Status:

COMPLETED

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

Lead Sponsor:

MedImmune LLC

Conditions:

Recurrent or Metastatic Solid Tumors

Eligibility:

All Genders

18-99 years

Phase:

PHASE1

Brief Summary

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

Detailed Description

This is a Phase 1, multicenter, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics, and antitumor activity o...

Eligibility Criteria

Inclusion

  • 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

Exclusion

  • 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
  • True positive test results for human immunodeficiency virus (HIV) or hepatitis B or C
  • Receipt of live, attenuated vaccine within 28 days prior to the first dose of investigational products )
  • Pregnant or breastfeeding women
  • Major surgery (as defined by the investigator) within 4 weeks prior to first dose of MEDI6383 or still recovering from prior surgery. Local surgery of isolated lesions for palliative intent is acceptable
  • Other invasive malignancy within 2 years
  • \-

Key Trial Info

Start Date :

September 15 2014

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

July 3 2017

Estimated Enrollment :

39 Patients enrolled

Trial Details

Trial ID

NCT02221960

Start Date

September 15 2014

End Date

July 3 2017

Last Update

March 13 2019

Active Locations (8)

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Page 1 of 2 (8 locations)

1

Research Site

La Jolla, California, United States, 92093

2

Research Site

New Haven, Connecticut, United States, 06520

3

Research Site

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

4

Research Site

Chicago, Illinois, United States, 60611