Clinical Trials /

AGEN1884, an Anti-CTLA-4 Human Monoclonal Antibody in Subjects With Advanced or Refractory Cancer and Who Have Progressed With PD-1/PD-L1 Inhibitor as Their Most Recent Therapy

NCT02694822

Description:

This is an open-label, Phase 1/2, multicenter study to evaluate the safety, PK, and PD of an anti-CTLA-4 human monoclonal antibody (AGEN1884) in subjects with advanced or refractory cancer and in subjects who have progressed during treatment with a PD-1/PD-L1 inhibitor as their most recent therapy. The phase 1 portion of the study has been completed; It enrolled adult subjects with refractory, advanced cancer in a 3+3 dose escalation cohort. The phase 2 portions consists of approximately 40 patients who have progressed during treatment with an approved or investigational PD-1/PD-L1 inhibitor as their most recent therapy (2-6 weeks prior to first dose of study drug).

Related Conditions:
  • Hepatocellular Carcinoma
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: AGEN-1884, an Anti-CTLA-4 Antibody, in Advanced Solid Cancers
  • 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

Clinical Trial IDs

  • ORG STUDY ID: C-500-01
  • NCT ID: NCT02694822

Conditions

  • Advanced Solid Cancers

Interventions

DrugSynonymsArms
AGEN1884AGEN1884

Purpose

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..

Trial Arms

NameTypeDescriptionInterventions
AGEN1884Experimentalanti-CTLA-4 antibody
  • AGEN1884

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicities (DLTs) of AGEN1884.
Time Frame:1 year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:1 year
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:1 year
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:1 year
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:1 year
Safety Issue:
Description:
Measure:Explore biomarkers that may predict pharmacologic activity or response to AGEN1884.
Time Frame:1 year
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Agenus Inc.

Last Updated

April 15, 2017