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

• ClinicalTrials.gov Identifier: NCT04830124
• Recruitment Status: Recruiting
• First Posted: April 2, 2021
• Last Update Posted: January 11, 2022
• Sponsor: Alkermes, Inc.
• Information provided by (Responsible Party): Alkermes, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Cutaneous Melanoma; Mucosal Melanoma	Drug: Nemvaleukin Alfa Subcutaneous; Drug: Nemvaleukin Alfa Intravenous	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 110 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-label, Multicenter, Cohort Study of Nemvaleukin Alfa (ALKS 4230) Monotherapy Administered Subcutaneously in Patients With Advanced Cutaneous Melanoma or Intravenously in Patients With Advanced Mucosal Melanoma Who Have Previously Received Anti-PD-[L]-1 Therapy - ARTISTRY-6
• Actual Study Start Date: May 27, 2021
• Estimated Primary Completion Date: March 2024
• Estimated Study Completion Date: September 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Advanced Cutaneous Melanoma; Patients with unresectable and/or metastatic cutaneous melanoma	Drug: Nemvaleukin Alfa Subcutaneous; Subcutaneous injection of nemvaleukin every 7 days; Other Name: ALKS 4230 Subcutaneous
Experimental: Advanced mucosal melanoma; Patients with unresectable and/or metastatic mucosal melanoma	Drug: Nemvaleukin Alfa Intravenous; Intravenous (IV) infusion over 30 minutes given daily for 5 consecutive days; Other Name: ALKS 4230 Intravenous

Outcome Measures

Primary Outcome Measures :

1. Centrally-assessed overall response rate (ORR) [ 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

Secondary Outcome Measures :

1. Centrally-assessed duration of response (DOR) [ Time Frame: Assessed up to 2 years from the first dose ]
   -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
2. Centrally-assessed progression free survival (PFS) [ Time Frame: Assessed up to 2 years from the first dose ]
   -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
3. Centrally-assessed disease control rate (DCR) [ Time Frame: Assessed up to 2 years from the first dose ]
   -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
4. Centrally-assessed time to response (TTR) [ Time Frame: Assessed up to 2 years from the first dose ]
   -TTR is defined as the time from patient's first dose of nemvaleukin to the first documentation of complete response or partial response
5. Incidence of treatment-emergent adverse events [ Time Frame: Assessed up to 2 years from the first dose ]
6. Investigator-assessed overall response rate (ORR) [ 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
7. Investigator-assessed duration of response (DOR) [ Time Frame: Assessed up to 2 years from the first dose ]
   -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
8. Investigator-assessed progression free survival (PFS) [ Time Frame: Up to 2 years from the first dose ]
   -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
9. Investigator-assessed disease control rate (DCR) [ Time Frame: Assessed up to 2 years from the first dose ]
   -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
10. Investigator-assessed time to response (TTR) [ Time Frame: Assessed up to 2 years from the first dose ]
    -TTR is defined as the time from patient's first dose of nemvaleukin to the first documentation of complete response or partial response
11. Investigator-assessed immune overall response rate (iORR) [ Time Frame: Assessed up to 2 years from the first dose ]
    -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.
12. Investigator-assessed immune duration of response (iDOR) [ Time Frame: Assessed up to 2 years from the first dose ]
    -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
13. Investigator-assessed immune progression free survival (iPFS) [ Time Frame: Assessed up to 2 years from the first dose ]
    -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
14. Investigator-assessed immune disease control rate (iDCR) [ Time Frame: Assessed up to 2 years from the first dose ]
    -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
15. Investigator-assessed immune time to response (iTTR) [ Time Frame: Assessed up to 2 years from the first dose ]
    -iTTR is defined as the time from patient's first dose of nemvaleukin to the first documentation of complete or partial response

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• The patient must have advanced cutaneous melanoma or acral melanoma; no more than 5 patients with acral melanoma may enroll in this cohort (Cohort 1). Or, the patient must have unresectable and/or metastatic mucosal melanoma (Cohort 2).

• The patient must have received previous treatment as follows:

  1. 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.
  2. 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, 4 doses of pembrolizumab every 3 weeks).
  3. 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.
• Patient has received prior 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, nephritis, and neuropathy).
• Additional criteria may apply.

Contacts and Locations

Contacts

Contact: Senior Director, Global Clinical Services; 888-235-8008 (US Only); clinicaltrials@alkermes.com

Contact: Senior Director, Global Clinical Services; 1-571-599-2702 (Global); clinicaltrials@alkermes.com

Locations

United States, California

Alkermes Investigator Site; Recruiting

Los Angeles, California, United States, 90025

United States, Kentucky

Alkermes Investigator Site; Recruiting

Louisville, Kentucky, United States, 40018

United States, Massachusetts

Alkermes Investigator Site; Recruiting

Boston, Massachusetts, United States, 02114

United States, Minnesota

Alkermes Investigator Site; Recruiting

Saint Paul, Minnesota, United States, 55101

United States, New York

Alkermes Investigator Site; Recruiting

New York, New York, United States, 10016

Alkermes Investigator Site; Recruiting

New York, New York, United States, 10032

Canada, Quebec

Alkermes Investigator Site; Recruiting

Montreal, Quebec, Canada, H2X 1R9

Korea, Republic of

Alkermes Investigator Site; Recruiting

Seoul, Seocho-gu, Korea, Republic of, 03722

Alkermes Investigator Site; Recruiting

Seoul, Seocho-gu, Korea, Republic of, 06591

Alkermes Investigator Site; Recruiting

Gangam-gu, Seoul, Korea, Republic of, 06351

Alkermes Investigator Site; Recruiting

Jongno-gu, Seoul, Korea, Republic of, 03080

Alkermes Investigator Site; Recruiting

Songpa-Gu, Seoul, Korea, Republic of, 05505

Alkermes Investigator Site; Recruiting

Daegu, Korea, Republic of, 41404

Alkermes Investigator Site; Recruiting

Daejeon, Korea, Republic of, 35015

Sponsors and Collaborators

Alkermes, Inc.

Investigators

• Study Director: Carlos Mayo, MD; Alkermes, Inc.

More Information

• Responsible Party: Alkermes, Inc.
• ClinicalTrials.gov Identifier: NCT04830124
• Other Study ID Numbers: ALKS 4230-006
• First Posted: April 2, 2021
• Last Update Posted: January 11, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alkermes, Inc.:

Alkermes; ALKS 4230; Melanoma; Immunotherapy; Nemvaleukin alfa; IL-2; Interlukin-2; Oncology; Cytokine; Nemvaleukin

Additional relevant MeSH terms:

Melanoma; Skin Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases