A Phase 1/1b Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI7247 in Patients With Advanced or Metastatic Disease in Selected Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- MEDI7247
- Conditions
- Non Small Cell Lung Cancer Squamous (NSCLC-Sq)
- Sponsor
- MedImmune LLC
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Number of patients with changes in laboratory parameters from baseline
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Confirmed diagnosis of advanced or metastatic select solid tumors and either progression on or documented intolerance to standard therapies
- •Age ≥ 18 years at the time of screening.
- •Written informed consent and any locally required authorization
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •At least 1 measurable target lesion by CT or MRI per RECIST Version 1.1 (excluding mCRPC)
- •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)
- •Creatinine Clearance (CrCL) ≥ 40 mL/min
- •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
- •Provision of archival or fresh tumor tissue at screening
- •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.
Exclusion Criteria
- •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.
- •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
- •Royal Marsden Hospital (RMH) prognostic score 2 and 3 at baseline.
- •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).
- •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
- •History of capillary leak syndrome. 10 Blood transfusion within 14 days of study entry except when needed for disease related anemia.
- •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.
Arms & Interventions
NSCLC-Sq/HNSCC
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.
Intervention: MEDI7247
Small Cell Lung Cancer
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.
Intervention: MEDI7247
Colorectal Cancer
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.
Intervention: MEDI7247
Pancreatic Ductal Adenocarcinoma
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.
Intervention: MEDI7247
Metastatic Castration-Resistant Prostate Cancer
Patients with mCRPC who have received prior treatment with abiraterone or enzalutamide, with or without a prior taxane-based chemotherapy in the mCRPC setting.
Intervention: MEDI7247
Other advanced/metastatic target expressing solid tumors
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
Intervention: MEDI7247
Outcomes
Primary Outcomes
Number of patients with changes in laboratory parameters from baseline
Time Frame: From time of informed consent through 90 days post end of treatment
To assess serum chemistry, hematology, urinalysis and coagulation parameters
Occurrence of Adverse Events
Time Frame: From time of informed consent through 90 days post end of treatment
To assess the occurrence of adverse events
Occurrence of Serious Adverse Events
Time Frame: From time of informed consent through 90 days post end of treatment
To assess the occurrence of serious adverse events
Number of patients with changes in electrocardiogram results from baseline
Time Frame: from time of informed consent through 21 days post last dose
to assess changes in ECG
Occurrence of Dose Limiting Toxicities
Time Frame: 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 vital signs parameters from baseline
Time Frame: from time of informed consent through 21 days post last dose
to assess changes in vital signs
Percentage of patients with changes in laboratory parameters from baseline
Time Frame: from time of informed consent through 90 days post end of treatment
to assess changes in serum chemistry, hematology, urinalysis, and coagulation parameters
Secondary Outcomes
- Number of subjects who develop anti-drug antibodies(first dose through 90 days post end of treatment)
- Objective Response Rate (ORR)(From time of informed consent and up to 2 years after last subject in)
- MEDI7247 area under the concentration/time curve (AUC)(from first dose through 90 days post end of treatment)
- MEDI7247 clearance(from first dose through 90 days post end of treatment)
- MEDI7247 terminal half life (t1/2)(From first dose through 90 days post end of treatment)
- MEDI7247 maximum observed concentration (Cmax)(From first dose through 90 days post end of treatment)
- Best Overall Response(From time of informed consent and up to 90 days post end of treatment)
- Overall Survival (OS)(From time of informed consent and up to 2 years after last subject in)
- Time to Response (TTR)(From time of informed consent and up to 90 days post end of treatment)
- Duration of Response (DoR)(From time of informed consent and up to 2 years after last subject in)
- Progression Free Survival (PFS)(From time of informed consent and up to 2 years after last subject in)
- Disease Control (DC)(From time of informed consent and up to 2 years after last subject in)