Protocol No.: OCR15355
Sponsor Protocol No.: D6070C00001; MEDI9447
A Phase 1 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
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
Phase: Phase I
Age Group: Adult
Arm 1: MEDI9447 only
Arm 2: MEDI9447 and MEDI4736
1. Ages 18 years-old or older
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:
- Absolute neutrophil count >= 1.5 × 109/L (1,500/mm3)
- Platelet count >= 75 × 109/L (75,000/mm3)
- Hemoglobin >= 9.0 g/dL
- Prothrombin time-international normalized ratio and partial thromboplastin time = - Calculated creatinine clearance* (CrCl) or 24 hour urine CrCl > 50 mL/minute
- Total bilirubin = - AST and ALT = - 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.
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)
** Contact study team for complete listing of eligibility criteria
Applicable Disease Sites
UF Gainesville : Marlene Sarmiento
Marlene Sarmiento, RN
Phone: +1 352-265-0680 ext. 50704
View study listing on ClinicialTrials.gov