A Study in Adult Subjects With Select Advanced Solid Tumors

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of MEDI1873 in adult subjects with selected advanced solid tumors.

Detailed Description
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This is a first-time-in-human, Phase 1, multicenter, open-label, single-arm dose-escalation study of MEDI1873 to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics and anti-tumor activity in adult subjects with advanced solid tumor malignancies

Official Title
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A Phase 1 Study of MEDI1873 (GITR Agonist) in Adult Subjects With Select Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Biological: MEDI1873


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects must consent to provide archived tumor specimen Subjects must have histologically or cytologically confirmed advanced solid tumor for recurrent or metastatic disease. At the time of Day 1 of the study, subjects with central nervous system (CNS) metastases must have been treated and must be asymptomatic Willingness to provide pretreatment and on-treatment biopsies. Adequate organ function Females of childbearing potential and nonsterilized males who are sexually active must use effective methods of contraception Exclusion Criteria: Known allergic reaction to any component of MEDI1873 Concurrent enrollment in another clinical study, unless it is an observational clinical study or the follow-up period of an interventional study Receipt of any anticancer therapy within 4 weeks prior to the first dose of MEDI1873; in the case of mAbs, 6 weeks prior to the first dose of MEDI1873 Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment. Receipt of live, attenuated vaccine within 28 days prior to the first dose of investigational product 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy arm<br>MEDI1873 | Biological: MEDI1873<br>* Subjects will receive MEDI1873 by intravenous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) | The maximum tolerated dose (MTD)/highest protocol-defined dose level in the absence of establishing an MTD will be determined by the number of participants experiencing DLTs. The safety profile will be assessed through number of participants experiencing AEs, SAEs, DLTs, abnormal laboratory parameters, vital signs and electrocardiogram (ECG) results. | From time of informed consent through 12 months after last dose of MEDI1873 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1 | Estimated to be from time of informed consent up to 4.5 years | 
| Disease control rate (DCR) | The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1 | Estimated to be from time of informed consent up to 4.5 years | 
| Duration of response (DoR) | 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. | Estimated to be from time of informed consent up to 4.5 years | 
| Progression-free survival (PFS) | Progression-free survival will be measured from the start of treatment with MEDI1873 until the first documentation of disease progression or death due to any cause, whichever occurs first. | Estimated to be from time of informed consent up to 4.5 years | 
| Overall survival (OS) | Overall survival will be determined as the time from the start of treatment with MEDI1873 until death due to any cause. | Estimated to be from time of informed consent up to 4.5 years | 
| Maximum observed concentration (Cmax) of MEDI1873 | The endpoint for assessment of PK of MEDI1873 include serum concentrations of MEDI1873 at different timepoints after MEDI1873 administration | From first dose of MEDI1873 through to 30 days after last dose of MEDI1873 | 
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | The immunogenicity of MEDI1873 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs) | From first dose of MEDI1873 through to 12 months after last dose of MEDI1873 | 
| PD biomarkers including changes from baseline levels in various lymphocyte populations | PD biomarkers including changes from baseline levels in various lymphocyte populations | From time of informed consent through to disease progression, assessed up to 4.5 years | 
| Area under the curve (AUC) of MEDI1873 | The endpoint for assessment of PK of MEDI1873 include serum concentrations of MEDI1873 at different timepoints after MEDI1873 administration | From first dose of MEDI1873 through to 30 days after last dose of MEDI1873 | 
| Clearance (CL) of MEDI1873 | The endpoint for assessment of PK of MEDI1873 include serum concentrations of MEDI1873 at different timepoints after MEDI1873 administration | From first dose of MEDI1873 through to 30 days after last dose of MEDI1873 | 
| Terminal half-life of MEDI1873 | The endpoint for assessment of PK of MEDI1873 include serum concentrations of MEDI1873 at different timepoints after MEDI1873 administration | From first dose of MEDI1873 through to 30 days after last dose of MEDI1873 | 
| Percentage of subjects who develop detectable anti-drug antibodies (ADAs) | The immunogenicity of MEDI1873 will be assessed by summarizing the percentage of subjects who develop detectable anti-drug antibodies (ADAs) | From first dose of MEDI1873 through to 12 months after last dose of MEDI1873 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced solid tumors, immunotherapy, immuno-oncology