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


About this study

The purpose of this study is to observe the antitumor activity, safety, tolerability, PK, and pharmacodynamics in patients with inoperable and/or metastatic melanoma following prior anti-PD-[L]-1 therapy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Patient is ≥ 18 years of age.
  • Patient or patient’s legal representative is willing and able to provide written informed consent.
  • Patient is willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
  • 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).
  • Patient must have received previous treatment as follows:
    • patient has received anti-PD-[L]1 therapy ± anti-CTLA-4 therapy, and ≤ 1 other prior regimen of systemic anti-neoplastic therapy;
    • patient should have experienced objective response (PR or CR) or SD as BOR to anti-PD-[L]1 therapy;
    • patients with BRAF mutations may or may not have received prior targeted therapy.
  • A patient who has received prior treatment with talimogene laherparepvec (TVEC) is 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.
  • Patient has at least one measurable lesion that qualifies as a target lesion based on RECIST 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other locoregional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
  • Patient is willing to undergo a pretreatment tumor biopsy or provide qualifying archival tumor tissue. To qualify, archival tissue must have been sampled after last exposure to any systemic anti-neoplastic agent (including TVEC). Patients unable to undergo a biopsy may be enrolled if risk/benefit ratio of biopsy is considered unfavorable and/or when a biopsy would likely lead to significant delays in care. This decision must be accompanied by supporting documentation from the Investigator and performed in consultation with Medical Monitor. All pretreatment tissue must have been collected no more than 120 days prior to screening.
  • Patient has recovered from the effects of any previous chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, and/or surgery (i.e., residual toxicity no worse than Grade 1 [Grade 2 treatment-associated peripheral neuropathy and/or any grade of alopecia are acceptable assuming all other inclusion criteria are met]).
  • Patient who has received prior systemic anti-neoplastic agent(s) must wait at least 5 half-lives or 4 weeks (whichever is shorter) following prior therapy before enrollment into the study, or 4 weeks if the half-life of a given investigational agent is not known.
  • Patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 5 days before the first dose of study drug and an estimated life expectancy of at least 3 months.
  • Patient has adequate hematologic reserve as evidenced by:
    • Absolute neutrophil count (ANC) of ≥ 1000/µL;
    • Absolute lymphocyte count of ≥ 500/µL;
    • Platelet count of ≥ 75,000/µL; and
    • Hemoglobin of ≥ 9 g/dL (patients may be transfused to this level if necessary, but transfusion must occur > 1 week prior to the first dose of study drug).
  • Patient has adequate hepatic function as evidenced by aspartate transaminase and alanine transaminase values ≤ 3 × the upper limit of normal (ULN) and serum total bilirubin values of ≤ 1.5 × ULN (≤ 2 × ULN for patients with known Gilbert’s syndrome) for the reference laboratory measured within 7 days prior to the first dose of study drug. For patients with documented baseline liver metastasis, the following limits will apply: 5 × ULN for transaminase and 2 × ULN for bilirubin.
  • Patient has adequate renal function as evidenced by a serum creatinine ≤ 1.5 × the ULN for the reference laboratory or a calculated creatinine clearance of ≥ 45 mL/min by the Cockcroft-Gault Equation measured within 7 days prior to the first dose of study drug.
  • Patient has international normalized ratio (INR) AND/OR prothrombin time (PT) AND activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless the patient is receiving anticoagulant therapy, in which case INR and/or PT and aPTT must be within the desired therapeutic range of intended use for such anticoagulants.
  • Patient agrees to abide by the contraceptive requirements detailed in the protocol.
  • Women of childbearing potential (WOCBP) must have a negative pregnancy test (serum or urine) within 3 days before the first dose of study drug (see the protocol for the definition of WOCBP).

