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

NCT ID: NCT04830124

Last Updated: 2025-06-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

173 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-27

Study Completion Date

2025-05-08

Brief Summary

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

Detailed Description

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Conditions

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Cutaneous Melanoma Mucosal Melanoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Advanced Cutaneous Melanoma Subcutaneous Dosing (Cohort 1)

Patients with unresectable and/or metastatic cutaneous melanoma

Group Type EXPERIMENTAL

Nemvaleukin Alfa Subcutaneous

Intervention Type DRUG

Subcutaneous injection of nemvaleukin every 7 days

Advanced mucosal melanoma with IV Dosing (Cohort 2)

Patients with unresectable and/or metastatic mucosal melanoma

Group Type EXPERIMENTAL

Nemvaleukin Alfa Intravenous

Intervention Type DRUG

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

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

Patients with unresectable and/or metastatic cutaneous melanoma

Group Type EXPERIMENTAL

Nemvaleukin Alfa Intravenous Less Frequent Dosing

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Nemvaleukin Alfa Intravenous Less Frequent Dosing

Intervention Type DRUG

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

Pembrolizumab

Intervention Type DRUG

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

Interventions

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Nemvaleukin Alfa Subcutaneous

Subcutaneous injection of nemvaleukin every 7 days

Intervention Type DRUG

Nemvaleukin Alfa Intravenous

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

Intervention Type 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)

Intervention Type DRUG

Pembrolizumab

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

Intervention Type DRUG

Other Intervention Names

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ALKS 4230 Subcutaneous ALKS 4230 Intravenous ALKS 4230 Intravenous Keytruda

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mural Oncology, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mural Oncology Medical Monitor

Role: STUDY_DIRECTOR

Mural Oncology

Locations

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UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status

The Angeles Clinic and Research Institute

Los Angeles, California, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

Orlando Health, Inc

Orlando, Florida, United States

Site Status

Norton Cancer Center

Louisville, Kentucky, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

NYU Laura and Isaac Perimutter Cancer Center

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

UT Southwestern Medical Center of Dallas

Dallas, Texas, United States

Site Status

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Site Status

John Flynn Private Hospital

Tugun, Queensland, Australia

Site Status

The Queen Elizabeth Hospital

Woodville, , Australia

Site Status

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, Canada

Site Status

McGill University Health Center (MUHC)

Montreal, Quebec, Canada

Site Status

Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari

Bari, , Italy

Site Status

Fondazione IRCC Istituto Nazionale dei Tumori

Milan, , Italy

Site Status

Veneto Oncology Institute

Padua, , Italy

Site Status

Ospedale S. Maria della Misericordia

Perugia, , Italy

Site Status

IRCCS Istituti Fisioterapici Ospitalieri

Roma, , Italy

Site Status

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte

Siena, , Italy

Site Status

Kyungpook National University Chilgok Hospital

Daegu, Daegu, South Korea

Site Status

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

Seoul, Seocho-gu, South Korea

Site Status

Severance Hospital Yonsei University Health System

Seoul, Seodaemun-Gu, South Korea

Site Status

Samsung Medical Center

Gangam-gu, Seoul, South Korea

Site Status

Seoul National University Hospital

Jongno-gu, Seoul, South Korea

Site Status

Asan Medical Center

Songpa-Gu, Seoul, South Korea

Site Status

Chungnam National University Hospital

Daejeon, , South Korea

Site Status

Hospital Universitario Quiron Pozuelo

Madrid, Madrid, Spain

Site Status

Hospital Clinic Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital General Universitario

Madrid, , Spain

Site Status

Hospital Regional de Málaga

Málaga, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Taipei Veterans General Hospital, VGHTPE

Taipei, Taipei, Taiwan

Site Status

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Chang Gung Memorial Hospital LinKou

Taoyuan District, , Taiwan

Site Status

Royal Marsden Hospital

London, , United Kingdom

Site Status

The Christie Hospital

Manchester, , United Kingdom

Site Status

The Churchill Hospital

Oxford, , United Kingdom

Site Status

Countries

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United States Australia Canada Italy South Korea Spain Taiwan United Kingdom

Other Identifiers

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ALKS 4230-006

Identifier Type: -

Identifier Source: org_study_id

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