Brief Summary
To evaluate the safety and tolerability of MEDI0562 in adult subjects with selected advanced solid tumors
Brief Title
A Phase 1 Study of MEDI0562 in Adult Subjects With Selected Advanced Solid Tumors
Detailed Description
This is a first-time-in-human (FTiH) Phase 1, multicenter, open-label, dose-escalation, and dose-expansion study of MEDI0562 to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics and preliminary anti-tumor activity in adult subjects with selected advanced solid tumors.
Completion Date
Completion Date Type
Actual
Conditions
Advanced Solid Tumors
Eligibility Criteria
Inclusion Criteria:
* Subjects must have confirmed advanced solid tumor and have progressed, are refractory, or are intolerant to standard therapy appropriate for tumor type. Subjects should not have received more than 3 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies.
* Subjects must have at least 1 measurable lesion.
* Consent to provide archived tumor specimens
* Willingness to undergo pre-treatment and on-treatment biopsy.
* Adequate organ function.
* Use of highly effective contraception (females) or male condom plus spermicide (males).
Exclusion Criteria:
* Prior treatment with TNFRSF agonists.
* Subjects who have received certain prior immunotherapy or had toxicities relating to prior immunotherapy may not be permitted to enroll.
o Must not have required the use of additional immunosuppression other than corticosteroids for the management of an adverse event.
* History of severe allergic reactions to any unknown allergens or any components of the study drug formulations.
* Receipt of any conventional or investigational anticancer therapy within 28 days prior to the first dose of MEDI0562.
* Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment.
* Unresolved toxicities from prior anticancer therapy.
* Any condition that, in the opinion of the investigator or sponsor, would interfere with evaluation of the investigational product.
* Subjects must have confirmed advanced solid tumor and have progressed, are refractory, or are intolerant to standard therapy appropriate for tumor type. Subjects should not have received more than 3 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies.
* Subjects must have at least 1 measurable lesion.
* Consent to provide archived tumor specimens
* Willingness to undergo pre-treatment and on-treatment biopsy.
* Adequate organ function.
* Use of highly effective contraception (females) or male condom plus spermicide (males).
Exclusion Criteria:
* Prior treatment with TNFRSF agonists.
* Subjects who have received certain prior immunotherapy or had toxicities relating to prior immunotherapy may not be permitted to enroll.
o Must not have required the use of additional immunosuppression other than corticosteroids for the management of an adverse event.
* History of severe allergic reactions to any unknown allergens or any components of the study drug formulations.
* Receipt of any conventional or investigational anticancer therapy within 28 days prior to the first dose of MEDI0562.
* Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment.
* Unresolved toxicities from prior anticancer therapy.
* Any condition that, in the opinion of the investigator or sponsor, would interfere with evaluation of the investigational product.
Inclusion Criteria
Inclusion Criteria:
* Subjects must have confirmed advanced solid tumor and have progressed, are refractory, or are intolerant to standard therapy appropriate for tumor type. Subjects should not have received more than 3 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies.
* Subjects must have at least 1 measurable lesion.
* Consent to provide archived tumor specimens
* Willingness to undergo pre-treatment and on-treatment biopsy.
* Adequate organ function.
* Use of highly effective contraception (females) or male condom plus spermicide (males).
* Subjects must have confirmed advanced solid tumor and have progressed, are refractory, or are intolerant to standard therapy appropriate for tumor type. Subjects should not have received more than 3 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies.
* Subjects must have at least 1 measurable lesion.
* Consent to provide archived tumor specimens
* Willingness to undergo pre-treatment and on-treatment biopsy.
* Adequate organ function.
* Use of highly effective contraception (females) or male condom plus spermicide (males).
Gender
All
Gender Based
false
Keywords
advanced solid tumors; immunotherapy; OX40; immuno-oncology
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
99 Years
Minimum Age
18 Years
NCT Id
NCT02318394
Org Class
Industry
Org Full Name
MedImmune LLC
Org Study Id
D6060C00001
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Activity of MEDI0562 in Adult Subjects With Selected Advanced Solid Tumors
Primary Outcomes
Outcome Description
The maximum tolerated dose/maximum administered dose will be determined by the number of participants experiencing DLTs. The safety profile will be assessed through number of participants experiencing AEs, SAEs, abnormal laboratory parameters, vital signs and electrocardiogram (ECG) results.
Outcome Measure
Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Outcome Time Frame
From time of informed consent through 12 weeks after last dose of MEDI0562
Secondary Outcomes
Outcome Description
The ORR is defined as the proportion of subjects with confirmed immune related (ir)CR or confirmed irPR
Outcome Time Frame
Estimated to be from time of informed consent up to 5 years
Outcome Measure
Objective response rate (ORR)
Outcome Description
The endpoints for assessment of PK of MEDI0562 include MEDI0562 concentrations in serum at different timepoints after MEDI0562 administration.
Outcome Time Frame
From first dose of MEDI0562 through to 30 days after last dose of investigational product
Outcome Measure
Maximum observed concentration (Cmax), area under the curve (AUC), clearance (CL) and terminal half-life of MEDI0562
Outcome Description
The immunogenicity of MEDI0562 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs)
Outcome Time Frame
From first dose of MEDI0562 through to 30 days after last dose of investigational product
Outcome Measure
Number and percentage of subjects who develop detectable anti-drug antibodies (ADAs)
Outcome Description
The endpoints for assessment of pharmacodynamic activity include induction of proliferation markers in various lymphoctye subsets, immunohistochemistry of tumor biopsies and assessment of programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocyte phenotypic markers
Outcome Time Frame
From time of informed consent through 12 weeks after last dose of investigational product
Outcome Measure
Induction of proliferation markers on various lymphocyte subsets, immunohistochemistry of tumor biopsies and assessment of programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocyte phenotypic markers
Outcome Description
The DCR is defined as the proportion of subjects with irCR, irPR, or irSD (subjects achieving irSD will be included in the DCR if they maintain irSD for ≥8 weeks)
Outcome Time Frame
Estimated to be from time of informed consent up to 5 years
Outcome Measure
Disease control rate (DCR)
Outcome Description
Duration of response will be defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.
Outcome Time Frame
Estimated to be from time of informed consent up to 5 years
Outcome Measure
Duration of response (DoR)
Outcome Description
Progression-free survival will be measured from the start of treatment with MEDI0562 until the first documentation of confirmed immune-related disease progression or death due to any cause, whichever occurs first.
Outcome Time Frame
Estimated to be from time of informed consent up to 5 years
Outcome Measure
Progression-free survival (PFS)
Outcome Description
Overall survival will be determined as the time from the start of treatment with MEDI0562 until death due to any cause.
Outcome Time Frame
Estimated to be from time of informed consent up to 5 years
Outcome Measure
Overall survival (OS)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
99
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sanjay Goel
Investigator Email
sgoel@montefiore.org
Investigator Phone
718-405-8404