NCT04830124

Terminated

Phase 2

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

Mural Oncology, Inc41 sites in 8 countries173 target enrollmentSeptember 27, 2021

ConditionsCutaneous Melanoma Mucosal Melanoma

InterventionsNemvaleukin Alfa Subcutaneous Nemvaleukin Alfa Intravenous Nemvaleukin Alfa Intravenous Less Frequent Dosing Pembrolizumab

DrugsNemvaleukin Alfa Subcutaneous Nemvaleukin Alfa Intravenous Nemvaleukin Alfa Intravenous Less Frequent Dosing Pembrolizumab

Overview

Phase: Phase 2
Intervention: Nemvaleukin Alfa Subcutaneous
Conditions: Cutaneous Melanoma
Sponsor: Mural Oncology, Inc
Enrollment: 173
Locations: 41
Primary Endpoint: Centrally-assessed overall response rate (ORR) (Cohort 1 and 2)
Status: Terminated
Last Updated: 10 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

Registry

clinicaltrials.gov

Start Date

September 27, 2021

End Date

May 8, 2025

Last Updated

10 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Mural Oncology, Inc

Responsible Party

Sponsor

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.

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.

Arms & Interventions

Advanced Cutaneous Melanoma Subcutaneous Dosing (Cohort 1)

Patients with unresectable and/or metastatic cutaneous melanoma

Intervention: Nemvaleukin Alfa Subcutaneous

Advanced mucosal melanoma with IV Dosing (Cohort 2)

Patients with unresectable and/or metastatic mucosal melanoma

Intervention: Nemvaleukin Alfa Intravenous

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

Patients with unresectable and/or metastatic cutaneous melanoma

Intervention: Nemvaleukin Alfa Intravenous Less Frequent Dosing

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.

Intervention: Nemvaleukin Alfa Intravenous Less Frequent Dosing

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

Intervention: Pembrolizumab

Outcomes

Primary Outcomes

Centrally-assessed overall response rate (ORR) (Cohort 1 and 2)

Time Frame: Assessed up to 2 years from the first dose

* 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

Investigator-assessed overall response rate (ORR) (Cohort 3 and 4)

Time Frame: Assessed up to 2 years from the first dose

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

Secondary Outcomes

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)
Investigator-assessed disease control rate (DCR) (Cohort 3 and 4)(Assessed up to 2 years from the first dose)
Centrally-assessed time to response (TTR) (Cohort 1 and 2)(Assessed up to 2 years from the first dose)
Investigator-assessed time to response (TTR) (Cohort 3 and 4)(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)(Assessed up to 2 years from the first dose)
Investigator-assessed immune overall response rate (iORR) (All cohorts)(Assessed up to 2 years from the first dose)
Investigator-assessed immune duration of response (iDOR) (All cohorts)(Assessed up to 2 years from the first dose)
Investigator-assessed immune progression free survival (iPFS) (All cohorts)(Assessed up to 2 years from the first dose)
Investigator-assessed immune disease control rate (iDCR) (All cohorts)(Assessed up to 2 years from the first dose)
Investigator-assessed immune time to response (iTTR) (All cohorts)(Assessed up to 2 years from the first dose)