Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

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

Protocol: OSU-15281

Full Title

A Phase 1 Open-label, Multicenter 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

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 followed by an

MTD expansion cohort of immunotherapy-experienced and immunotherapy-naïve subjects.

Are you eligible?

Inclusion 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 (Appendix B).

5. Life expectancy ≥12 weeks.

6. Adequate cardiac function (≤New York Heart Association [NYHA] Class II) (Appendix C).

7. Adequate organ function defined as absolute neutrophil count ≥1,500×106/L, absolute

lymphocyte count ≥500/mm3, and platelet count ≥100,000×106/mm3. 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 e

Exclusion 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 (Appendix B).

5. Life expectancy ≥12 weeks.

6. Adequate cardiac function (≤New York Heart Association [NYHA] Class II) (Appendix C).

7. Adequate organ function defined as absolute neutrophil count ≥1,500×106/L, absolute

lymphocyte count ≥500/mm3, and platelet count ≥100,000×106/mm3. 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 e