Cutaneous Melanoma, Mucosal Melanoma
Conditions
Keywords
ALKS 4230, Melanoma, Immunotherapy, Nemvaleukin alfa, IL-2, Interlukin-2, Oncology, Cytokine, Nemvaleukin, Mural Oncology, Pembrolizumab
Brief summary
This study observes the antitumor activity, safety, tolerability, PK, and pharmacodynamics in patients with inoperable and/or metastatic melanoma
Interventions
DRUGNemvaleukin Alfa Subcutaneous
Subcutaneous injection of nemvaleukin every 7 days
DRUGNemvaleukin Alfa Intravenous
Intravenous (IV) infusion over 30 minutes given daily for 5 consecutive days
DRUGNemvaleukin Alfa Intravenous Less Frequent Dosing
Intravenous (IV) infusion over 30 minutes twice every 21 days (Day 1 and Day 8 dosing of a 21 day cycle)
DRUGPembrolizumab
Cohort 4 only: 200mg IV pembrolizumab on Day 1 of a 21-day cycle
Sponsors
Mural Oncology, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. * Cohorts 1 and 2 (required), Cohort 3 (optional), Cohort 4 (may be required, otherwise optional). Patient is willing to undergo a pretreatment tumor biopsy or provide qualifying archival tumor tissue. Cohort 4 - Patients are required to have known tumor PD-\[L\]1 status determined by local testing using an approved assay. PD-\[L\]1 testing performed prior to enrolling on the study is acceptable if there was no intervening systemic anti-cancer therapy, and archival tissue may be used for testing provided the biopsy is ≤3 months old. * 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, 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. * Patients who have previously discontinued immunotherapy due to immune-related adverse event (irAEs) will be excluded. * Cohort 4 only: Patient has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis. * Additional criteria may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Centrally-assessed overall response rate (ORR) (Cohort 1 and 2) | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| Centrally-assessed progression free survival (PFS) (Cohort 1 and 2) | 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 |
| Investigator-assessed progression free survival (PFS) (Cohort 3 and 4) | 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 |
| Centrally-assessed disease control rate (DCR) (Cohort 1 and 2) | 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 |
| Investigator-assessed disease control rate (DCR) (Cohort 3 and 4) | 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 |
| Centrally-assessed time to response (TTR) (Cohort 1 and 2) | 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 |
| Investigator-assessed time to response (TTR) (Cohort 3 and 4) | 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 |
| Centrally-assessed duration of response (DOR) (Cohort 1 and 2) | 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 |
| Investigator-assessed overall response rate (ORR) (Cohort 1 and 2) | 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 |
| Investigator-assessed immune overall response rate (iORR) (All cohorts) | 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. |
| Investigator-assessed immune duration of response (iDOR) (All cohorts) | 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 |
| Investigator-assessed immune progression free survival (iPFS) (All cohorts) | 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 |
| Investigator-assessed immune disease control rate (iDCR) (All cohorts) | 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 |
| Investigator-assessed immune time to response (iTTR) (All cohorts) | 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 |
| Incidence of treatment-emergent adverse events (All cohorts) | 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 | -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 |
Countries
Australia, Canada, Italy, South Korea, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed