Less Frequent IV Dosing & Tumor Microenvironment (TME) Study of Nemvaleukin Alfa (ALKS 4230) Monotherapy and in Combination With Pembrolizumab (ARTISTRY-3) (ARTISTRY-3)

• ClinicalTrials.gov Identifier: NCT04592653
• Recruitment Status: Recruiting
• First Posted: October 19, 2020
• Last Update Posted: January 24, 2024
• Sponsor: Mural Oncology, Inc
• Information provided by (Responsible Party): Mural Oncology, Inc

Tracking Information

• First Submitted Date: August 24, 2020
• First Posted Date: October 19, 2020
• Last Update Posted Date: January 24, 2024
• Actual Study Start Date: September 30, 2020
• Estimated Primary Completion Date: July 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 6, 2022)

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

Original 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 ]

Current Secondary Outcome Measures (submitted: May 6, 2022)

• 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 ]
• 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) ]
• Incidence of 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 (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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Less Frequent IV Dosing & Tumor Microenvironment (TME) Study of Nemvaleukin Alfa (ALKS 4230) Monotherapy and in Combination With Pembrolizumab (ARTISTRY-3)
• 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumor

Intervention

• Biological: Nemvaleukin alfa
  IV infusion over 30 minutes
  Other Name: ALKS 4230
• Biological: Pembrolizumab
  IV infusion over 30 minutes
  Other Name: Keytruda

Study Arms

• 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
  Interventions:

  • Biological: Nemvaleukin alfa
  • Biological: Pembrolizumab
• Experimental: Cohort 2 Part A: Less Frequent IV Dosing Nemvaleukin
  Intervention: Biological: Nemvaleukin alfa
• Experimental: Cohort 2 Part B: Less Frequent IV Dosing Nemvaleukin and Pembrolizumab
  Interventions:

  • Biological: Nemvaleukin alfa
  • Biological: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 6, 2022): 78
• Original Estimated Enrollment (submitted: October 12, 2020): 36
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: July 2024 (Final data collection date for primary outcome measure)

Eligibility 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
• For Cohort 1 (TME), patients who have received prior anti-PD-1 directed therapy must wait at least 4 weeks from last dose of such therapy before the Screening biopsy is collected
• 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

Sex/Gender

• Sexes Eligible for Study: All

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

Contacts

Contact: Director Global Clinical Services; 781-614-0100 (US Only); clinicaltrials@muraloncology.com

• Listed Location Countries: Spain, 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

• Current Responsible Party: Mural Oncology, Inc
• Original Responsible Party: Alkermes, Inc.
• Current Study Sponsor: Mural Oncology, Inc
• Original Study Sponsor: Alkermes, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Sonali Panchabhai; Mural Oncology

• PRS Account: Mural Oncology, Inc
• Verification Date: January 2024