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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)

NCT03861793

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: ALKS 4230-001
  • NCT ID: NCT03861793

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
ALKS 4230ALKS 4230
PembrolizumabKeytrudaALKS 4230 + pembrolizumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
ALKS 4230ExperimentalAdministered via SC injection once every 7 days or once every 21 days at escalating doses
  • ALKS 4230
ALKS 4230 + pembrolizumabExperimentalALKS 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
  • ALKS 4230
  • Pembrolizumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Includes AEs that are both serious and drug-related

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Overall response rate (ORR) will be based on investigator review of radiographic or photographic images
Measure: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
Safety Issue:
Description:ORR will be based on investigator review of radiographic or photographic images
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Non-progression for Part B
Time Frame:Assessed up to 24 months
Safety Issue:
Description:Time from first dose of SC ALKS 4230 to the time of progression or death
Measure:Overall survival for Part B
Time Frame:Assessed up to 24 months
Safety Issue:
Description:Time from first dose of SC ALKS 4230 to the time of death
Measure: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
Safety Issue:
Description:Concentration vs time and standard pharmacokinetic (PK) parameters 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 21 days), assessed up to 24 months
Safety Issue:
Description:Results will be summarized by dose level
Measure: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
Safety Issue:
Description:Results will be summarized by dose level
Measure: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
Safety Issue:
Description:Results will be summarized by dose level

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Alkermes, Inc.

Trial Keywords

  • Alkermes
  • IL-2
  • Interleukin-2
  • Oncology
  • Immuno-oncology
  • Cytokine
  • ALKS 4230
  • Pembrolizumab
  • Keytruda
  • PD-L1
  • Solid tumors
  • Immunotherapy

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