Clinical trial NCT04830124: Nemvaleukin Alfa Monotherapy and in Combination With Pembrolizumab in Patients With Advanced Cutaneous or Mucosal Melanoma - ARTISTRY-6
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cutaneous Melanoma
Mucosal Melanoma
Keywords: ALKS 4230
Melanoma
Immunotherapy
Nemvaleukin alfa
IL-2
Interlukin-2
Oncology
Cytokine
Nemvaleukin
Mural Oncology
Pembrolizumab
Lead sponsor: Mural Oncology, Inc
Sponsor class: INDUSTRY
First posted: 2021-04-02
Enrollment: 173
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Centrally-assessed overall response rate (ORR) (Cohort 1 and 2)
timeFrame: Assessed up to 2 years from the first dose
measure: Investigator-assessed overall response rate (ORR) (Cohort 3 and 4)
timeFrame: Assessed up to 2 years from the first dose
Secondary outcomes:
measure: Centrally-assessed duration of response (DOR) (Cohort 1 and 2)
timeFrame: Assessed up to 2 years from the first dose
measure: Investigator-assessed duration of response (DOR) (Cohort 3 and 4)
timeFrame: Assessed up to 2 years from the first dose
measure: Centrally-assessed progression free survival (PFS) (Cohort 1 and 2)
timeFrame: Assessed up to 2 years from the first dose
measure: Investigator-assessed progression free survival (PFS) (Cohort 3 and 4)
timeFrame: Assessed up to 2 years from the first dose
measure: Centrally-assessed disease control rate (DCR) (Cohort 1 and 2)
timeFrame: Assessed up to 2 years from the first dose
measure: Investigator-assessed disease control rate (DCR) (Cohort 3 and 4)
timeFrame: Assessed up to 2 years from the first dose
measure: Centrally-assessed time to response (TTR) (Cohort 1 and 2)
timeFrame: Assessed up to 2 years from the first dose
measure: Investigator-assessed time to response (TTR) (Cohort 3 and 4)
timeFrame: Assessed up to 2 years from the first dose
measure: Incidence of treatment-emergent adverse events (All cohorts)
timeFrame: Assessed up to 2 years from the first dose
measure: Investigator-assessed overall response rate (ORR) (Cohort 1 and 2)
timeFrame: Assessed up to 2 years from the first dose
measure: Investigator-assessed immune overall response rate (iORR) (All cohorts)
timeFrame: Assessed up to 2 years from the first dose
measure: Investigator-assessed immune duration of response (iDOR) (All cohorts)
timeFrame: Assessed up to 2 years from the first dose
measure: Investigator-assessed immune progression free survival (iPFS) (All cohorts)
timeFrame: Assessed up to 2 years from the first dose
measure: Investigator-assessed immune disease control rate (iDCR) (All cohorts)
timeFrame: Assessed up to 2 years from the first dose
measure: Investigator-assessed immune time to response (iTTR) (All cohorts)
timeFrame: Assessed up to 2 years from the first dose
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc
state: Florida
city: Louisville
country: United States
facility: Norton Cancer Center
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: NYU Laura and Isaac Perimutter Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Dallas
country: United States
facility: UT Southwestern Medical Center of Dallas
state: Texas
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Tugun
country: Australia
facility: John Flynn Private Hospital
state: Queensland
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Center (MUHC)
state: Quebec
city: Bari
country: Italy
facility: Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
city: Milano
country: Italy
facility: Fondazione IRCC Istituto Nazionale dei Tumori
city: Padova
country: Italy
facility: Veneto Oncology Institute
city: Perugia
country: Italy
facility: Ospedale S. Maria della Misericordia
city: Roma
country: Italy
facility: IRCCS Istituti Fisioterapici Ospitalieri
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
city: Seoul
country: Korea, Republic of
facility: The Catholic Univ. of Korea, Seoul St. Marys Hospital
state: Seocho-gu
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seodaemun-Gu
city: Gangam-gu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul
city: Jongno-gu
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul
city: Songpa-Gu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario
city: Madrid
country: Spain
facility: Hospital Universitario Quiron Pozuelo
city: Málaga
country: Spain
facility: Hospital Regional de Málaga
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital, VGHTPE
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital LinKou
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Oxford
country: United Kingdom
facility: The Churchill Hospital
Study officials:
affiliation: Mural Oncology
name: Mural Oncology Medical Monitor
role: STUDY_DIRECTOR
References: