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A Phase 1 Study of MEDI0562 in Adult Subjects With Selected Advanced Solid Tumors

Phase 1
Completed
Conditions
Advanced Solid Tumors
Interventions
Biological: MEDI0562
Registration Number
NCT02318394
Lead Sponsor
MedImmune LLC
Brief Summary

To evaluate the safety and tolerability 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
56
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Monotherapy ArmMEDI0562MEDI0562 monotherapy
Primary Outcome Measures
NameTimeMethod
Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)From time of informed consent through 12 weeks after last dose of MEDI0562

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.

Secondary Outcome Measures
NameTimeMethod
Duration of response (DoR)Estimated to be from time of informed consent up to 5 years

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.

Number and percentage of subjects who develop detectable anti-drug antibodies (ADAs)From first dose of MEDI0562 through to 30 days after last dose of investigational product

The immunogenicity of MEDI0562 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs)

Disease control rate (DCR)Estimated to be from time of informed consent up to 5 years

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)

Objective response rate (ORR)Estimated to be from time of informed consent up to 5 years

The ORR is defined as the proportion of subjects with confirmed immune related (ir)CR or confirmed irPR

Maximum observed concentration (Cmax), area under the curve (AUC), clearance (CL) and terminal half-life of MEDI0562From first dose of MEDI0562 through to 30 days after last dose of investigational product

The endpoints for assessment of PK of MEDI0562 include MEDI0562 concentrations in serum at different timepoints after MEDI0562 administration.

Progression-free survival (PFS)Estimated to be from time of informed consent up to 5 years

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.

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 markersFrom time of informed consent through 12 weeks after last dose of investigational product

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

Overall survival (OS)Estimated to be from time of informed consent up to 5 years

Overall survival will be determined as the time from the start of treatment with MEDI0562 until death due to any cause.

Trial Locations

Locations (1)

Research Site

🇰🇷

Seoul, Korea, Republic of

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