT04156100    
Other Study ID Numbers: C-900-01
First Posted: November 7, 2019    Key Record Dates
Last Update Posted: June 1, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms