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The study will be conducted in 2 cohorts. A single-center design for the tumor microenvironment (TME) cohort (Cohort 1), and a multicenter design for the less frequent intravenous (IV) dosing cohort (Cohort 2).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Tumor Microenvironment (TME) Nemvaleukin and Pembrolizumab | Experimental | Nemvaleukin will be administered via Intravenous (IV) infusion given daily for 5 consecutive days followed by an off-treatment period. Starting on Cycle 3, Day 1 of each cycle, Pembrolizumab will be administered via IV infusion followed by IV infusion of nemvaleukin |
|
| Cohort 2 Part A: Less Frequent IV Dosing Nemvaleukin | Experimental |
| |
| Cohort 2 Part B: Less Frequent IV Dosing Nemvaleukin and Pembrolizumab | Experimental | This arm will not open for enrollment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nemvaleukin alfa | Biological | IV infusion over 30 minutes |
|
| Measure | Description | Time Frame |
|---|---|---|
| Changes in density (cell counts per mm2) of immune cell (including total T cells, CD8+ T cells, CD56+ cells and Treg cells) | Changes in density (cell counts per mm2) of immune cell (including total T cells, CD8+ T cells, CD56+ cells and Treg cells) based on immunohistochemistry (IHC) and/or immunofluorescence (IF) in the TME between pretreatment and on-treatment (Cycle 2 Day 8) paired tumor biopsies | From the time of the Patient's pre-treatment biopsy to the time of the Patient's on-treatment biopsy |
| Changes in ratios (including T/Treg, CD8+/Treg, CD56+/Treg) based on immunohistochemistry (IHC) and/or immunofluorescence (IF) in the TME between pretreatment and on-treatment (Cycle 2 Day 8) paired tumor biopsies | From the time of the Patient's pre-treatment biopsy to the time of the Patient's on-treatment biopsy | |
| Incidence of dose-limiting toxicity (DLT) | From the first dose through end of dose-limiting toxicity observation period (up to 24 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of subjects with objective evidence of Complete or Partial Response [(CR)/immune CR (iCR) or (PR) immune PR (iPR)](CR)/immune CR (iCR) | From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months | |
| Duration of response in subjects with Complete or Partial Response [(CR)/immune CR (iCR) or (PR) immune PR (iPR)] |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Mural Oncology | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| START Midwest | Grand Rapids | Michigan | 49546 | United States | ||
| MD Anderson Cancer Center |
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|
| Pembrolizumab | Biological | IV infusion over 30 minutes |
|
|
| Time from the first documentation of complete response or partial response to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months) |
| Incidence of Adverse Events | Time from first dose of study drug to the end of study (estimated up to 24 months) |
| Incidence of drug-related Serious Adverse Events | Time from first dose of study drug to the end of study (estimated up to 24 months) |
| Incidence of drug-related Adverse Events leading to discontinuation | Time from first dose of study drug to the end of study (estimated up to 24 months) |
| Serum concentrations of ALKS 4230 | Concentration data will be summarized by dose level | From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months |
| Serum will be assayed for the presence of anti-ALKS 4230 antibodies | Results will be summarized by dose level | From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months |
| Changes in absolute cell numbers (including total T cells, CD8+ T cells, NK cells and Treg cells) | Changes in absolute cell numbers (including total T cells, CD8+ T cells, NK cells and Treg cells) between pretreatment and on-treatment serial peripheral blood samples obtained from patients being treated with ALKS 4230 monotherapy and with the combination of ALKS 4230 plus pembrolizumab | From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months |
| Changes in ratios (including T/Treg, CD8+/Treg, NK/Treg) between pretreatment and on treatment | Changes in ratios (including T/Treg, CD8+/Treg, NK/Treg) between pretreatment and on-treatment serial peripheral blood samples obtained from patients being treated with ALKS 4230 monotherapy and with the combination of ALKS 4230 plus pembrolizumab | From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months |
| Serum concentrations of proinflammatory cytokines, including IFNγ, TNF-α, IL-1B, IL-6, IL-10, will be assessed using a multiplex method from initiation of therapy | From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months |
| Changes in absolute numbers of circulating leukocytes | Changes in absolute numbers of circulating leukocytes between pretreatment and on-treatment serial peripheral blood samples obtained from patients being treated with ALKS 4230 monotherapy and with the combination of ALKS 4230 plus pembrolizumab | From time of initiation of therapy until the last treatment cycle (each cycle is 14 or 21 days), assessed up to 24 months |
| Houston |
| Texas |
| 77030 |
| United States |
| START Mountain | West Valley City | Utah | 84119 | United States |
| NEXT Virginia | Fairfax | Virginia | 22031 | United States |
| Hospital Clinico San Carlos | Madrid | 28040 | Spain |
| CIOCC HM Sanchinarro | Madrid | 28050 | Spain |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jun 30, 2025 | Jul 17, 2025 | 8 | ||
| Aug 11, 2025 | Aug 28, 2025 | 9 |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
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