Multiple Ascending Dose (MDX1105-01)

NCT00729664 — Phase 1, Completed, 281 participants, Bristol-Myers Squibb

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A Phase 1, Multidose Study of BMS-936559 (MDX-1105) Administered Every 14 Days in Subjects With Selected Advanced or Recurrent Solid Tumors

Registry	NCT00729664, acronym Anti-PDL1
Status	Completed
Phase	Phase 1
Study type	Interventional; non randomized, parallel, masking: none, treatment
Enrollment	281 (Actual)
Sponsor	Bristol-Myers Squibb (Industry)
Conditions	Cancer, Multiple Indications
Interventions	Anti-PDL-1 antibody (Biological)
Dates	start 2009-02-01, primary completion 2015-07-01, completion 2015-07-01, first posted 2008-08-07, last updated 2015-09-07
Locations	11 sites in United States

-Summary

Collection of survival data, evaluation of PDL-1 expression in tumors, and evaluation of PD-L1 receptor occupancy in peripheral blood has been added.

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+Detailed description

This is an open label, multicenter, dose escalation and multidose study of MDX-11-5, a fully human monoclonal IgG4 antibody targeting the Programed Death-Ligand 1 (PD-L1).

The study will consist of 3 periods: Screening (up to 28 days), Treatment (up to 16 six-week cycles), and Follow-up (up to 6 months).

+Arms and interventions

Arm	Type	Interventions	Description
Anti-PDL-1 antibody (Arm 1)	Experimental	Biological: Anti-PDL-1 antibody	BMS-936559 (MDX-1105)
Anti-PDL-1 antibody (Arm 2)	Experimental	Biological: Anti-PDL-1 antibody	BMS-936559 (MDX-1105)
Anti-PDL-1 antibody (Arm 3)	Experimental	Biological: Anti-PDL-1 antibody	BMS-936559 (MDX-1105)
Anti-PDL-1 antibody (Arm 4)	Experimental	Biological: Anti-PDL-1 antibody	BMS-936559 (MDX-1105)
Anti-PDL-1 antibody (Arm 5)	Experimental	Biological: Anti-PDL-1 antibody	BMS-936559 (MDX-1105)

Anti-PDL-1 antibody (Biological), also known as BMS-936559, MDX 1105: Solution, Intravenous, 0.1 mg/kg, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles/48 doses depending on response
Anti-PDL-1 antibody (Biological), also known as BMS-936559, MDX 1105: Solution, Intravenous, 0.3 mg/kg, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles/48 doses depending on response
Anti-PDL-1 antibody (Biological), also known as BMS-936559, MDX 1105: Solution, Intravenous, 1 mg/kg, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles/48 doses depending on response
Anti-PDL-1 antibody (Biological), also known as BMS-936559, MDX 1105: Solution, Intravenous, 3 mg/kg, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles/48 doses depending on response
Anti-PDL-1 antibody (Biological), also known as BMS-936559, MDX 1105: Solution, Intravenous, 10 mg/kg, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles/48 doses depending on response

+Outcome measures

Primary outcomes

Safety, maximum tolerated dose (MTD) and dose-limiting toxicity(DLT)of MDX-1105 [Weekly]
Safety, maximum tolerated dose (MTD) and dose-limiting toxicity(DLT)of MDX-1105 [Bi-weekly]

Secondary outcomes

Preliminary efficacy in solid tumors on the basis of objective responses [Day 42]

+Eligibility

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
* The malignancies include relapsed/refractory renal cell carcinoma, non-small cell lung cancer, colorectal adenocarcinoma, malignant melanoma, advanced/metastatic epithelial ovarian cancer, gastric cancer, pancreatic cancer and breastcancer
* Must have measurable disease

Exclusion Criteria:

* Prior therapy with an anti-PD 1, anti-PDL 1, or anti-Cytotoxic T-Lymphocyte Antigen 4 antibody (or any other agents that target T-cell co-stimulation)

+Locations (11)

Facility	City	Country
The Angeles Clinic & Research Institute	Los Angeles, California	United States
Emory University	Atlanta, Georgia	United States
University Of Chicago	Chicago, Illinois	United States
Johns Hopkins University	Baltimore, Maryland	United States
Mayo Clinic	Rochester, Minnesota	United States
Roswell Park Cancer Institute	Buffalo, New York	United States
University Of Cincinnati	Cincinnati, Ohio	United States
Ohio State University	Columbus, Ohio	United States
Oncology Consultants, Pa	Houston, Texas	United States
The University Of Texas	Houston, Texas	United States
Fred Hutchinson Cancer Center	Seattle, Washington	United States

+Publications

Results publication: Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2. PMID 22658128

+Investigators

Bristol-Myers Squibb, Study director, Bristol-Myers Squibb