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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NSCLC-Sq/HNSCC | Experimental | Patients with advanced or metastatic NSCLC-Sq or HNSCC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior standard of care regimen (platinum-based for HNSCC). PDL-1 positive patients should have received previous PD-1 or PD-L1 inhibitor where available. |
|
| Small Cell Lung Cancer | Experimental | Patients with advanced SCLC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior standard of care regimen. |
|
| Colorectal Cancer | Experimental | Patients with metastatic adenocarcinoma of the colon or rectum who have received and have progressed, or have documented intolerance, on prior thymidylate synthase inhibitor (eg, 5-fluorouracil (5-FU), capecitabine, raltitrexed, tegafur-uracil (UFT), irinotecan, and oxaliplatin for metastatic disease. If patients progress within 6 months of their last dose of adjuvant therapy this should be considered as a line of therapy in the metastatic setting. Patients with known RAS wildtype tumors must have received and progressed, or have documented intolerance, on anti-EGFR antibody. Patients with microsatellite instability-high or deficient mismatch repair tumors, must have received and progressed, or have documented intolerance on a PD-1 inhibitor, or PD-1 inhibitor plus cytotoxic T-lymphocyte antigen-4 inhibitor treatment where available. |
|
| Pancreatic Ductal Adenocarcinoma | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MEDI7247 | Drug | Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule |
|
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of Adverse Events | To assess the occurrence of adverse events | From time of informed consent through 90 days post end of treatment |
| Occurrence of Serious Adverse Events | To assess the occurrence of serious adverse events | From time of informed consent through 90 days post end of treatment |
| Occurrence of Dose Limiting Toxicities | To assess the occurrence of toxicities and abnormal laboratory results that may limit further dose administration | During the evaluation period of 21 days post first dose |
| Number of patients with changes in laboratory parameters from baseline | To assess serum chemistry, hematology, urinalysis and coagulation parameters | From time of informed consent through 90 days post end of treatment |
| Number of patients with changes in vital signs parameters from baseline | to assess changes in vital signs | from time of informed consent through 21 days post last dose |
| Number of patients with changes in electrocardiogram results from baseline | to assess changes in ECG | from time of informed consent through 21 days post last dose |
| Percentage of patients with changes in laboratory parameters from baseline | to assess changes in serum chemistry, hematology, urinalysis, and coagulation parameters |
| Measure | Description | Time Frame |
|---|---|---|
| MEDI7247 maximum observed concentration (Cmax) | To characterize MEDI7247 single agent Pharmacokinetics | From first dose through 90 days post end of treatment |
| MEDI7247 terminal half life (t1/2) |
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Inclusion Criteria:
Exclusion Criteria:
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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Huntersville | North Carolina | 28078 | United States | ||
| Research Site |
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Patients with unresectable, locally advanced or metastatic PDAC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior line of treatment.
|
| Metastatic Castration-Resistant Prostate Cancer | Experimental | Patients with mCRPC who have received prior treatment with abiraterone or enzalutamide, with or without a prior taxane-based chemotherapy in the mCRPC setting. |
|
| Other advanced/metastatic target expressing solid tumors | Experimental | Patients with advanced or metastatic solid tumors not defined by other treatment arms who have positive expression of the protein target and have exhausted all approved therapies |
|
| from time of informed consent through 90 days post end of treatment |
To characterize single agent MEDI7247 pharmacokinetics
| From first dose through 90 days post end of treatment |
| MEDI7247 area under the concentration/time curve (AUC) | To characterize single agent MEDI7247 pharmacokinetics | from first dose through 90 days post end of treatment |
| MEDI7247 clearance | to characterize the single agent MEDI7247 pharmacokinetics | from first dose through 90 days post end of treatment |
| Number of subjects who develop anti-drug antibodies | To characterize MEDI7247 immunogenicity | first dose through 90 days post end of treatment |
| Best Overall Response | To assess antitumor activity of MEDI7247 | From time of informed consent and up to 90 days post end of treatment |
| Objective Response Rate (ORR) | To assess antitumor activity of MEDI7247 | From time of informed consent and up to 2 years after last subject in |
| Time to Response (TTR) | To assess antitumor activity of MEDI7247 | From time of informed consent and up to 90 days post end of treatment |
| Duration of Response (DoR) | To assess antitumor activity of MEDI7247 | From time of informed consent and up to 2 years after last subject in |
| Progression Free Survival (PFS) | To assess the antitumor activity of MEDI7247 | From time of informed consent and up to 2 years after last subject in |
| Disease Control (DC) | To assess antitumor activity of MEDI7247 | From time of informed consent and up to 2 years after last subject in |
| Overall Survival (OS) | To assess antitumor activity of MEDI7247 | From time of informed consent and up to 2 years after last subject in |
| Nashville |
| Tennessee |
| 37203 |
| United States |
| Research Site | Toronto | Ontario | M5G 2M9 | Canada |
| ID | Term |
|---|---|
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| D055752 | Small Cell Lung Carcinoma |
| D015179 | Colorectal Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D006258 | Head and Neck Neoplasms |
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009371 | Neoplasms by Site |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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