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A Study of ALKS 4230 on the Tumor Microenvironment (ARTISTRY-3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04592653
Recruitment Status : Recruiting
First Posted : October 19, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Alkermes, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: ALKS 4230 Drug: Pembrolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical and Immunologic Activity of ALKS 4230 on Tumor Microenvironment in Solid Tumor Patients - ARTISTRY-3
Actual Study Start Date : September 30, 2020
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ALKS 4230 + pembrolizumab
ALKS 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.
Drug: ALKS 4230
IV infusion over 30 minutes

Drug: Pembrolizumab
IV infusion over 30 minutes
Other Name: Keytruda




Primary Outcome Measures :
  1. 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 ]
    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

  2. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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) ]
  3. 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 ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. 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) ]
  8. 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 ]
    Concentration data will be summarized by dose level

  9. 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 ]
    Results will be summarized by dose level

  10. 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 ]
    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

  11. 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 ]
    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

  12. 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 ]
  13. 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 ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04592653


Contacts
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Contact: James Corkery 781-296-8638 James.Corkery@alkermes.com

Locations
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United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Alkermes, Inc.
Investigators
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Study Director: Bruce Dezube, MD Alkermes, Inc.
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Responsible Party: Alkermes, Inc.
ClinicalTrials.gov Identifier: NCT04592653    
Other Study ID Numbers: ALKS 4230-003
First Posted: October 19, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alkermes, Inc.:
Alkermes
IL-2
Interleukin-2
Oncology
Immuno-oncology
Cytokine
Pembrolizumab
Keytruda
PD-L1
Solid tumors
Immunotherapy
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents