Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors

Protocol: OSU-15169

Full Title

A Phase I Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination with MEDI4736 in Adult Subjects with Select Advanced Solid Tumors

Purpose

The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics,

Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination with MEDI4736 in

Adult Subjects with Select Advanced Solid Tumors

Are you eligible?

Inclusion Criteria:

Inclusion Criteria:

1. Adult subjects; age ≥ 18

2. Written and signed informed consent must be obtained

3. Have histologic or cytologic documentation of solid tumor

◦ Must have received and have progressed, are refractory, or are intolerant to

standard therapy appropriate for the specific tumor type. Depending on tumor type,

subjects should not have received more than 5 prior lines of therapy for recurrent or

metastatic disease including both standards of care and investigational therapies

4. Subjects must have at least 1 lesion that is measureable using RECIST guidelines

5. Subjects must consent to provide archived tumor specimens or tumor biopsies for

correlative biomarker studies.

6. All subjects are encouraged to consent to and provide paired pretreatment and

on-treatment tumor biopsies.

7. In the dose-expansion phase, all subjects are encouraged to consent and provide

paired pretreatment and on-treatment tumor biopsies

8. Eastern Cooperative Oncology Group performance score of 0 or 1

9. In the opinion of the investigator, likely to complete ≥ 56 days of treatment

10. Adequate organ function as determined by: I.Absolute neutrophil count ≥ 1.5 × 109/L

(1,500/mm3) II.Platelet count ≥ 75 × 109/L (75,000/mm3) III.Hemoglobin ≥ 9.0 g/dL

IV.Prothrombin time-international normalized ratio and partial thromboplastin time ≤

1.5 × ULN V.Calculated creatinine clearance* (CrCl) or 24 hour urine CrCl > 50

mL/minute VI.Total bilirubin ≤ 1.5 × ULN; for subjects with documented/suspected

Gilbert's disease, bilirubin ≤ 3 × UL VII.AST and ALT ≤ 2.5 × ULN VIII.Serum

electrolytes within normal limits

11. Female subjects of childbearing potential who are sexually active with a

non-sterilized male partner must use at least one highly effective method of

contraception from the time of screening, and must agree to continue using such

precautions for 90 days (or 180 days) after the final dose of investigational

product.

12. Nonsterilized males who are sexually active with a female partner of childbearing

potential must use condom plus spermicide from Day 1 through 90 days (or 180 days)

after receipt of the last dose of investigational product.

Exclusion Criteria:

1. Prior treatment with tumor necrosis factor receptor superfamily agonists including

OX40, CD27, CD137 (4-1BB), CD357 (GITR).

2. Subjects who have received prior therapy with regimens containing CTLA-4, PD-L1, or

PD-1 antagonists are NOT permitted to enroll unless all of the following apply:

Dose of immunotherapy must have been administered at least 28 days or 5 half

lives, whichever is shorter, prior to planned first dose of MEDI9447/MEDI4736

Must not have experienced a toxicity that led to permanent discontinuation of

prior immunotherapy

All AEs while receiving prior immunotherapy must have resolved to ≤ Grade 1 or

baseline prior to screening for this study

3. Must not have required the use of additional immunosuppression other than

corticosteroids for the management of an AE, not have experienced recurrence of an AE

if re-challenged, and not currently require maintenance doses of > 10 mg prednisone

or equivalent per day

4. Known allergy or hypersensitivity to investigational product formulations

5. History of more than one event of IRR requiring permanent discontinuation of IV drug

treatment

6. History of severe drug allergies or anaphylaxis to 2 or more food products or

medicine (including known sensitivity to acetaminophen/paracetamol, diphenhydramine

or equivalent antihistamine, and methylprednisolone or equivalent glucocorticoid)

7. Cardiac or peripheral vascular disease meeting any of the following criteria:

Past history of myocardial infarction in the prior 12 months

Past history of stroke or transient ischemic attack requiring medical therapy

Congestive heart failure ≥ Class 3 based on New York Heart Association

Functional Classification

8. Grade 3 or greater edema (eg, peripheral, pulmonary)

9. History of Grade 3 or greater thromboembolic events or unresolved thromboembolic

event of any grade

10. Subjects with active tuberculosis are ineligible. In settings where there is clinical

or radiographic evidence of tuberculosis, active disease must be ruled out

Exclusion Criteria:

