Advanced cutaneous melanoma and Advanced mucosal melanoma MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Nemvaleukin Alfa (Formulation 2)
Product Code: [ALKS 4230
RDB-1450]
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Nemvaleukin alfa
CAS Number: 2315268-27-8
Current Sponsor code: ALKS 4230
Concentration unit: mg milligram(s
Sponsors
ALKERMES
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient is =18 years of age. 2. Patient or patient's legal representative is willing and able to provide written informed consent. 3. Patient is willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study. 4. The patient must have one of the following tumor types: • Cohort 1 (advanced cutaneous melanoma cohort): Patient has unresectable and/or metastatic cutaneous melanoma. No more than 5 patients with acral melanoma may enroll in this cohort. • Cohort 2 (advanced mucosal melanoma cohort): Patient has unresectable and/or metastatic mucosal melanoma. 5. The patient must have received previous treatment as follows: a. 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 antineoplastic therapy (eg, targeted therapy, chemotherapy). Previous adjuvant and/or neoadjuvant therapy counts as one prior regimen. b. Patients have experienced objective response (PR or CR; by RECIST 1.1 or iRECIST) or SD (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 a minimum of 12 weeks (eg, 4 doses of pembrolizumab q3w). c. Patients with BRAF mutations may or may not have received prior targeted therapy. 6. 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 ISRs 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. 7. 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 loco-regional therapy, are not considered measurable unless there has been demonstrated progression in the lesion. 8. 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. 9. Patient has recovered from the effects of any previous chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, and/or surgery (ie, 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]). 10. 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. FOR COMPLETE LIST PLEASE REFER TO PROTOCOL Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Numbe
Exclusion criteria
Exclusion criteria: 1. Patient has uveal melanoma. 2. 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. 3. 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). 4. 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. 5. Patient has taken non-steroid systemic immunomodulatory agents (eg, Enbrel®, Humira®, etc) within 28 days prior to the first dose of study drug or anticipates use of these therapies during the study period. 6. Patient has undergone prior solid organ and/or non-autologous hematopoietic stem cell or bone marrow transplant. 7. 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 (see Section 8.4.2 for further details). 8. Patient has received more than 3 doses of therapeutic systemic broadspectrum antibiotics within 4 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. 9. 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. 10. 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. FOR COMPLETE LIST PLEASE REFER TO PROTOCOL
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the antitumor activity of nemvaleukin by centralized reviewers' assessment of ORR separately for patients with: - Advanced cutaneous melanoma (Cohort 1) - Advanced mucosal melanoma (Cohort 2);Secondary Objective: To evaluate the antitumor activity of nemvaleukin (other than by centrally-assessed ORR) separately for patients with: - Advanced cutaneous melanoma (Cohort 1) - Advanced mucosal melanoma (Cohort 2) To evaluate the safety and tolerability of nemvaleukin separately for patients with: - Advanced cutaneous melanoma (Cohort 1) - Advanced mucosal melanoma (Cohort 2);Primary end point(s): Centrally-assessed overall response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;Timepoint(s) of evaluation of this end point: As per RECIST 1.1 Criteria. Cohort 1: Following baseline assessment, tumor assessment is to be performed every 6 weeks (i.e., on even-numbered cycles) for the first year and then every 12 weeks thereafter. Cohort 2: Following baseline assessment, tumor assessment is to be performed anytime after dosing on C3D5 but prior to dosing on C4D1 (8 weeks), then every 6 weeks for the remainder of the first year, and then every 12 weeks thereafter. Cohort 1 and 2: A confirmatory scan for the first demonstration of a partial response (PR) or better should be performed at no sooner than 4 weeks and no later than 6 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints: - Centrally-assessed duration of response (DOR), progression-free survival (PFS), and disease control rate (DCR), and time to response (TTR) based on RECIST 1.1. - Safety and tolerability will be assessed on the basis of treatment emergent adverse events (TEAEs), vital signs and weight, electrocardiograms (ECGs), and clinical laboratory parameters. Other Secondary Endpoints: - Investigator-assessed ORR, DOR, PFS, DCR, and TTR based on RECIST 1.1 - Investigator-assessed immune ORR (iORR), immune DOR (iDOR), immune PFS (iPFS), immune;Timepoint(s) of evaluation of this end point: As described in Schedule of assessments in the protocol. | — |
Countries
Australia, Canada, Hong Kong, Italy, Korea, Republic of, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactJames Corkery
Alkermes Inc
Outcome results
None listed