Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Less Frequent IV Dosing & Tumor Microenvironment (TME) Study of Nemvaleukin Alfa (ALKS 4230) Monotherapy and in Combination With Pembrolizumab (ARTISTRY-3) (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 : May 11, 2022
Sponsor:
Information provided by (Responsible Party):
Alkermes, Inc.

Brief Summary:
The study will be conducted in 2 cohorts. A single-center design for the tumor microenvironment (TME) cohort (Cohort 1), and a multicenter design for the less frequent intravenous (IV) dosing cohort (Cohort 2).

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Biological: Nemvaleukin alfa Biological: Pembrolizumab Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical and Immunologic Activity of Nemvaleukin Alfa With Less Frequent IV Dosing Schedule as Monotherapy and in Combination With Pembrolizumab and Impact on Tumor Microenvironment in Solid Tumor Patients - ARTISTRY-3
Actual Study Start Date : September 30, 2020
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1: Tumor Microenvironment (TME) Nemvaleukin and Pembrolizumab
Nemvaleukin 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 nemvaleukin
Biological: Nemvaleukin alfa
IV infusion over 30 minutes
Other Name: ALKS 4230

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

Experimental: Cohort 2 Part A: Less Frequent IV Dosing Nemvaleukin Biological: Nemvaleukin alfa
IV infusion over 30 minutes
Other Name: ALKS 4230

Experimental: Cohort 2 Part B: Less Frequent IV Dosing Nemvaleukin and Pembrolizumab Biological: Nemvaleukin alfa
IV infusion over 30 minutes
Other Name: ALKS 4230

Biological: 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 ]
  3. Incidence of dose-limiting toxicity (DLT) [ Time Frame: From the first dose through end of dose-limiting toxicity observation period (up to 24 months) ]

Secondary Outcome Measures :
  1. Proportion of subjects with objective evidence of Complete or Partial Response [(CR)/immune CR (iCR) or (PR) immune PR (iPR)](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 or Partial Response [(CR)/immune CR (iCR) or (PR) immune PR (iPR)] [ Time Frame: Time from the first documentation of complete response or partial response to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months) ]
  3. Incidence of Adverse Events [ Time Frame: Time from first dose of study drug to the end of study (estimated up to 24 months) ]
  4. 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) ]
  5. 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) ]
  6. 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

  7. 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

  8. 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

  9. 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

  10. 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 ]
  11. 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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 tumor type of cutaneous melanoma, RCC, TNBC, MSS colorectal cancer, MSI-H solid tumors (NOS), or ovarian cancer with at least 1 accessible lesion for biopsy (Cohort 1 TME)
  • Patients must have histologically or cytologically confirmed epithelial tumor of the fallopian tube, peritoneum, or ovaries, cervical cancer, endometrial cancer, non-small cell lung adenocarcinoma, small cell lung cancer, gastric and gastroesophageal junction adenocarcinoma, esophageal cancer (squamous and adeno cell type), pancreatic cancer, biliary tract tumor (including intra- and extrahepatic cholangiocarcinoma, gall bladder, ampullary type), cutaneous melanoma, mucosal melanoma, head and neck squamous cell carcinoma, or metastatic or advanced breast cancer after treatment failure or intolerance of 1 to 3 established indication specific therapies (Cohort 2)
  • Patient must have received 1 to 3 prior FDA-approved targeted therapies, failure of adjuvant and neoadjuvant therapy is considered 1 line of treatment
  • All patients' baseline biopsies must be taken no more than 3 months before Screening and at least 4 weeks after completion of last antineoplastic therapy
  • Patients must have at least 1 lesion that qualifies as a target lesion
  • Patients must have adequate hematologic reserve
  • Patients must have adequate hepatic and renal function
  • For Cohort 1 (TME) and Part A of Cohort 2 (less frequent IV dosing), treatment with prior immunotherapy is permitted unless the patient has previously experienced grade ≥3 autoimmune toxicity or drug-related toxicity requiring discontinuation. Patients in Part B of Cohort 2 (less frequent IV dosing) who received prior anti-PD-(L)1 for at least 3 months may enroll if they had a response of stable disease or better
  • Women of childbearing potential (WOCBP) must have a negative pregnancy test
  • Additional criteria may apply

Exclusion Criteria:

  • Patients with active or symptomatic central nervous system metastases
  • Patients who require pharmacologic doses of systemic corticosteroids (greater than 10 mg of prednisone daily or equivalent)
  • Patients known to be positive for HIV 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 a known additional malignancy within 2 years of the start of Screening
  • Patients who have received radiotherapy within the last 4 weeks before start of study treatment
  • Patients who have received systemic immunomodulatory agents within 4 weeks or 5 half lives, whichever is shorter, before Cycle 1 Day 1,
  • Patients who have received prior IL-2-based or IL-15-based soluble protein therapy at any time in the past are excluded
  • 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
Layout table for location contacts
Contact: Director Global Clinical Services 888-235-8008 (US Only) clinicaltrials@alkermes.com
Contact: Director Global Clinical Services 1-571-599-2702 (Global) clinicaltrials@alkermes.com

Locations
Layout table for location information
United States, Michigan
Alkermes Investigator Site Recruiting
Grand Rapids, Michigan, United States, 49546
United States, Texas
MD Anderson Cancer Center Active, not recruiting
Houston, Texas, United States, 77030
United States, Utah
Alkermes Investigator Site Recruiting
West Valley City, Utah, United States, 84119
Sponsors and Collaborators
Alkermes, Inc.
Investigators
Layout table for investigator information
Study Director: Rita Dalal, MD Alkermes, Inc.
Layout table for additonal information
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: May 11, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
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
Nemvaleukin
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents