A Study of the Effects of ALKS 4230 (Nemvaleukin Alfa) on Subjects With Solid Tumors

A Phase 1/2 Study of ALKS 4230 Administered Intravenously as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors - ARTISTRY-1

To better understand the safety and tolerability of ALKS 4230 in humans

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: ALKS 4230; Drug: ALKS 4230 + pembrolizumab

Detailed Description

To investigate the safety and tolerability of ALKS 4230, determine the recommended Phase 2 dose (RP2D) and assess anti-tumor activity in Monotherapy and ALKS 4230 in Combination with pembrolizumab.

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Mural Oncology Investgational Site
    • Waratah, New South Wales, Australia, 2298
      • Mural Oncology Investigational Site
• Belgium
  • MO
    • Brussels, MO, Belgium, 1200
      • Mural Oncology Investigational Site
  • West-Vlaanderen
    • Kortrijk, West-Vlaanderen, Belgium, 8500
      • Mural Oncology Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • Mural Oncology Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada
      • Mural Oncology Investigational Site
    • Toronto, Ontario, Canada
      • Alkermes Investigational Site
  • Quebec
    • Montréal, Quebec, Canada
      • Mural Oncology Investigational Site
    • Québec, Quebec, Canada, G1R 2J6
      • Mural Oncology Investigational Site
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35015
    • Mural Oncology Investigational Site
  • Seoul, Korea, Republic of, 02841
    • Mural Oncology Investigational Site
  • Seoul, Korea, Republic of, 03722
    • Mural Oncology Investigational Site
• Poland
  • Poznan
    • Skorzewo, Poznan, Poland, 60-185
      • Mural Oncology Investigational Site
• Spain
  • Barcelona, Spain, 8036
    • Mural Oncology Investigational Site
  • Madrid, Spain, 28040
    • Mural Oncology Investigational Site
  • Madrid, Spain, 28041
    • Mural Oncology Investigational Site
  • Madrid, Spain, 28050
    • Mural Oncology Investigational Site
  • Madrid, Spain, 28033
    • Mural Oncology Investigational Site
  • Valencia, Spain, 46010
    • Mural Oncology Investigational Site
• United States
  • Colorado
    • Denver, Colorado, United States, 80045
      • Mural Oncology Investigational Site
  • Florida
    • Port Saint Lucie, Florida, United States, 34952
      • Mural Oncology Investigational Site
    • Tampa, Florida, United States, 33610
      • Mural Oncology Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Mural Oncology Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Mural Oncology Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 47201
      • Mural Oncology Investigational Site
  • New York
    • Buffalo, New York, United States, 14203
      • Mural Oncology Investigational Site
    • New York, New York, United States, 10016
      • Mural Oncology Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Mural Oncology Investigational Site
  • Texas
    • Dallas, Texas, United States, 75230
      • Mural Oncology Investigational Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Mural Oncology Investigational Site
  • Washington
    • Spokane, Washington, United States, 99208
      • Mural Oncology Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• For Part A, the subject has histological or cytological evidence of a solid tumor; for Part B, the subject has a diagnosis of melanoma or renal cell carcinoma
• All subjects must have advanced solid tumors that have returned after treatment with established approved therapies or be intolerant of established therapies
• Subjects enrolled in Part B or Part C must have at least 1 lesion that may qualify as a target lesion
• Subject can move around on their own, has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and has an estimated life expectancy of at least 3 months
• Subject must have adequate hematologic reserve
• 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 investigational agents must wait at least 4 weeks
• 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. A female not of childbearing potential is one who has undergone bilateral oophorectomies or who is postmenopausal, defined as >45 years of age and without a menstrual period for 12 consecutive months
• Meets contraceptive requirements defined in the protocol
• Additional criteria may apply

Exclusion Criteria:

• Subject is currently pregnant or breastfeeding, or is planning to become pregnant during the study
• Subjects with an active infection or with a fever >/= 38.5 degrees 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 have a mean QT interval corrected by the Fridericia Correction formula value of >470 msec (in females) or >450 msec (in males)
• Subjects with known hypersensitivity to any components of ALKS 4230
• Subjects with known hypersensitivity to any components of pembrolizumab (for patients in combination arm only)
• Subjects who require pharmacologic doses of corticosteroids; replacement doses, topical, ophthalmologic, and inhalational steroids are permitted
• Subjects who developed autoimmune disorders while on prior immunotherapy, including pneumonitis, nephritis, and neuropathy
• Subjects with any other concurrent uncontrolled illness, including mental illness or substance abuse, which may interfere with the ability of the subject 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
• Subjects with dyspnea at rest of requiring oxygen therapy
• Subjects active autoimmune disease requiring systemic treatment within the past 30 days
• Subjects who received radiotherapy within the last 4 weeks before start of study treatment administration with the exception of limited field palliative radiotherapy
• Subjects who have received systemic immunomodulatory agents within 28 days prior to C1D1.
• Subjects who have received administration of a live, attenuated vaccine within 4 weeks of Cycle 1, Day1.
• Prior solid organ and/or non-autologous hematopoietic stem cell or bone marrow transplant recipients
• Subjects who have received prior IL-2 based or IL-15 based cytokine therapy
• Additional criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALKS 4230 + pembrolizumab	Drug: ALKS 4230 + pembrolizumab; IV infusion of ALKS 4230 over 30 minutes given daily for 5 consecutive days followed by an off-treatment period; pembrolizumab administered IV once with ALKS 4230 on the first day of each cycle
Experimental: ALKS 4230	Drug: ALKS 4230; Intravenous (IV) infusion over 30 minutes given daily for 5 consecutive days followed by an off-treatment period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of adverse events (AEs) and dose-limiting toxicities (DLT) in study Part A	Incidence of AEs that are both serious and drug-related	From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months
Incidence of drug-related AEs in study Part B	Incidence of AEs that are drug-related	From time of initiation of therapy until 30 days after last dose of study drug, assessed up to 24 months
Overall response rate (ORR) of ALKS 4230 monotherapy in patients with melanoma or renal cell carcinoma (Part B) and in combination with pembrolizumab in patients with advanced solid tumors (Part C)	Proportion of patients with the confirmed overall response of complete response or partial response	From time of initiation of therapy until 30 days after last dose of study drug assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate	Proportion of subjects with objective evidence of CR, PR, or Stable Disease (SD)	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 CR/iCR or PR/iPR	Time from the first documentation of response (CR/iCR or PR/iPR) to the first documentation of objective tumor progression or death due to any cause	From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months
Serum concentrations of ALKS 4230 will be determined at various time points	Concentration vs time and standard pharmacokinetic (PK) parameters will be summarized by dose level	From time of initiation of therapy until the last treatment cycle, assessed up to 24 months
Serum will be assayed for the presence of anti-ALKS 4230 antibodies	Results will be summarized by dose level	From time of initiation of therapy until the last treatment cycle, assessed up to 24 months
Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry at various time points	Results will be summarized by dose level	From time of initiation of therapy until the last treatment cycle, assessed up to 24 months
Serum concentrations of proinflammatory cytokines will be assessed using a multiplex method at various time points	Results will be summarized by dose level	From time of initiation of therapy during the first two treatment cycles, assessed up to 2 months

Collaborators and Investigators

• Sponsor: Mural Oncology, Inc
• Investigators: Study Director: Medical Director, Mural Oncology

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): August 2, 2023
• Study Completion (Actual): August 2, 2023

Study Registration Dates

• First Submitted: June 1, 2016
• First Submitted That Met QC Criteria: June 9, 2016
• First Posted (Estimated): June 14, 2016

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Solid tumors; Immunotherapy; Melanoma; IL-2; Renal cell carcinoma; Interleukin-2; Non-small-cell lung cancer; Squamous cell carcinoma of the head and neck; in combination with pembrolizumab
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: ALK4230-A101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: At this time, IPD sharing has not been defined and/or decided if it will be shared.