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 has received radiotherapy within the last 4 weeks before start of study treatment, with the exception of limited field palliative radiotherapy to an area not inclusive of or adjacent to the target lesion(s), that has been completed at least 2 weeks before starting study treatment with no ongoing acute sequelae (eg, radiation burns).
  • Patient requires systemic corticosteroids (> 10 mg of prednisone daily, or equivalent) or patient has taken systemic corticosteroids (> 10 mg of prednisone daily, or equivalent) within 14 days prior to the first dose of study drug; however, replacement doses, topical, ophthalmologic, and inhalational steroids are permitted.
  • Patient has taken non-steroid systemic immunomodulatory agents (e.g., Enbrel®, Humira®, etc) within 28 days prior to the first dose of study drug or anticipates use of these therapies during the study period.
  • Patient has undergone prior solid organ and/or non-autologous hematopoietic stem cell or bone marrow transplant.
  • Patient has received a live or live-attenuated vaccine(s) within 30 days prior to the first dose of study treatment.
    • Note: COVID-19 vaccine is allowed.
  • Patient has received more than 3 doses of therapeutic systemic broad-spectrum antibiotics within 14 days prior to the first dose of study drug. Antibiotics given for peri-procedural prophylaxis or given presumptively for a limited time (eg, until infection was ruled out), as well as topical or intra-ocular antibiotics, shall not be exclusionary.
  • Patient has had any active infection and/or a fever ≥ 38.5°C (≥ 101°F) within 3 days prior to the first dose of study drug.
  • Patient has active autoimmune disease(s) requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease that has required chronic or frequent systemic steroids. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed.
  • Patient has underlying chronic lung disease, chronic obstructive pulmonary disease, metastatic lung disease, pleural effusions or other lung disorders (eg, pulmonary embolism) with a baseline room air oxygen saturation of < 92% at screening, and/or dyspnea (≥ Grade 3), which requires oxygen therapy.
  • Patient has any other concurrent uncontrolled illness, including mental illness or substance use, which may interfere with the ability of the patient to cooperate and participate in the study. Other examples of such conditions would include unstable, poorly controlled, or severe hypertension; clinically significant pericardial effusion; New York Heart Association Class III or Class IV congestive heart failure; high risk cardiovascular disease, defined as unstable angina, myocardial infarction, or cerebrovascular accident within 6 months of first dose; uncontrolled diabetes mellitus that has required 2 or more hospitalizations in the last year and/or emergent management within the last 6 months; severe peripheral vascular disease; or recent serious trauma.
  • Patient has had an active second malignancy within the previous 2 years. This criterion does not apply to patients with adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, prostate cancer of highest Gleason score ≤ 6 with undetectable prostate-specific antigen over the previous 12 months, urothelial carcinoma in situ, or ductal carcinoma in situ of the breast that has undergone full surgical resection.
  • 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.
  • Patient has active or symptomatic central nervous system metastases unless all the following have been met: such metastases have been treated by surgery and/or radiation therapy, and/or gamma knife and have remained radiographically stable (or shrinking) on 2 consecutive imaging examinations performed at least 6 weeks apart; AND steroids have been tapered to a dose of 10 mg of prednisone (or equivalent) or less for at least 2 weeks prior to first dose of study agent(s); AND the patient is neurologically stable. Patients with history of brain metastases or a suspicion of brain metastases must have a brain magnetic resonance imaging (MRI) at baseline (Screening Visit).
  • Patient has known or suspected hypersensitivity to any components of nemvaleukin.
  • Patient has active uncontrolled coagulopathy.
  • 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 is known to be positive for human immunodeficiency virus. Patients with known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) are excluded; however, a patient with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) may be enrolled provided that HBV DNA is negative. Patients with known active hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] are detected) are excluded, however, a patient with cured hepatitis C (negative HCV RNA status) may be enrolled.
  • Patient has active or latent tuberculosis. Patients with cured tuberculosis may be enrolled.
  • Patient has developed Grade ≥ 3 immune-related adverse events (irAEs) while on prior immunotherapy (e.g., pneumonitis, nephritis, and neuropathy). Patients who have immunerelated endocrinopathies and are stable on hormone replacement therapy are not excluded. Patients who experienced colitis as a toxicity of prior immunotherapy must have undergone colonoscopy since last symptoms of colitis that confirms the absence of ongoing inflammation. Vitiligo is not exclusionary.

Eligibility last updated 9/24/21. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Roxana Dronca, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Matthew Block, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


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Cancer-related trials contact form

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