A Study in Adult Subjects With Select Advanced Solid Tumors

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02583165
• Collaborator: (none)
• Enrollment: 40
• Locations: 10
• Arm: 1
• Actual Duration (Months): 37.3
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Biological: MEDI1873	Phase 1

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of MEDI1873 (GITR Agonist) in Adult Subjects With Select Advanced Solid Tumors
• Actual Study Start Date: Nov 9, 2015
• Actual Primary Completion Date: Dec 19, 2018
• Actual Study Completion Date: Dec 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Monotherapy arm MEDI1873	Biological: MEDI1873; Subjects will receive MEDI1873 by intravenous administration

Outcome Measures

Primary Outcome Measures

1. 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 months after last dose of MEDI1873]

   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.

Secondary Outcome Measures

1. Objective response rate (ORR) [Estimated to be from time of informed consent up to 4.5 years]

   The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1

2. Disease control rate (DCR) [Estimated to be from time of informed consent up to 4.5 years]

   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

3. Duration of response (DoR) [Estimated to be from time of informed consent up to 4.5 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.

4. Progression-free survival (PFS) [Estimated to be from time of informed consent up to 4.5 years]

   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.

5. Overall survival (OS) [Estimated to be from time of informed consent up to 4.5 years]

   Overall survival will be determined as the time from the start of treatment with MEDI1873 until death due to any cause.

6. Maximum observed concentration (Cmax) of MEDI1873 [From first dose of MEDI1873 through to 30 days after last dose of MEDI1873]

   The endpoint for assessment of PK of MEDI1873 include serum concentrations of MEDI1873 at different timepoints after MEDI1873 administration

7. Number of subjects who develop detectable anti-drug antibodies (ADAs) [From first dose of MEDI1873 through to 12 months after last dose of MEDI1873]

   The immunogenicity of MEDI1873 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs)

8. 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]

   PD biomarkers including changes from baseline levels in various lymphocyte populations

9. Area under the curve (AUC) of MEDI1873 [From first dose of MEDI1873 through to 30 days after last dose of MEDI1873]

   The endpoint for assessment of PK of MEDI1873 include serum concentrations of MEDI1873 at different timepoints after MEDI1873 administration

10. Clearance (CL) of MEDI1873 [From first dose of MEDI1873 through to 30 days after last dose of MEDI1873]

    The endpoint for assessment of PK of MEDI1873 include serum concentrations of MEDI1873 at different timepoints after MEDI1873 administration

11. Terminal half-life of MEDI1873 [From first dose of MEDI1873 through to 30 days after last dose of MEDI1873]

    The endpoint for assessment of PK of MEDI1873 include serum concentrations of MEDI1873 at different timepoints after MEDI1873 administration

12. Percentage of subjects who develop detectable anti-drug antibodies (ADAs) [From first dose of MEDI1873 through to 12 months after last dose of MEDI1873]

    The immunogenicity of MEDI1873 will be assessed by summarizing the percentage of subjects who develop detectable anti-drug antibodies (ADAs)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Phoenix	Arizona	United States	85054
2	Research Site	Scottsdale	Arizona	United States	85258
3	Research Site	Los Angeles	California	United States	90025
4	Research Site	Tampa	Florida	United States	33612
5	Research Site	Rochester	Minnesota	United States	55905
6	Research Site	New York	New York	United States	10032
7	Research Site	Oklahoma City	Oklahoma	United States	73117
8	Research Site	Philadelphia	Pennsylvania	United States	19111
9	Research Site	Nashville	Tennessee	United States	37203
10	Research Site	Houston	Texas	United States	77521

Sponsors and Collaborators

• MedImmune LLC

Investigators

• Study Director: Medimmune LLC, MedImmune LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT02583165
• Other Study ID Numbers: D6150C00001
• First Posted: Oct 22, 2015
• Last Update Posted: Jan 8, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by MedImmune LLC: advanced solid tumors; immunotherapy; immuno-oncology
• Additional relevant MeSH terms: Neoplasms

Study Results

No Results Posted as of Jan 8, 2019