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Phase 1 / 2 Study of AGEN2034 in Advanced Tumors and Cervical Cancer

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ClinicalTrials.gov Identifier: NCT03104699
Recruitment Status : Recruiting
First Posted : April 7, 2017
Last Update Posted : March 5, 2018
Sponsor:
Information provided by (Responsible Party):
Agenus Inc.

Brief Summary:
This is a Phase 1, open-label, 3 + 3 dose-escalation trial in subjects with metastatic or locally advanced solid tumors, with a consecutive Phase 2 expansion to evaluate efficacy in subjects with recurrent, unresectable, or metastatic (advanced) cervical cancer that has progressed after a platinum doublet.

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN2034 in Subjects With Metastatic or Locally Advanced Solid Tumors, With Expansion to Second-Line Cervical Cancer
Actual Study Start Date : April 11, 2017
Estimated Primary Completion Date : March 1, 2019
Estimated Study Completion Date : September 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: AGEN2034
anti-PD-1 antibody
Drug: AGEN2034
anti-PD-1 antibody



Primary Outcome Measures :
  1. Dose limiting toxicities (DLTs) of AGEN2034 [ Time Frame: 3 weeks ]
    Occurrence of DLTs during first 3 weeks of treatment in the dose escalation part of the study

  2. Maximum tolerated dose (MTD) [ Time Frame: 1 year ]
    MTD for administration in the expansion part of the study

  3. Best overall response (BOR) according to Response Evaluation Criteria in solid tumors (Phase 2 expansion) [ Time Frame: 1 year ]
    BOR confirmed per RECIST 1.1 and investigator assessment


Secondary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) of AGEN2034 [ Time Frame: 1 year ]
    Understanding PK

  2. Area Under the Curve (AUC) of AGEN2034 [ Time Frame: 1 year ]
    Understanding PK

  3. Progression-free survival (PFS) [ Time Frame: 1 year ]
    Time from first treatment to first observation of documented disease progression

  4. Duration of response (DOR) [ Time Frame: 1 year ]
    Time from first observation of response to first observation of documented disease progression

  5. Overall survival (OS) [ Time Frame: 1 year ]
    Time from first treatment to death



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

Inclusion Criteria:

  • Safety Cohort (Dose Escalation)

    1. Signed written informed consent.
    2. Age ≥18 years.
    3. Histologically or cytologically proven metastatic or locally advanced solid tumors for which no standard therapy exists or standard therapy has failed. Availability of tumor archival material or fresh biopsies is optional for subjects in dose escalation.
    4. ECOG performance status of 0 to 1 at trial entry and estimated life expectancy of ≥3 months.
    5. Evidence of objective disease. A measurable lesion is not necessary.
    6. Adequate hematological function defined by white blood cell (WBC) count ≥3 × 10^9/L; absolute neutrophil count (ANC) ≥1.5 × 10^9/L; lymphocyte count ≥0.5 × 10^9/L; platelet count ≥100 × 10^9/L; and hemoglobin ≥9 g/dL (may have been transfused).
    7. Adequate hepatic function, defined as total bilirubin ≤1.5 × upper limit of normal (ULN); AST ≤2.5 × ULN; and ALT ≤2.5 × ULN. For subjects with documented metastatic disease to the liver, AST and ALT: ≤5 × ULN.
    8. Adequate renal function, defined as estimated creatinine clearance >50 mL/min according to Cockcroft-Gault formula or measured 24-hour creatinine clearance (or local institutional standard method).
    9. Effective contraception for both male and female subjects if risk of conception exists.
  • Efficacy Expansion Cohort (Second-Line Cervical Cancer)

    1. Signed written informed consent.
    2. Age ≥18 years.
    3. Subjects must have recurrent, unresectable, or metastatic cervical cancer and have relapsed after a platinum-containing doublet administered for treatment of advanced (recurrent, unresectable, or metastatic) disease.

      Subjects must have persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix, with documented disease progression (disease not amenable to curative therapy).

      Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric type adenocarcinoma, clear cell carcinoma and mesonephric carcinoma. Histologic confirmation of the original primary tumor is required via pathology report.

      Subjects must have had one prior systemic chemotherapeutic regimen for management of persistent, recurrent, or metastatic carcinoma of the cervix (e.g., paclitaxel/cisplatin, paclitaxel/cisplatin/bevacizumab). Chemotherapy administered concurrently with primary radiation (e.g., weekly cisplatin) is not counted as a systemic chemotherapy regimen. Adjuvant chemotherapy given following completion of radiation therapy (or concurrent chemotherapy and radiation therapy) is not counted as a systemic chemotherapy regimen (e.g., paclitaxel and carboplatin for ≤4 cycles).

      Note: Subjects who have received >1 prior regimen are not eligible.

