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

NCT04830124 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: ALKS 4230-006
• Study Type: interventional
• Target: 173
• Locations: 8 countries
• Sites: 41

Brief Summary

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

Conditions

Cutaneous Melanoma; Mucosal Melanoma

Keywords

ALKS 4230; Melanoma; Immunotherapy; Nemvaleukin alfa; IL-2; Interlukin-2; Oncology; Cytokine; Nemvaleukin; Mural Oncology; Pembrolizumab

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (15)

• Centrally-assessed duration of response (DOR) (Cohort 1 and 2)

  Assessed up to 2 years from the first dose

• Investigator-assessed duration of response (DOR) (Cohort 3 and 4)

  Assessed up to 2 years from the first dose

• Centrally-assessed progression free survival (PFS) (Cohort 1 and 2)

  Assessed up to 2 years from the first dose

• Investigator-assessed progression free survival (PFS) (Cohort 3 and 4)

  Assessed up to 2 years from the first dose

• Centrally-assessed disease control rate (DCR) (Cohort 1 and 2)

  Assessed up to 2 years from the first dose

Study Arms (4)

Advanced Cutaneous Melanoma Subcutaneous Dosing (Cohort 1)

EXPERIMENTAL

Patients with unresectable and/or metastatic cutaneous melanoma

Drug: Nemvaleukin Alfa Subcutaneous

Advanced mucosal melanoma with IV Dosing (Cohort 2)

EXPERIMENTAL

Patients with unresectable and/or metastatic mucosal melanoma

Drug: Nemvaleukin Alfa Intravenous

Advanced Cutaneous Melanoma with Less Frequent IV Dosing (Cohort 3)

EXPERIMENTAL

Patients with unresectable and/or metastatic cutaneous melanoma

Drug: Nemvaleukin Alfa Intravenous Less Frequent Dosing

Advanced Cutaneous Melanoma with Less Frequent IV Nemvaleukin Dosing + Pembrolizumab (Cohort 4)

EXPERIMENTAL

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; Drug: Pembrolizumab

Interventions

Nemvaleukin Alfa Subcutaneous DRUG

Subcutaneous injection of nemvaleukin every 7 days

Also known as: ALKS 4230 Subcutaneous

Advanced Cutaneous Melanoma Subcutaneous Dosing (Cohort 1)

Nemvaleukin Alfa Intravenous DRUG

Intravenous (IV) infusion over 30 minutes given daily for 5 consecutive days

Also known as: ALKS 4230 Intravenous

Advanced mucosal melanoma with IV Dosing (Cohort 2)

Nemvaleukin Alfa Intravenous Less Frequent Dosing DRUG

Intravenous (IV) infusion over 30 minutes twice every 21 days (Day 1 and Day 8 dosing of a 21 day cycle)

Also known as: ALKS 4230 Intravenous

Advanced Cutaneous Melanoma with Less Frequent IV Dosing (Cohort 3); Advanced Cutaneous Melanoma with Less Frequent IV Nemvaleukin Dosing + Pembrolizumab (Cohort 4)

Pembrolizumab DRUG

Cohort 4 only: 200mg IV pembrolizumab on Day 1 of a 21-day cycle

Also known as: Keytruda

Advanced Cutaneous Melanoma with Less Frequent IV Nemvaleukin Dosing + Pembrolizumab (Cohort 4)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mural Oncology, Inc: lead

Study Sites (41)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Orlando Health, Inc

Orlando, Florida, 32806, United States

Location

Norton Cancer Center

Louisville, Kentucky, 40018, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

NYU Laura and Isaac Perimutter Cancer Center

New York, New York, 10016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

UT Southwestern Medical Center of Dallas

Dallas, Texas, 75390, United States

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

John Flynn Private Hospital

Tugun, Queensland, 4224, Australia

Location

The Queen Elizabeth Hospital

Woodville, 5011, Australia

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

Location

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, H2X 1R9, Canada

Location

McGill University Health Center (MUHC)

Montreal, Quebec, H4A 3J1, Canada

Location

Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari

Bari, 70124, Italy

Location

Fondazione IRCC Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Veneto Oncology Institute

Padua, 35128, Italy

Location

Ospedale S. Maria della Misericordia

Perugia, 06132, Italy

Location

IRCCS Istituti Fisioterapici Ospitalieri

Roma, 144, Italy

Location

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte

Siena, 53100, Italy

Location

Kyungpook National University Chilgok Hospital

Daegu, Daegu, 41404, South Korea

Location

The Catholic Univ. of Korea, Seoul St. Marys Hospital

Seoul, Seocho-gu, 06591, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, Seodaemun-Gu, 03722, South Korea

Location

Samsung Medical Center

Gangam-gu, Seoul, 06351, South Korea

Location

Seoul National University Hospital

Jongno-gu, Seoul, 03080, South Korea

Location

Asan Medical Center

Songpa-Gu, Seoul, 05505, South Korea

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

Hospital Universitario Quiron Pozuelo

Madrid, Madrid, 28223, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital General Universitario

Madrid, 28007, Spain

Location

Hospital Regional de Málaga

Málaga, 29010, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Taipei Veterans General Hospital, VGHTPE

Taipei, Taipei, 112, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

Location

Chang Gung Memorial Hospital LinKou

Taoyuan District, 333, Taiwan

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

The Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

The Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Melanoma; Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Mural Oncology Medical Monitor

  Mural Oncology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2021
• First Posted: April 2, 2021
• Study Start: September 27, 2021
• Primary Completion: May 8, 2025
• Study Completion: May 8, 2025
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); CA (3); US (10); IT (6); ES (6); GB (3); KR (7); TW (3)