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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 Subjects 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 25, 2020
Sponsor:
Information provided by (Responsible Party):
Alkermes, Inc.

Tracking Information
First Submitted Date  ICMJE February 25, 2019
First Posted Date  ICMJE March 4, 2019
Last Update Posted Date August 25, 2020
Actual Study Start Date  ICMJE February 26, 2019
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2020)
  • 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
  • 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 ]
    Includes AEs that are both serious and drug-related
  • Clinical Activity of combination treatment with ALKS 4230 and pembrolizumab in each Part B tumor type. [ Time Frame: From time 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 and photographic images
Original Primary Outcome Measures  ICMJE
 (submitted: March 1, 2019)
  • 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
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 7, 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 ]
    Overall response rate (ORR) will be based on investigator review of radiographic or photographic images
  • 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 ]
    ORR will be based on investigator review of radiographic or photographic images
  • Duration of response in subjects with 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) ]
    CR/iCR duration
  • Duration of response in subjects with PR/iPR [ 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) ]
    PR/iPR duration
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2019)
  • 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
  • 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
  • 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) ]
  • 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) ]
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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 Subjects With Select Advanced or Metastatic Solid Tumors (ARTISTRY-2)
Official Title  ICMJE A Phase 1/2 Study of ALKS 4230 Administered Subcutaneously as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors - ARTISTRY-2 (001)
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: ALKS 4230
    Administered via SC injection once every 7 days or once every 21 days at escalating doses
    Intervention: Biological: ALKS 4230
  • 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
    Interventions:
    • Biological: ALKS 4230
    • Biological: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 7, 2020)
319
Original Estimated Enrollment  ICMJE
 (submitted: March 1, 2019)
230
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jennifer Skinner 303-704-6798 Jennifer.skinner@syneoshealth.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03861793
Other Study ID Numbers  ICMJE ALKS 4230-001
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  ICMJE
Plan to Share IPD: No
Plan Description: At this time, IPD sharing has not been defined and/or decided if it will be shared.
Responsible Party Alkermes, Inc.
Study Sponsor  ICMJE Alkermes, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Alkermes Medical Director Alkermes, Inc.
PRS Account Alkermes, Inc.
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP