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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04830124




Registration number
NCT04830124
Ethics application status
Date submitted
1/04/2021
Date registered
2/04/2021

Titles & IDs
Public title
Nemvaleukin Alfa Monotherapy and in Combination With Pembrolizumab in Patients With Advanced Cutaneous or Mucosal Melanoma - ARTISTRY-6
Scientific 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
Secondary ID [1] 0 0
ALKS 4230-006
Universal Trial Number (UTN)
Trial acronym
ARTISTRY-6
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cutaneous Melanoma 0 0
Mucosal Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nemvaleukin Alfa Subcutaneous
Treatment: Drugs - Nemvaleukin Alfa Intravenous
Treatment: Drugs - Nemvaleukin Alfa Intravenous Less Frequent Dosing
Treatment: Drugs - Pembrolizumab

Experimental: Advanced Cutaneous Melanoma Subcutaneous Dosing (Cohort 1) - Patients with unresectable and/or metastatic cutaneous melanoma

Experimental: Advanced mucosal melanoma with IV Dosing (Cohort 2) - Patients with unresectable and/or metastatic mucosal melanoma

Experimental: Advanced Cutaneous Melanoma with Less Frequent IV Dosing (Cohort 3) - Patients with unresectable and/or metastatic cutaneous melanoma

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.


Treatment: Drugs: Nemvaleukin Alfa Subcutaneous
Subcutaneous injection of nemvaleukin every 7 days

Treatment: Drugs: Nemvaleukin Alfa Intravenous
Intravenous (IV) infusion over 30 minutes given daily for 5 consecutive days

Treatment: Drugs: 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)

Treatment: Drugs: Pembrolizumab
Cohort 4 only: 200mg IV pembrolizumab on Day 1 of a 21-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Centrally-assessed overall response rate (ORR) (Cohort 1 and 2)
Timepoint [1] 0 0
Assessed up to 2 years from the first dose
Primary outcome [2] 0 0
Investigator-assessed overall response rate (ORR) (Cohort 3 and 4)
Timepoint [2] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [1] 0 0
Centrally-assessed duration of response (DOR) (Cohort 1 and 2)
Timepoint [1] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [2] 0 0
Investigator-assessed duration of response (DOR) (Cohort 3 and 4)
Timepoint [2] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [3] 0 0
Centrally-assessed progression free survival (PFS) (Cohort 1 and 2)
Timepoint [3] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [4] 0 0
Investigator-assessed progression free survival (PFS) (Cohort 3 and 4)
Timepoint [4] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [5] 0 0
Centrally-assessed disease control rate (DCR) (Cohort 1 and 2)
Timepoint [5] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [6] 0 0
Investigator-assessed disease control rate (DCR) (Cohort 3 and 4)
Timepoint [6] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [7] 0 0
Centrally-assessed time to response (TTR) (Cohort 1 and 2)
Timepoint [7] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [8] 0 0
Investigator-assessed time to response (TTR) (Cohort 3 and 4)
Timepoint [8] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [9] 0 0
Incidence of treatment-emergent adverse events (All cohorts)
Timepoint [9] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [10] 0 0
Investigator-assessed overall response rate (ORR) (Cohort 1 and 2)
Timepoint [10] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [11] 0 0
Investigator-assessed immune overall response rate (iORR) (All cohorts)
Timepoint [11] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [12] 0 0
Investigator-assessed immune duration of response (iDOR) (All cohorts)
Timepoint [12] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [13] 0 0
Investigator-assessed immune progression free survival (iPFS) (All cohorts)
Timepoint [13] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [14] 0 0
Investigator-assessed immune disease control rate (iDCR) (All cohorts)
Timepoint [14] 0 0
Assessed up to 2 years from the first dose
Secondary outcome [15] 0 0
Investigator-assessed immune time to response (iTTR) (All cohorts)
Timepoint [15] 0 0
Assessed up to 2 years from the first dose

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2026
Actual
Sample size
Target
180
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 0 0
John Flynn Private Hospital - Tugun
Recruitment hospital [3] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
4224 - Tugun
Recruitment postcode(s) [3] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
Italy
State/province [10] 0 0
Bari
Country [11] 0 0
Italy
State/province [11] 0 0
Milano
Country [12] 0 0
Italy
State/province [12] 0 0
Padova
Country [13] 0 0
Italy
State/province [13] 0 0
Perugia
Country [14] 0 0
Italy
State/province [14] 0 0
Roma
Country [15] 0 0
Italy
State/province [15] 0 0
Siena
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Seocho-gu
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Seodaemun-Gu
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Daegu
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Daejeon
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Spain
State/province [23] 0 0
Málaga
Country [24] 0 0
Spain
State/province [24] 0 0
Zaragoza
Country [25] 0 0
Taiwan
State/province [25] 0 0
Kaohsiung
Country [26] 0 0
Taiwan
State/province [26] 0 0
Taipei
Country [27] 0 0
Taiwan
State/province [27] 0 0
Taoyuan
Country [28] 0 0
United Kingdom
State/province [28] 0 0
London
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Manchester
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Mural Oncology, Inc
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mural Oncology Medical Monitor
Address 0 0
Mural Oncology
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Mural Oncology Clinical Trials
Address 0 0
Country 0 0
Phone 0 0
781-614-0100 (US Only)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04830124