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AGEN-1884, an Anti-CTLA-4 Antibody, in Advanced Solid Cancers

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ClinicalTrials.gov Identifier: NCT02694822
Recruitment Status : Recruiting
First Posted : March 1, 2016
Last Update Posted : June 27, 2017
Sponsor:
Information provided by (Responsible Party):
Agenus Inc.

Brief Summary:
This is an open-label, Phase 1, multicenter study to evaluate the safety, PK, and PD of an anti-CTLA-4 human monoclonal antibody (AGEN1884) and to estimate the MTD in subjects with advanced or refractory cancer. The study will consist of a 3+3 dose escalation cohort starting at a near minimally anticipated biologic effect level (MABEL) dose with expansion cohorts at 1 mg/kg and 3 mg/kg..

Condition or disease Intervention/treatment Phase
Advanced Solid Cancers Drug: AGEN1884 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study To Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of an Anti-CTLA-4 Human Monoclonal Antibody (AGEN1884), and to Estimate the Maximum Tolerated Dose in Subjects With Advanced or Refractory Cancer
Study Start Date : April 2016
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : October 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AGEN1884
anti-CTLA-4 antibody
Drug: AGEN1884
anti-CTLA-4 antibody




Primary Outcome Measures :
  1. Dose limiting toxicities (DLTs) of AGEN1884. [ Time Frame: 1 year ]
  2. Maximum tolerated dose MTD. [ Time Frame: 1 year ]
  3. Concentration of AGEN1884 on Day 1 at 2, 6 and 24 hours and on Day 8, Day 15 and Day 22. [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 1 year ]
  2. Duration of response (DOR) [ Time Frame: 1 year ]
  3. Progression-free survival (PFS) [ Time Frame: 1 year ]
  4. Overall survival (OS) [ Time Frame: 1 year ]
  5. Explore biomarkers that may predict pharmacologic activity or response to AGEN1884. [ Time Frame: 1 year ]


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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. Sign informed consent.
  2. ≥18 years of age.
  3. Histological or cytological diagnosis of solid cancer or lymphoma that is considered incurable and without therapies with established benefit. Biopsy is not necessary for subjects with known prior diagnosis and clinical or radiographic evidence of recurrence.
  4. Eastern Cooperative Oncology Group score of 0 or 1.
  5. Life expectancy ≥12 weeks.
  6. Adequate cardiac function (≤New York Heart Association [NYHA] Class II).
  7. Adequate organ function defined as absolute neutrophil count ≥1,500×10^6/L, absolute lymphocyte count ≥500/mm^3, and platelet count ≥100,000×10^6/mm^3. Adequate liver function defined as aspartate aminotransferase and alanine aminotransferase ≤2.5× the upper limit of institutional normal, bilirubin ≤1.5 mg/dL or 25 µmol/L. Adequate renal function defined as blood urea nitrogen and serum creatinine of ≤1.5 mg/dL or 130 µmol/L.
  8. Female subjects of childbearing potential and fertile male subjects must agree to use adequate contraception or abstain from sexual activity from the time of consent through 90 days after the end of study drug. Adequate contraception includes condoms with contraceptive foam; oral, implantable, or injectable contraceptives; contraceptive patch; intrauterine device; diaphragm with spermicidal gel; or a sexual partner who is surgically sterilized or postmenopausal.

Exclusion Criteria

  1. Other malignancies treated within the last 5 years, except in situ cervix carcinoma or non-melanoma skin cancer.
  2. Other form(s) of antineoplastic therapy anticipated during the period of the study.
  3. Previous severe hypersensitivity reaction to another monoclonal antibody, such as colitis or pneumonitis requiring treatment with steroids, or has a history of interstitial lung disease.
  4. History of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, or abdominal carcinomatosis.
  5. Primary or secondary immunodeficiency (including immunosuppressive disease, autoimmune disease [including autoimmune endocrinopathies, such as hypothyroidism, and insulin dependent diabetes mellitus], or usage of immunosuppressive medications).
  6. Subjects with a known history of human immunodeficiency virus 1 and 2, human T lymphotropic virus 1, hepatitis B virus, or active hepatitis C virus.
  7. Subjects with a history of connective tissue disorders.
  8. Receipt of anticancer medications or investigational drugs within the following intervals before the first administration of study drug:

    1. ≤14 days for chemotherapy, targeted small molecule therapy, or radiation therapy. Subjects must also not have had radiation pneumonitis as a result of treatment, and cannot participate in the study if they are on chronic corticosteroids for radiation pneumonitis. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with sponsor approval.

      Note: Bisphosphonates and denosumab are permitted medications.

    2. ≤28 days for a prior immunotherapy. No prior therapy with check point inhibitors, costimulatory agonists or immunomodulatory agents is allowed.
    3. ≤28 days for prior monoclonal antibody used for anticancer therapy with the exception of denosumab.
    4. ≤28 days for prior systemic corticosteroid therapy.
    5. ≤7 days for immune-suppressive-based treatment for any reason. Note: Use of inhaled or topical corticosteroid use for radiographic procedures is permitted.

      Note: The use of physiologic corticosteroid replacement therapy may be approved after consultation with the sponsor.

    6. ≤28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational study drugs or devices.
  9. Has not recovered to Grade ≤1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting therapy.

    Note: Subjects with Grade ≤2 neuropathy is an exception and may enroll.

  10. Uncontrolled infection or other serious medical illnesses.
  11. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. Screening corrected QT (QTc) interval > 470 msec is excluded (corrected by Fridericia). If a single QTc is > 470 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is < 470 milliseconds. For subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds), the JTc interval may be used in place of the QTc with sponsor approval. The JTc must be < 340 milliseconds if JTc is used in place of the QTc. Subjects with left bundle branch block are excluded.

    Note: QTc prolongation due to pacemaker may enroll if the JTc is normal or with medical monitor approval.

  12. Any medications that are known to prolong the QTc interval.
  13. Any medical conditions that, in the opinion of the investigator, would preclude use of AGEN1884, including AGEN1884 hypersensitivity.
  14. Women who are pregnant or breast-feeding.
  15. Concurrent participation in other investigational drug trials.
  16. Subjects with a history of or active CNS tumors or metastases from non-CNS tumors.

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): NCT02694822


Contacts
Contact: Agenus Medical Monitor, MD 781-674-4508

Locations
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   
Principal Investigator: Breelyn A Wilky, MD         
United States, Illinois
Comprehensive Cancer Center of Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Amy Hoyer, MS, CCRC    312-695-1341      
Principal Investigator: Priya Kumthekar, MD         
United States, North Carolina
Levine Cancer Institute Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Chari Granger, RN, BSN, OCN    980-442-5225      
Principal Investigator: Jimmy Hwang, MD         
United States, Ohio
The Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Debbie Wilson    614-685-6456    debbie.wilson@osumc.edu   
Principal Investigator: Robert Wesolowski, MD         
Sponsors and Collaborators
Agenus Inc.
Investigators
Study Director: Igor Proscurshim, MD Agenus Inc.

Responsible Party: Agenus Inc.
ClinicalTrials.gov Identifier: NCT02694822     History of Changes
Other Study ID Numbers: C-500-01
First Posted: March 1, 2016    Key Record Dates
Last Update Posted: June 27, 2017
Last Verified: June 2017
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

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs