Nemvaleukin Alfa Monotherapy and in Combination With Pembrolizumab in Patients With Advanced Cutaneous or Mucosal Melanoma - ARTISTRY-6 (ARTISTRY-6)

A Phase 2, Open-Label, Multicenter, Cohort Study of Nemvaleukin Alfa (ALKS 4230) Monotherapy and in Combination With Pembrolizumab in Patients With Advanced Cutaneous Melanoma or Advanced Mucosal Melanoma - ARTISTRY-6

This study observes the antitumor activity, safety, tolerability, PK, and pharmacodynamics in patients with inoperable and/or metastatic melanoma

Study Overview

• Status: Terminated
• Conditions: Cutaneous Melanoma; Mucosal Melanoma
• Intervention / Treatment: Drug: Nemvaleukin Alfa Subcutaneous; Drug: Nemvaleukin Alfa Intravenous; Drug: Nemvaleukin Alfa Intravenous Less Frequent Dosing; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Woodville, Australia, 5011
    • The Queen Elizabeth Hospital
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Queensland
    • Tugun, Queensland, Australia, 4224
      • John Flynn Private Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X 1R9
      • Centre hospitalier de l'Université de Montréal (CHUM)
    • Montréal, Quebec, Canada, H4A 3J1
      • McGill University Health Center (MUHC)
• Italy
  • Bari, Italy, 70124
    • Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari
  • Milano, Italy, 20133
    • Fondazione IRCC Istituto Nazionale dei Tumori
  • Padova, Italy, 35128
    • Veneto Oncology Institute
  • Perugia, Italy, 06132
    • Ospedale S. Maria Della Misericordia
  • Roma, Italy, 144
    • IRCCS Istituti Fisioterapici Ospitalieri
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
• Korea, Republic of
  • Daegu, Korea, Republic of, 41404
    • Kyungpook National University Chilgok Hospital
  • Daejeon, Korea, Republic of, 35015
    • Chungnam National University Hospital
  • Seocho-gu
    • Seoul, Seocho-gu, Korea, Republic of, 06591
      • The Catholic Univ. of Korea, Seoul St. Marys Hospital
  • Seodaemun-Gu
    • Seoul, Seodaemun-Gu, Korea, Republic of, 03722
      • Severance Hospital Yonsei University Health System
  • Seoul
    • Gangam-gu, Seoul, Korea, Republic of, 06351
      • Samsung Medical Center
    • Jongno-gu, Seoul, Korea, Republic of, 03080
      • Seoul National University Hospital
    • Songpa-Gu, Seoul, Korea, Republic of, 05505
      • Asan Medical Center
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic Barcelona
  • Barcelona, Spain, 8035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28007
    • Hospital General Universitario
  • Madrid, Spain, 28223
    • Hospital Universitario Quiron Pozuelo
  • Málaga, Spain, 29010
    • Hospital Regional de Malaga
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Kaohsiung Chang Gung Memorial Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital, VGHTPE
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital Linkou
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
  • Oxford, United Kingdom, OX3 7LE
    • The Churchill Hospital
• United States
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Orlando, Florida, United States, 32806
      • Orlando Health, Inc
  • Kentucky
    • Louisville, Kentucky, United States, 40018
      • Norton Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • NYU Laura and Isaac Perimutter Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center of Dallas

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The patient must have the following tumor types:

Cohort 1: Patient has unresectable and/or metastatic cutaneous melanoma. No more than 5 patients with acral melanoma may enroll in this cohort.

Cohort 2: Patient has unresectable and/or metastatic mucosal melanoma.

Cohort 3: Patient has unresectable and/or metastatic cutaneous melanoma. Patients with acral melanoma may not enroll in this cohort.

Cohort 4: Patient has unresectable and/or metastatic cutaneous melanoma. No patients with mucosal or acral melanoma may enroll in this cohort.

- The patient must have received previous treatment as follows: Cohorts 1 and 2: Patient has received anti-PD-[L]1 therapy with or without anti-CTLA-4 therapy, and less than or equal to one other prior regimen of systemic anti-neoplastic therapy (eg, targeted therapy, chemotherapy). Previous adjuvant and/or neoadjuvant therapy counts as one prior regimen. Patients have experienced objective response (partial response [PR] or CR; by RECIST 1.1 or iRECIST) or stable disease (SD; by RECIST 1.1 or iRECIST) as best overall response (BOR) to anti-PD-[L]1 therapy. Patients with confirmed progressive disease (by RECIST 1.1 or iRECIST) as best response may be included, if they received anti-PD-[L]1 therapy for a minimum of 12 weeks (eg, from first dose to last dose). Patients with BRAF mutations may or may not have received prior targeted therapy.

Cohort 3: Patients who have received anti-PD-[L]1 therapy with or without anti-CTLA-4 therapy or anti-lymphocyte-activation gene 3 (LAG-3) therapy, and ≤1 other prior regimen of systemic anti-neoplastic therapy (eg, targeted therapy, chemotherapy). Previous adjuvant and/or neoadjuvant therapy counts as 1 prior regimen. Patients must have experienced objective response (PR or CR by RECIST 1.1 or iRECIST) or stable disease (by RECIST 1.1 or iRECIST) as BOR to anti PD-[L]1 therapy. Patients with confirmed progressive disease (by RECIST 1.1 or iRECIST) as best response may be included, if they received anti-PD-[L]1 therapy for ≥12 weeks (from first dose to last dose). Patients with BRAF mutations may or may not have received prior targeted therapy.

Cohort 4: Patients must not have received prior systemic anticancer therapy for unresectable or metastatic melanoma. Prior adjuvant and/or neoadjuvant PD-[L]1 treatments are allowed if there is at least 6 months between the last dose and date of recurrence.

Cohorts 1, 2, and 3 - Patients who have received prior treatment with talimogene laherparepvec (TVEC) are allowed to enroll provided that last exposure to TVEC was ≥28 days prior to first exposure to nemvaleukin and that all injection-site reactions to TVEC have resolved. TVEC shall not be considered a prior regimen of systemic anti-neoplastic therapy, nor shall it be considered a systemic immunomodulatory agent.

• Patients must have disease that is measurable based on RECIST 1.1., that has not recently been irradiated or used to collect a biopsy.
• Cohorts 1 and 2 (required), Cohort 3 (optional), Cohort 4 (may be required, otherwise optional). Patient is willing to undergo a pretreatment tumor biopsy or provide qualifying archival tumor tissue.

Cohort 4 - Patients are required to have known tumor PD-[L]1 status determined by local testing using an approved assay. PD-[L]1 testing performed prior to enrolling on the study is acceptable if there was no intervening systemic anti-cancer therapy, and archival tissue may be used for testing provided the biopsy is ≤3 months old.

• Patient has an Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 and an estimated life expectancy of ≥3 months.
• Additional criteria may apply.

Exclusion Criteria:

• Patient has uveal melanoma (all cohorts) or acral melanoma (Cohort 2, Cohort 3 and Cohort 4).
• Patient has received prior interleukin (IL)-2-based or IL-15-based cytokine therapy; patient has had exposure, including intralesional, to IL-12 or analogs thereof.
• Patient requires systemic corticosteroids (>10 mg of prednisone daily, or equivalent) however, replacement doses, topical, ophthalmologic, and inhalational steroids are permitted.
• Patient has undergone prior solid organ and/or non-autologous hematopoietic stem cell or bone marrow transplant.
• Patient is currently pregnant, breastfeeding, or is planning to become pregnant or to begin breastfeeding during the study period or within 30 days (Cohorts 1,2, and 3) or 120 days (Cohort 4) after last study drug administration.
• Patients with active or symptomatic central nervous system metastases unless the metastases have been treated by surgery and/or radiation therapy and/or gamma knife, the subject has been tapered to a dose of 10 mg of prednisone (or equivalent) or less of corticosteroids for at least 2 weeks before the first dose, and the subject is neurologically stable. Patients with leptomeningeal disease are excluded.
• Patient has known or suspected hypersensitivity to any components of nemvaleukin (all cohorts) or to pembrolizumab (cohort 4 only).
• Patients with an uncontrollable bleeding disorder.
• Patient has QT interval corrected by the Fridericia Correction Formula values of >470 msec (in females) or >450 msec (in males); patient who is known to have congenital prolonged QT syndromes; or patient who is on medications known to cause prolonged QT interval on ECG.
• Patient has developed Grade ≥3 immune-related AEs (irAEs) while on prior immunotherapy, (eg, pneumonitis and nephritis) and has not recovered to ≤Grade 1 and/or are on systemic steroids within 14 days of first dose of study drug.
• Patients who have previously discontinued immunotherapy due to immune-related adverse event (irAEs) will be excluded.
• Cohort 4 only: Patient has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
• 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Advanced Cutaneous Melanoma Subcutaneous Dosing (Cohort 1); Patients with unresectable and/or metastatic cutaneous melanoma	Drug: Nemvaleukin Alfa Subcutaneous; Subcutaneous injection of nemvaleukin every 7 days; Other Names: ALKS 4230 Subcutaneous
Experimental: Advanced mucosal melanoma with IV Dosing (Cohort 2); Patients with unresectable and/or metastatic mucosal melanoma	Drug: Nemvaleukin Alfa Intravenous; Intravenous (IV) infusion over 30 minutes given daily for 5 consecutive days; Other Names: ALKS 4230 Intravenous
Experimental: Advanced Cutaneous Melanoma with Less Frequent IV Dosing (Cohort 3); Patients with unresectable and/or metastatic cutaneous melanoma	Drug: Nemvaleukin Alfa Intravenous Less Frequent Dosing; Intravenous (IV) infusion over 30 minutes twice every 21 days (Day 1 and Day 8 dosing of a 21 day cycle); Other Names: ALKS 4230 Intravenous
Experimental: Advanced Cutaneous Melanoma with Less Frequent IV Nemvaleukin Dosing + Pembrolizumab (Cohort 4); Patients with unresectable and/or metastatic cutaneous melanoma. Patients must not have received prior systemic anticancer therapy for unresectable or metastatic melanoma. Prior adjuvant and/or neoadjuvant PD-[L]1 treatments are allowed if there is at least 6 months between the last dose and date of recurrence.	Drug: Nemvaleukin Alfa Intravenous Less Frequent Dosing; Intravenous (IV) infusion over 30 minutes twice every 21 days (Day 1 and Day 8 dosing of a 21 day cycle); Other Names: ALKS 4230 Intravenous; Drug: Pembrolizumab; Cohort 4 only: 200mg IV pembrolizumab on Day 1 of a 21-day cycle; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Centrally-assessed overall response rate (ORR) (Cohort 1 and 2)	ORR is defined as the number of patients exhibiting a complete response (CR) or partial response (PR) divided by the number of patients who received the study drug; Response will be based on RECIST v1.1 criteria	Assessed up to 2 years from the first dose
Investigator-assessed overall response rate (ORR) (Cohort 3 and 4)	ORR is defined as the number of patients exhibiting a complete response (CR) or partial response (PR) divided by the number of patients who received the study drug	Assessed up to 2 years from the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Centrally-assessed duration of response (DOR) (Cohort 1 and 2)	-DOR is defined as the time from the first documentation of complete or partial response to the first documentation of either objective tumor progression or death	Assessed up to 2 years from the first dose
Centrally-assessed progression free survival (PFS) (Cohort 1 and 2)	-PFS is defined as the time from each respective patient's first dose of nemvaleukin to either the first documentation of objective tumor progression or death	Assessed up to 2 years from the first dose
Centrally-assessed disease control rate (DCR) (Cohort 1 and 2)	-DCR is defined as the proportion of patients with objective evidence of complete response, partial response, or stable disease on 2 consecutive protocol-required disease assessments	Assessed up to 2 years from the first dose
Centrally-assessed time to response (TTR) (Cohort 1 and 2)	-TTR is defined as the time from patient's first dose of nemvaleukin to the first documentation of complete response or partial response	Assessed up to 2 years from the first dose
Incidence of treatment-emergent adverse events (All cohorts)		Assessed up to 2 years from the first dose
Investigator-assessed overall response rate (ORR) (Cohort 1 and 2)	ORR is defined as the number of patients exhibiting a complete response (CR) or partial response (PR) divided by the number of patients who received the study drug	Assessed up to 2 years from the first dose
Investigator-assessed immune overall response rate (iORR) (All cohorts)	-iORR is defined as the number of patients exhibiting a complete response (CR) or partial response (PR) divided by the number of patients who received the study drug.	Assessed up to 2 years from the first dose
Investigator-assessed immune duration of response (iDOR) (All cohorts)	-iDOR is defined as the time from the first documentation of complete or partial response to the first documentation of either objective tumor progression or death	Assessed up to 2 years from the first dose
Investigator-assessed immune progression free survival (iPFS) (All cohorts)	-iPFS is defined as the time from each respective patient's first dose of nemvaleukin to either the first documentation of objective tumor progression or death	Assessed up to 2 years from the first dose
Investigator-assessed immune disease control rate (iDCR) (All cohorts)	-iDCR is defined as the proportion of patients with objective evidence of complete response, partial response, or stable disease on 2 consecutive protocol-required disease assessments	Assessed up to 2 years from the first dose
Investigator-assessed immune time to response (iTTR) (All cohorts)	-iTTR is defined as the time from patient's first dose of nemvaleukin to the first documentation of complete or partial response	Assessed up to 2 years from the first dose
Investigator-assessed duration of response (DOR) (Cohort 3 and 4)	-DOR is defined as the time from the first documentation of complete or partial response to the first documentation of either objective tumor progression or death	Assessed up to 2 years from the first dose
Investigator-assessed progression free survival (PFS) (Cohort 3 and 4)	-PFS is defined as the time from each respective patient's first dose of nemvaleukin to either the first documentation of objective tumor progression or death	Assessed up to 2 years from the first dose
Investigator-assessed disease control rate (DCR) (Cohort 3 and 4)	-DCR is defined as the proportion of patients with objective evidence of complete response, partial response, or stable disease on 2 consecutive protocol-required disease assessments	Assessed up to 2 years from the first dose
Investigator-assessed time to response (TTR) (Cohort 3 and 4)	-TTR is defined as the time from patient's first dose of nemvaleukin to the first documentation of complete response or partial response	Assessed up to 2 years from the first dose

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2021
• Primary Completion (Actual): May 8, 2025
• Study Completion (Actual): May 8, 2025

Study Registration Dates

• First Submitted: April 1, 2021
• First Submitted That Met QC Criteria: April 1, 2021
• First Posted (Actual): April 2, 2021

Study Record Updates

• Last Update Posted (Actual): June 10, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; Pembrolizumab; Melanoma; Oncology; Cytokine; ALKS 4230; Nemvaleukin alfa; IL-2; Interlukin-2; Nemvaleukin; Mural Oncology
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma, Cutaneous Malignant; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: ALKS 4230-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No