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A Dose Escalation and Cohort Expansion Study of Subcutaneously-Administered Cytokine (ALKS 4230) as a Single Agent and in Combination With Anti-PD-1 Antibody (Pembrolizumab) in Patients With Select Advanced or Metastatic Solid Tumors (ARTISTRY-2)

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ClinicalTrials.gov Identifier: NCT03861793
Recruitment Status : Recruiting
First Posted : March 4, 2019
Last Update Posted : August 22, 2019
Sponsor:
Information provided by (Responsible Party):
Alkermes, Inc.

Brief Summary:
This study will characterize the safety and tolerability and identify the recommended Phase 2 dose (RP2D) of subcutaneous (SC) ALKS 4230 as monotherapy and in combination with pembrolizumab.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Biological: ALKS 4230 Biological: Pembrolizumab Phase 1

Detailed Description:
This study will evaluate ALKS 4230 administered SC as lead-in monotherapy and in combination with pembrolizumab in subjects with advanced solid tumors.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of ALKS 4230 Administered Subcutaneously as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors (ARTISTRY-2)
Actual Study Start Date : February 26, 2019
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ALKS 4230
Administered via SC injection once every 7 days or once every 21 days at escalating doses
Biological: ALKS 4230
SC injection administered in the back of the arm or the abdomen

Experimental: ALKS 4230 + pembrolizumab
ALKS 4230 will be administered via SC injection once every 21 days at escalating doses or at the recommended phase 2 dose; pembrolizumab will be administered as an intravenous infusion given over 30 minutes; the dose level for pembrolizumab will be 200 mg per the approved label
Biological: ALKS 4230
SC injection administered in the back of the arm or the abdomen

Biological: Pembrolizumab
Administered as an intravenous (IV) infusion over 30 minutes
Other Name: Keytruda




Primary Outcome Measures :
  1. Incidence of Adverse Events (AEs), and identify the RP2D of ALKS 4230 in Part A [ Time Frame: From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months ]
    Includes AEs that are both serious and drug-related

  2. Number of subjects experiencing AEs that are both serious and drug-related in Part B [ Time Frame: From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months ]

Secondary Outcome Measures :
  1. Proportion of subjects with objective evidence of Complete Response (CR) [ Time Frame: From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months ]
    Overall response rate (ORR) will be based on investigator review of radiographic or photographic images

  2. Proportion of subjects with objective evidence of Partial Response (PR) [ Time Frame: From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months ]
    ORR will be based on investigator review of radiographic or photographic images

  3. Duration of response in subjects with CR [ 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) ]
  4. Duration of response in subjects with PR [ 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) ]
  5. Non-progression for Part B [ Time Frame: Assessed up to 24 months ]
    Time from first dose of SC ALKS 4230 to the time of progression or death

  6. Overall survival for Part B [ Time Frame: Assessed up to 24 months ]
    Time from first dose of SC ALKS 4230 to the time of death

  7. Serum concentrations of ALKS 4230 will be determined at various time points [ Time Frame: From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months ]
    Concentration vs time and standard pharmacokinetic (PK) parameters will be summarized by dose level

  8. 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 21 days), assessed up to 24 months ]
    Results will be summarized by dose level

  9. Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points [ Time Frame: From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months ]
    Results will be summarized by dose level

  10. Serum concentrations of proinflammatory cytokines will be assessed using a multiplex method at various time points [ Time Frame: From time of initiation of therapy until the last treatment cycle (each cycle is 21 days), assessed up to 24 months ]
    Results will be summarized by dose level



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:

  • For Part A the subject has histological or cytological evidence of a solid tumor. For Part B the subject must have 1 of the unspecified adult solid tumor types defined in the protocol
  • Record of programmed cell death ligand 1 protein expression status, or availability of fresh or archival tumor tissue for cellular characterization and PD-L1 status
  • Subjects must have adequate liver function
  • Subjects must have adequate kidney function
  • Subjects must be recovered from the effects of any prior chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy or surgery
  • Subjects who have received radiation therapy must wait at least 4 weeks after their last radiation treatment before enrollment into the study
  • Females of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and on Day 1 before the first dose is administered
  • Subject will agree to follow contraceptive requirements defined in the protocol
  • Additional criteria may apply

Exclusion Criteria:

  • Subject is currently pregnant, planning to become pregnant, or breastfeeding
  • Subjects with an active infection or with a fever ≥ 38.5°C within 3 days of the first scheduled day of dosing for Cycle 1
  • Subjects with active or symptomatic central nervous system metastases are excluded. Subjects with central nervous system metastases are eligible for the study if the metastases have been treated by surgery and/or radiation therapy, the subject is off corticosteroids for at least 2 weeks, and the subject is neurologically stable
  • Subjects with known hypersensitivity to any components of ALKS 4230 or to pembrolizumab or any of its excipients
  • Subjects who require pharmacologic doses of steroids; replacement doses, topical, ophthalmologic, and inhalational steroids are permitted
  • Subjects who developed autoimmune disorders while on prior immunotherapy, including pneumonitis, nephritis, and/or neuropathy
  • Subjects with any other concurrent uncontrolled illness, including mental illness or substance abuse, which may interfere with the ability of the subjects to cooperate and participate in the study
  • The subject is known to be positive for human immunodeficiency virus (HIV), hepatitis B or C, or active tuberculosis, or has a known history of tuberculosis
  • 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): NCT03861793


Contacts
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Contact: Melanie Owen 513-763-1937 Melanie.owen@syneoshealth.com

Locations
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United States, Georgia
Alkermes Investigational Site Recruiting
Atlanta, Georgia, United States, 30322
United States, North Carolina
Alkermes Investigational Site Recruiting
Huntersville, North Carolina, United States, 28078
Sponsors and Collaborators
Alkermes, Inc.
Investigators
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Study Director: Alkermes Medical Director Alkermes, Inc.

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Responsible Party: Alkermes, Inc.
ClinicalTrials.gov Identifier: NCT03861793     History of Changes
Other Study ID Numbers: ALKS 4230-001
First Posted: March 4, 2019    Key Record Dates
Last Update Posted: August 22, 2019
Last Verified: August 2019
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
ALKS 4230
Pembrolizumab
Keytruda
PD-L1
Solid tumors
Immunotherapy
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents