A Phase 1 Study to Evaluate MEDI6383 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors

NCT02221960 | Completed Phase 1

• 1 other identifier: D6050C00001
• Study Type: interventional
• Target: 39
• Locations: 2 countries
• Sites: 8

Brief Summary

To evaluate MEDI6383 when given alone or together with MEDI4736 in adult subjects with recurrent or metastatic solid tumors.

Conditions

Recurrent or Metastatic Solid Tumors

Keywords

Recurrent or metastatic solid tumors, MEDI6383, OX40

Outcome Measures

Primary Outcomes (1)

• Safety

  Primary endpoint will be the number (%) of subjects with adverse events and serious adverse events.

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

Secondary Outcomes (4)

• Preliminary Antitumor Activity

  Duration of Study

• Pharmacokinetics of MEDI6383 or MEDI6383/MEDI4736

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

• Biomarker Activity

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

• Immunogenicity

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

Study Arms (2)

Monotherapy Arm

EXPERIMENTAL

MEDI6383

Biological: MEDI6383

Combination Arm

EXPERIMENTAL

MEDI6383 and MEDI4736

Biological: MEDI6383 and MEDI4736

Interventions

MEDI6383 BIOLOGICAL

Subjects will receive MEDI6383 until disease progression or adverse event.

Monotherapy Arm

MEDI6383 and MEDI4736 BIOLOGICAL

Subjects will recieve MEDI6383 and MEDI4736 until disease progression or adverse event.

Combination Arm

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects; age ≥ 18
• Written informed consent must be obtained
• Subjects must meet the following criteria:
• Have recurrent or metastatic solid tumors
• Must have received and have progressed, are refractory, or are intolerant to standard therapy appropriate for the specific tumor type. Subjects should not have received more than 5 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies
• Subjects must have at least 1 lesion
• Subjects must consent to provide archived tumor specimens and / or tumor biopsy for correlative biomarker studies.
• Eastern Cooperative Oncology Group performance score of 0 or 1
• In the opinion of the invesgator likely to complete ≥ 8 weeks of treatment.
• Adequate organ function as determined by:
• i. Absolute neutrophil count ≥ 1.5 x 109/L (1,500/mm3) ii.Platelet count ≥ 100 x 109/L (100,000/mm3) iii.Hemoglobin ≥ 9.0 g/dL within first 2 weeks prior to first dose of investigational product iv.Calculated creatinine clearance\* (CrCl) or 24 hour urine CrCl \> 50 mL/min v.Total bilirubin ≤ 1.5× ULN; for subjects with documented/suspected Gilbert's disease, bilirubin ≤ 3× ULN vi.Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5× ULN vii.Serum Electrolytes within normal limits
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 methods of highly effective contraception from screening, and must agree to continue using such precautions for 90 days after the final dose of investigational product; 10) Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1 through 90 days after receipt of the final dose of investigational product

You may not qualify if:

• Prior treatment with TNFRSF agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR) .
• Subjects who have received prior therapy with regimens containing CTLA-4, PDL-1, or PD-1 antagonists are NOT permitted to enroll unless all of the following apply:
• Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
• All AEs while receiving prior immunotherapy must have resolved to ≤ Grade 1 or baseline prior to screening for this study.
• Must not have experienced a ≥ Grade 3 AE or neurologic or ocular AE of any grade while receiving prior immunotherapy
• History of severe allergic reactions to any unknown allergens or any components of the study drug formulations
• Active or prior documented autoimmune disease within the past 2 years.
• Untreated central nervous system metastatic disease l
• Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study
• Receipt of anticancer therapy within 28 days prior to the first dose of Investigational Product
• Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment.
• Unresolved toxicities from prior anticancer therapy
• Systemic anticoagulation or daily aspirin dose exceeding 325 mg per day
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI6383. )
• History of primary immunodeficiency, solid organ transplantation, or tuberculosis

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (8)

Research Site

La Jolla, California, 92093, United States

Location

Research Site

New Haven, Connecticut, 06520, United States

Location

Research Site

Washington D.C., District of Columbia, 20007, United States

Location

Research Site

Chicago, Illinois, 60611, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Portland, Oregon, 97213, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Parkville, 3052, Australia

Location

MeSH Terms

Conditions

Recurrence

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Medimmune Medimmune

  MedImmune LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2014
• First Posted: August 21, 2014
• Study Start: September 15, 2014
• Primary Completion: July 3, 2017
• Study Completion: July 3, 2017
• Last Updated: March 13, 2019

Record last verified: 2019-03

Locations

US (7); AU (1)