Inclusion Criteria:

1. Adult subjects; age ≥ 18

2. Written and signed informed consent must be obtained

3. Have histologic or cytologic documentation of solid tumor

◦ Must have received and have progressed, are refractory, or are intolerant to

standard therapy appropriate for the specific tumor type. Depending on tumor type,

subjects should not have received more than 5 prior lines of therapy for recurrent or

metastatic disease including both standards of care and investigational therapies

4. Subjects must have at least 1 lesion that is measureable using RECIST guidelines

5. Subjects must consent to provide archived tumor specimens or tumor biopsies for

correlative biomarker studies.

6. All subjects are encouraged to consent to and provide paired pretreatment and

on-treatment tumor biopsies.

7. In the dose-expansion phase, all subjects are encouraged to consent and provide

paired pretreatment and on-treatment tumor biopsies

8. Eastern Cooperative Oncology Group performance score of 0 or 1

9. In the opinion of the investigator, likely to complete ≥ 56 days of treatment

10. Adequate organ function as determined by: I.Absolute neutrophil count ≥ 1.5 × 109/L

(1,500/mm3) II.Platelet count ≥ 75 × 109/L (75,000/mm3) III.Hemoglobin ≥ 9.0 g/dL

IV.Prothrombin time-international normalized ratio and partial thromboplastin time ≤

1.5 × ULN V.Calculated creatinine clearance* (CrCl) or 24 hour urine CrCl > 50

mL/minute VI.Total bilirubin ≤ 1.5 × ULN; for subjects with documented/suspected

Gilbert's disease, bilirubin ≤ 3 × UL VII.AST and ALT ≤ 2.5 × ULN VIII.Serum

electrolytes within normal limits

11. Female subjects of childbearing potential who are sexually active with a

non-sterilized male partner must use at least one highly effective method of

contraception from the time of screening, and must agree to continue using such

precautions for 90 days (or 180 days) after the final dose of investigational

product.

12. Nonsterilized males who are sexually active with a female partner of childbearing

potential must use condom plus spermicide from Day 1 through 90 days (or 180 days)

after receipt of the last dose of investigational product.

Exclusion Criteria:

1. Prior treatment with tumor necrosis factor receptor superfamily agonists including

OX40, CD27, CD137 (4-1BB), CD357 (GITR).

2. Subjects who have received prior therapy with regimens containing CTLA-4, PD-L1, or

PD-1 antagonists are NOT permitted to enroll unless all of the following apply:

Dose of immunotherapy must have been administered at least 28 days or 5 half

lives, whichever is shorter, prior to planned first dose of MEDI9447/MEDI4736

Must not have experienced a toxicity that led to permanent discontinuation of

prior immunotherapy

All AEs while receiving prior immunotherapy must have resolved to ≤ Grade 1 or

baseline prior to screening for this study

3. Must not have required the use of additional immunosuppression other than

corticosteroids for the management of an AE, not have experienced recurrence of an AE

if re-challenged, and not currently require maintenance doses of > 10 mg prednisone

or equivalent per day

4. Known allergy or hypersensitivity to investigational product formulations

5. History of more than one event of IRR requiring permanent discontinuation of IV drug

treatment

6. History of severe drug allergies or anaphylaxis to 2 or more food products or

medicine (including known sensitivity to acetaminophen/paracetamol, diphenhydramine

or equivalent antihistamine, and methylprednisolone or equivalent glucocorticoid)

7. Cardiac or peripheral vascular disease meeting any of the following criteria:

Past history of myocardial infarction in the prior 12 months

Past history of stroke or transient ischemic attack requiring medical therapy

Congestive heart failure ≥ Class 3 based on New York Heart Association

Functional Classification

8. Grade 3 or greater edema (eg, peripheral, pulmonary)

9. History of Grade 3 or greater thromboembolic events or unresolved thromboembolic

event of any grade

10. Subjects with active tuberculosis are ineligible. In settings where there is clinical

or radiographic evidence of tuberculosis, active disease must be ruled out