The study will be conducted in 2 cohorts. A single-center design for the tumor microenvironment (TME) cohort (Cohort 1), and a multicenter design for the less frequent intravenous (IV) dosing cohort (Cohort 2).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
78
IV infusion over 30 minutes
IV infusion over 30 minutes
START Midwest
Grand Rapids, Michigan, United States
MD Anderson Cancer Center
Houston, Texas, United States
START Mountain
West Valley City, Utah, United States
NEXT Virginia
Fairfax, Virginia, United States
Changes in density (cell counts per mm2) of immune cell (including total T cells, CD8+ T cells, CD56+ cells and Treg cells)
Changes in density (cell counts per mm2) of immune cell (including total T cells, CD8+ T cells, CD56+ cells and Treg cells) based on immunohistochemistry (IHC) and/or immunofluorescence (IF) in the TME between pretreatment and on-treatment (Cycle 2 Day 8) paired tumor biopsies
Time frame: From the time of the Patient's pre-treatment biopsy to the time of the Patient's on-treatment biopsy
Changes in ratios (including T/Treg, CD8+/Treg, CD56+/Treg) based on immunohistochemistry (IHC) and/or immunofluorescence (IF) in the TME between pretreatment and on-treatment (Cycle 2 Day 8) paired tumor biopsies
Time frame: From the time of the Patient's pre-treatment biopsy to the time of the Patient's on-treatment biopsy
Incidence of dose-limiting toxicity (DLT)
Time frame: From the first dose through end of dose-limiting toxicity observation period (up to 24 months)
Proportion of subjects with objective evidence of Complete or Partial Response [(CR)/immune CR (iCR) or (PR) immune PR (iPR)](CR)/immune CR (iCR)
Time frame: From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months
Duration of response in subjects with Complete or Partial Response [(CR)/immune CR (iCR) or (PR) immune PR (iPR)]
Time frame: Time from the first documentation of complete response or partial response to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months)
Incidence of Adverse Events
Time frame: Time from first dose of study drug to the end of study (estimated up to 24 months)
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Hospital Clinico San Carlos
Madrid, Spain
CIOCC HM Sanchinarro
Madrid, Spain
Incidence of drug-related Serious Adverse Events
Time frame: Time from first dose of study drug to the end of study (estimated up to 24 months)
Incidence of drug-related Adverse Events leading to discontinuation
Time frame: Time from first dose of study drug to the end of study (estimated up to 24 months)
Serum concentrations of ALKS 4230
Concentration data will be summarized by dose level
Time frame: From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months
Serum will be assayed for the presence of anti-ALKS 4230 antibodies
Results will be summarized by dose level
Time frame: From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months
Changes in absolute cell numbers (including total T cells, CD8+ T cells, NK cells and Treg cells)
Changes in absolute cell numbers (including total T cells, CD8+ T cells, NK cells and Treg cells) between pretreatment and on-treatment serial peripheral blood samples obtained from patients being treated with ALKS 4230 monotherapy and with the combination of ALKS 4230 plus pembrolizumab
Time frame: From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months
Changes in ratios (including T/Treg, CD8+/Treg, NK/Treg) between pretreatment and on treatment
Changes in ratios (including T/Treg, CD8+/Treg, NK/Treg) between pretreatment and on-treatment serial peripheral blood samples obtained from patients being treated with ALKS 4230 monotherapy and with the combination of ALKS 4230 plus pembrolizumab
Time frame: From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months
Serum concentrations of proinflammatory cytokines, including IFNγ, TNF-α, IL-1B, IL-6, IL-10, will be assessed using a multiplex method from initiation of therapy
Time frame: From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months
Changes in absolute numbers of circulating leukocytes
Changes in absolute numbers of circulating leukocytes between pretreatment and on-treatment serial peripheral blood samples obtained from patients being treated with ALKS 4230 monotherapy and with the combination of ALKS 4230 plus pembrolizumab
Time frame: From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months