Clinical Trials /

A Study of ALKS 4230 on the Tumor Microenvironment

NCT04592653

Description:

The primary objective of this study is to evaluate the effects of ALKS 4230 monotherapy on the tumor microenvironment of a variety of advanced, malignant solid tumors.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Cutaneous Melanoma
  • Malignant Solid Tumor
  • Ovarian Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of ALKS 4230 on the Tumor Microenvironment
  • Official Title: Clinical and Immunologic Activity of ALKS 4230 on Tumor Microenvironment in Solid Tumor Patients - ARTISTRY-3

Clinical Trial IDs

  • ORG STUDY ID: ALKS 4230-003
  • NCT ID: NCT04592653

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
ALKS 4230ALKS 4230 + pembrolizumab
PembrolizumabKeytrudaALKS 4230 + pembrolizumab

Purpose

The primary objective of this study is to evaluate the effects of ALKS 4230 monotherapy on the tumor microenvironment of a variety of advanced, malignant solid tumors.

Trial Arms

NameTypeDescriptionInterventions
ALKS 4230 + pembrolizumabExperimentalALKS 4230 will be administered via Intravenous (IV) infusion given daily for 5 consecutive days followed by an off-treatment period. Starting on Cycle 3, Day 1 of each cycle, Pembrolizumab will be administered via IV infusion followed by IV infusion of ALKS 4230.
  • ALKS 4230
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed diagnosis of an advanced
             solid malignancy (cutaneous melanoma, RCC, TNBC, Microsatellite-stable (MSS)
             colorectal cancer, Microsatellite-high (MSI-H) solid tumors [not otherwise specified],
             or ovarian cancer) after treatment failure or intolerance to at least one established,
             indication-specific therapy.

          -  Patients must be willing to provide tumor tissue biopsy and have accessible lesions
             for biopsy.

          -  All patients must provide a baseline biopsy from no more than 3 months prior to
             screening, and at least 4 weeks after completion of last anti-cancer therapy.

          -  Patients must have disease that is measurable by RECIST 1.1.

          -  Patients must demonstrate adequate organ function

          -  Female patients of childbearing potential should have a negative pregnancy test within
             72 hours prior to receiving the first dose of study medication

          -  Patients must agree to follow contraceptive requirements defined in the protocol

          -  Additional criteria may apply

        Exclusion Criteria:

          -  Patient is pregnant or breastfeeding or is planning to become pregnant during the
             study period.

          -  Patients with an active infection or with a fever ≥38.5°C within 3 days of the first
             scheduled day of dosing

          -  Patients with primary CNS malignancy

          -  Patients with active or symptomatic central nervous system metastases unless the
             metastases have been treated by surgery and/or radiation therapy and/or gamma knife,
             the subject has been tapered to a dose of 10 mg of prednisone (or equivalent) or less
             of corticosteroids for at least 2 weeks before the first dose, and the subject is
             neurologically stable. Patients with leptomeningeal disease are excluded.

          -  Patients with hypersensitivity to pembrolizumab, ALKS 4230, or any of their excipients

          -  Patients who have received systemic immunomodulatory agents within 6 weeks prior to
             the first scheduled day of dosing

          -  Patients who have received prior IL-2-based or IL-15-based cytokine therapy at any
             time in the past

          -  Patients who require pharmacologic doses of systemic corticosteroids (greater than 10
             mg of prednisone daily or equivalent); however, topical, ophthalmologic, and
             inhalational steroids are permitted

          -  Patients with an uncontrollable bleeding disorder

          -  Patients known to be positive for human immunodeficiency virus and/or history of
             hepatitis B, or C infections or is known to be positive for hepatitis B antigen
             (HBsAg)/hepatitis B virus (HBV) DNA or hepatitis C antibody (Hep C Ab) or RNA.

          -  Patients with any other concurrent uncontrolled illness, including mental illness or
             substance abuse, which may interfere with the ability of the subject to cooperate and
             participate in the study.

          -  Additional criteria may apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Changes in density (cell counts per mm2) of immune cell (including total T cells, CD8+ T cells, CD56+ cells and Treg cells)
Time Frame:From the time of the Patient's pre-treatment biopsy to the time of the Patient's on-treatment biopsy
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Proportion of subjects with objective evidence of Complete Response (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
Safety Issue:
Description:
Measure:Duration of response in subjects with Complete Response (CR)/immune CR (iCR)
Time Frame:Time from the first documentation of complete response, measured approximately every 6 weeks, to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months)
Safety Issue:
Description:
Measure:Proportion of subjects with objective evidence of Partial Response (PR)/immune PR (iPR)
Time Frame:From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months
Safety Issue:
Description:
Measure:Duration of response in subjects with Partial Response (PR)/immune PR (iPR)
Time Frame:Time from the first documentation of partial response, measured approximately every 6 weeks, to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months)
Safety Issue:
Description:
Measure:Incidence of drug-related Adverse Events
Time Frame:Time from first dose of study drug to the end of study (estimated up to 24 months)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Serum concentrations of ALKS 4230
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
Safety Issue:
Description:Concentration data will be summarized by dose level
Measure:Serum will be assayed for the presence of anti-ALKS 4230 antibodies
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
Safety Issue:
Description:Results will be summarized by dose level
Measure:Changes in absolute cell numbers (including total T cells, CD8+ T cells, NK cells and Treg cells)
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
Safety Issue:
Description: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
Measure:Changes in ratios (including T/Treg, CD8+/Treg, NK/Treg) between pretreatment and on treatment
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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description:
Measure:Changes in absolute numbers of circulating leukocytes
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
Safety Issue:
Description: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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Alkermes, Inc.

Trial Keywords

  • Alkermes
  • IL-2
  • Interleukin-2
  • Oncology
  • Immuno-oncology
  • Cytokine
  • Pembrolizumab
  • Keytruda
  • PD-L1
  • Solid tumors
  • Immunotherapy

Last Updated

October 19, 2020