Nemvaleukin Alfa (ALKS 4230) Monotherapy in Patients With Advanced Cutaneous Melanoma or Advanced Mucosal Melanoma - ARTISTRY-6

Study Overview
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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 following prior anti-PD-[L]-1 therapy

Official Title
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A Phase 2, Open Label, Multicenter, Cohort Study of Nemvaleukin Alfa (ALKS 4230) Monotherapy in Patients With Advanced Cutaneous Melanoma or Advanced Mucosal Melanoma Who Have Previously Received Anti-PD-[L]-1 Therapy - ARTISTRY-6

Conditions
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Cutaneous Melanoma, Mucosal Melanoma

Intervention / Treatment
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* Drug: Nemvaleukin Alfa Subcutaneous
* Drug: Nemvaleukin Alfa Intravenous
* Drug: Nemvaleukin Alfa Intravenous Less Frequent Dosing


Participation Criteria
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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. The patient must have received previous treatment as follows: Patient has received anti-PD-[L]1 therapy with or without anti-CTLA-4 therapy, and no more than 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. Patients must have disease that is measurable based on RECIST 1.1., that has not recently been irradiated or used to collect a biopsy. Patient is willing to undergo a pretreatment tumor biopsy or provide qualifying archival tumor tissue. 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 and Cohort 3). 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 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. 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. Additional criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Advanced Cutaneous Melanoma Subcutaneous Dosing (Cohort 1)<br>Patients with unresectable and/or metastatic cutaneous melanoma | Drug: Nemvaleukin Alfa Subcutaneous<br>* Subcutaneous injection of nemvaleukin every 7 days<br>* Other names: ALKS 4230 Subcutaneous;|
| Experimental: Advanced mucosal melanoma with IV Dosing (Cohort 2)<br>Patients with unresectable and/or metastatic mucosal melanoma | Drug: Nemvaleukin Alfa Intravenous<br>* Intravenous (IV) infusion over 30 minutes given daily for 5 consecutive days<br>* Other names: ALKS 4230 Intravenous;|
| Experimental: Advanced Cutaneous Melanoma with Less Frequent IV Dosing (Cohort 3)<br>Patients with unresectable and/or metastatic cutaneous melanoma | Drug: Nemvaleukin Alfa Intravenous Less Frequent Dosing<br>* Intravenous (IV) infusion over 30 minutes once every 21 days or twice every 21 days<br>* Other names: ALKS 4230 Intravenous;|

What is the study measuring?
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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) | 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 duration of response (DOR) (All cohorts) | -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) (All cohorts) | -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 | Up to 2 years from the first dose | 
| Investigator-assessed disease control rate (DCR) (All cohorts) | -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) (All cohorts) | -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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alkermes, ALKS 4230, Melanoma, Immunotherapy, Nemvaleukin alfa, IL-2, Interlukin-2, Oncology, Cytokine, Nemvaleukin