Colorectal Cancer (CRC), Head and Neck Squamous Cell Carcinoma (HNSCC), Metastatic Castration-resistant Prostate Cancer (mCRPC), Non Small Cell Lung Cancer Squamous (NSCLC-Sq), Pancreatic Ductal Adenocarcinoma (PDAC), Small Cell Lung Cancer (SCLC)
Conditions
Keywords
Medi7247, non small cell lung cancer, head and neck cancer, small cell lung cancer, colorectal cancer, prostate cancer, pancreatic adenocarcinoma
Brief summary
To assess safety and tolerability, describe the dose-limiting toxicities, assess the preliminary antitumor activity, determine the maximum tolerated dose (MTD) or the highest protocol-defined dose (maximum administered dose) in the absence of establishing the MTD, and a recommended dose for further evaluation of MEDI7247 in patients with selected advanced or metastatic solid tumor malignancies that have received at least 1 prior line of treatment.
Interventions
DRUGMEDI7247
Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
Sponsors
MedImmune LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 101 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed diagnosis of advanced or metastatic select solid tumors and either progression on or documented intolerance to standard therapies 2. Age ≥ 18 years at the time of screening. 3. Written informed consent and any locally required authorization 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 5. At least 1 measurable target lesion by CT or MRI per RECIST Version 1.1 (excluding mCRPC) 6. Adequate Liver Function: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × ULN (upper limit normal), Albumin \> 3 g/dL, and serum total bilirubin (TBL) ≤ 1.5 × ULN; (unless bilirubin rise is due to Gilbert's syndrome, hepatic metastases or of non-hepatic origin, in which case TBL ≤ 3 × ULN is allowed) 7. Creatinine Clearance (CrCL) ≥ 40 mL/min 8. Adequate Hematopoesis: Absolute Neutrophil Count (ANC) ≥ 1,500/μL, Platelets ≥ 100,000/μL, and Hgb ≥ 9 g/dL unassisted by transfusion or growth factor within 14 days of screening 9. Provision of archival or fresh tumor tissue at screening 10. Female patients of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception, and must agree to continue using such precautions for 90 days after the last dose of investigational product. 11. Nonsterilized male patients who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from 7 days post-screening and for 90 days after receipt of the last dose of investigational product.
Exclusion criteria
1. Active central nervous system (CNS) metastases, unless adequately treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) and prednisolone 10 mg or less for more than 2 weeks prior to enrollment. For SCLC, a brain MRI scan that was conducted ≤ 28 days from Day 1 is required. 2. Residual toxicity from prior anticancer therapy not resolved to NCI CTCAE v4.03 Grade 1, with the exception of alopecia/vitiligo at the time of first dose of investigational product. For patients previously receiving immunotherapy, toxicities that are unlikely to recover to Grade 1. 3. Royal Marsden Hospital (RMH) prognostic score 2 and 3 at baseline. 4. Treatment with anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 21 days, or prior palliative radiotherapy within 2 weeks of the first dose of investigational product. 5 Prior treatment with other Pyrrolobenzodiazepine-Antibody Drug Conjugates. 6 History of previous malignancies (except for locally curable cancers) unless a complete remission was achieved at least 3 years prior to study entry AND no additional therapy is required during the study period (except adjuvant hormonal therapy and bisphosphonate). 7\. Failure to recover from major surgery or significant traumatic injury within 21 days of first dose of study treatment. 8 History of hepatic sinusoidal obstruction syndrome, also called veno-occlusive disease 9. History of capillary leak syndrome. 10 Blood transfusion within 14 days of study entry except when needed for disease related anemia. 11\. New York Heart Association classes III-IV congestive heart failure or serious cardiac arrhythmia requiring treatment, history of myocardial infarction, unstable angina, vascular stent, or coronary artery bypass graft within 6 months of the first dose of investigational product. 12. Active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infections at the time of screening. 13\. Current severe active systemic disease including active concurrent malignancy 14. Pregnancy and/or breastfeeding at time of screening 15. Concurrent enrollment in anther clinical study involving an investigational treatment that is not an extension of another MedImmune study with the same investigational product.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Adverse Events | From time of informed consent through 90 days post end of treatment | To assess the occurrence of adverse events |
| Occurrence of Serious Adverse Events | From time of informed consent through 90 days post end of treatment | To assess the occurrence of serious adverse events |
| Occurrence of Dose Limiting Toxicities | During the evaluation period of 21 days post first dose | To assess the occurrence of toxicities and abnormal laboratory results that may limit further dose administration |
| Number of patients with changes in laboratory parameters from baseline | From time of informed consent through 90 days post end of treatment | To assess serum chemistry, hematology, urinalysis and coagulation parameters |
| Number of patients with changes in vital signs parameters from baseline | from time of informed consent through 21 days post last dose | to assess changes in vital signs |
| Number of patients with changes in electrocardiogram results from baseline | from time of informed consent through 21 days post last dose | to assess changes in ECG |
| Percentage of patients with changes in laboratory parameters from baseline | from time of informed consent through 90 days post end of treatment | to assess changes in serum chemistry, hematology, urinalysis, and coagulation parameters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response (TTR) | From time of informed consent and up to 90 days post end of treatment | To assess antitumor activity of MEDI7247 |
| Duration of Response (DoR) | From time of informed consent and up to 2 years after last subject in | To assess antitumor activity of MEDI7247 |
| MEDI7247 maximum observed concentration (Cmax) | From first dose through 90 days post end of treatment | To characterize MEDI7247 single agent Pharmacokinetics |
| Disease Control (DC) | From time of informed consent and up to 2 years after last subject in | To assess antitumor activity of MEDI7247 |
| Overall Survival (OS) | From time of informed consent and up to 2 years after last subject in | To assess antitumor activity of MEDI7247 |
| Progression Free Survival (PFS) | From time of informed consent and up to 2 years after last subject in | To assess the antitumor activity of MEDI7247 |
| MEDI7247 terminal half life (t1/2) | From first dose through 90 days post end of treatment | To characterize single agent MEDI7247 pharmacokinetics |
| MEDI7247 area under the concentration/time curve (AUC) | from first dose through 90 days post end of treatment | To characterize single agent MEDI7247 pharmacokinetics |
| MEDI7247 clearance | from first dose through 90 days post end of treatment | to characterize the single agent MEDI7247 pharmacokinetics |
| Number of subjects who develop anti-drug antibodies | first dose through 90 days post end of treatment | To characterize MEDI7247 immunogenicity |
| Best Overall Response | From time of informed consent and up to 90 days post end of treatment | To assess antitumor activity of MEDI7247 |
| Objective Response Rate (ORR) | From time of informed consent and up to 2 years after last subject in | To assess antitumor activity of MEDI7247 |
Countries
Canada, United States
Outcome results
None listed