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

• ClinicalTrials.gov Identifier: NCT04592653
• Recruitment Status: Recruiting
• First Posted: October 19, 2020
• Last Update Posted: October 19, 2020
• Sponsor: Alkermes, Inc.
• Information provided by (Responsible Party): Alkermes, Inc.

Tracking Information

• First Submitted Date: August 24, 2020
• First Posted Date: October 19, 2020
• Last Update Posted Date: October 19, 2020
• Actual Study Start Date: September 30, 2020
• Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 12, 2020)

• 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
• 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 ]

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: October 12, 2020)

• 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 ]
• 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) ]
• 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 ]
• 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) ]
• 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) ]
• 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 [ 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
• 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
• 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
• 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
• 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 [ 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumor

Intervention

• Drug: ALKS 4230
  IV infusion over 30 minutes
• Drug: Pembrolizumab
  IV infusion over 30 minutes
  Other Name: Keytruda

Study Arms

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.

Interventions:

• Drug: ALKS 4230
• Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 12, 2020): 36
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2022
• Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04592653
• Other Study ID Numbers: ALKS 4230-003
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Alkermes, Inc.
• Study Sponsor: Alkermes, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Bruce Dezube, MD; Alkermes, Inc.

• PRS Account: Alkermes, Inc.
• Verification Date: October 2020