    4. ECOG performance status of 0 to 1 at trial entry and estimated life expectancy of ≥3 months.
    5. Availability of a formalin-fixed paraffin-embedded block containing tumor tissue or 7 unstained tumor slides suitable for PD-L1 expression assessment.
    6. Availability of tissue for HPV testing (paraffin block or one 7-µm section on a slide).
    7. Disease must be measurable, with ≥1 unidimensional measurable lesion per RECIST 1.1.
    8. Adequate hematological function, defined as WBC ≥3 × 10^9/L; ANC ≥1.5 × 10^9/L; lymphocyte count ≥0.5 × 10^9/L; platelet count ≥100 × 10^9/L; and hemoglobin ≥9 g/dL (may have been transfused).
    9. Adequate hepatic function, defined as total bilirubin ≤1.5 × ULN; AST ≤2.5 × ULN; and ALT ≤2.5 × ULN.
    10. Adequate renal function, defined as estimated creatinine clearance >30 mL/min according to Cockcroft-Gault formula or measured 24-hour creatinine clearance (or local institutional standard method).
    11. Effective contraception for female subjects if risk of conception exists. Note: Effects of the study drug on the developing human fetus are unknown. Thus, women of childbearing potential and men must agree to use effective contraception, defined as 2 barrier methods, or 1 barrier method with a spermicide, an intrauterine device or use of oral female contraceptive. Effective contraception must be used 30 days before first study drug administration, for the duration of trial participation, and ≥60 days after stopping trial participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately.

Exclusion Criteria:

  • Safety and Expansion Cohorts

    1. Concurrent treatment with a non-permitted drug.
    2. 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. For subjects with metastatic melanoma, prior treatment with CTLA-4-blocking antibody is permissible.
    3. Concurrent anticancer treatment (e.g., cytoreductive therapy, radiotherapy except for palliative bone-directed radiotherapy, immune therapy, or cytokine therapy except for erythropoietin) within 28 days before start of trial treatment; major surgery within 28 days before start of trial treatment (excluding prior diagnostic biopsy); use of hormonal agents within 7 days before start of trial treatment, except for subjects with castration-resistant prostate cancer (CRPC), who may remain on treatment with luteinizing hormone-releasing hormone agonists or antagonists; or use of any investigational drug within 28 days before start of trial treatment.

      Note: Small molecule or antibody targeted therapy is permissible <14 days from start of trial treatment.

    4. Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs 14 days before initiation of study treatment. Steroids with no or minimal systemic effect (topical, inhalation) are allowed.

      Note: Subjects receiving bisphosphonate or denosumab are eligible provided that treatment was initiated ≥14 days before first dose of AGEN2034.

      Note: Use of inhaled or topical corticosteroid is permitted. Note: Steroid pre-medication for radiographic imaging for dye allergies is permitted.

    5. Previous malignant disease (other than target malignancy to be investigated in this trial) within the last 5 years, with the exception of basal or squamous cell carcinoma of the skin.
    6. Rapidly progressive disease.
    7. Active or history of central nervous system metastases.
    8. Receipt of any organ transplantation, including allogeneic stem-cell transplantation.
    9. Significant acute or chronic infections, including:

      • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
      • Positive test for hepatitis B virus (HBV) surface antigen and/or confirmatory hepatitis C virus (HCV) RNA (if anti-HCV antibody tested positive).
    10. Active or history of any autoimmune disease (subjects with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies.
    11. 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).
    12. Persisting toxicity related to prior therapy of NCI CTCAE grade >1 severity. Sensory neuropathy of grade ≤2 is acceptable.
    13. Pregnancy or breast feeding.
    14. Known alcohol or drug abuse.
    15. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (<6 months before enrollment), myocardial infarction (<6 months before enrollment), unstable angina, congestive heart failure (New York Heart Association class ≥II), or serious uncontrolled cardiac arrhythmia requiring medication.
    16. All other significant diseases (e.g., inflammatory bowel disease) that, in the opinion of the investigator, might impair the subject's tolerance of trial treatment.
    17. Any psychiatric condition that would prohibit understanding or rendering of informed consent.
    18. Legal incapacity or limited legal capacity.
    19. Vaccination within 4 weeks of first dose of AGEN2034 and while on study except for administration of inactivated vaccines (e.g., inactivated influenza vaccines).

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): NCT03104699


Contacts
Contact: Agenus Study Team 781-674-4562 AGEN2034@agenusbio.com

Locations
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Clinical trials hotline    626-218-1133      
Contact: Toll Free:    877-467-3411      
Principal Investigator: Edward Wang, MD         
United States, Florida
School of Medicine at the University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Yvonne Dinh    305-243-9899    y.dinh@med.miami.edu   
United States, Ohio
The Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Sarah Ferguson       sarah.ferguson@osumc.edu   
Principal Investigator: David O'Malley, MD         
United States, Oklahoma
University of Oklahoma Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Dena Suthers    405-271-8001 ext 48971    PhaseI-Referrals@ouhsc.edu   
Principal Investigator: Kathleen Moore, MD         
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Contact       cancerresearch@swedish.org   
Principal Investigator: Charles Drescher, MD         
Sponsors and Collaborators
Agenus Inc.
Investigators
Study Director: Igor Proscurshim, MD Agenus Inc.

Responsible Party: Agenus Inc.
ClinicalTrials.gov Identifier: NCT03104699     History of Changes
Other Study ID Numbers: C-700-01
First Posted: April 7, 2017    Key Record Dates
Last Update Posted: March 5, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Agenus Inc.:
Antibodies
Immunologic effects
Physiological Effects of Drugs

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
Antibodies
Immunologic Factors
Physiological Effects of Drugs